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The Biology of ‘Precancer’: Stopping Cancer Before It Starts
Some breast cancer types are more likely than others to recur. Researchers have known this for more than a decade.
But they have long wondered why.
“How did those tumor types arise?” said Christina Curtis, PhD, a professor of medicine, genetics and biomedical data science at Stanford University in California. “They’re all breast cancers. They’re all estrogen receptor positive. But these groups are different. When did they become different, and how is that determined?”
Dr. Curtis and colleagues are finally starting to answer these questions. They recently broke new ground in a study linking differences in cancer-related genes to disease subtype and aggressiveness.
DNA inherited from our parents is known as the germline genome. It affects whether the immune system attacks or retreats when confronted with variations that may lead to breast cancer.
“It turns out, the germline genome sculpts tumor evolution,” said Dr. Curtis.
The study is part of a growing effort to understand “precancer” — the critical period after cells have started to grow abnormally but before they’ve developed into cancer — a research trend that could trigger a decisive shift in how cancer treatments are realized. Therapeutics could be designed on the basis of the biology of these precancerous cells.
While biotech start-ups push new tests to catch cancer early, researchers like Dr. Curtis hope to stop cancer before it even starts.
“This is a really exciting area of research,” said Susan Domchek, MD, executive director of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, who was not involved in the study. “What we hope for is that, over time, we’re going to have more and more biologically driven interception.”
‘We’re Basically Unearthing the Dark Matter of the Human Genome’
Of course, we already have mechanical ways of heading off cancer, like having a precancerous polyp removed. But for the Stanford researchers, biologic interception is the goal. They hope to figure out how to use the immune system to stop the cancer.
In their study, they looked at DNA variabilities known as somatic aberrations or single-nucleotide protein sequences (SNPs). The HER2 gene, for example, can contain SNPs — possibly affecting how the HER2 protein regulates breast cell growth and division.
“There’s been a huge effort through genomewide association studies to link SNPs to cancer outcomes and risk,” Dr. Curtis said.
Focusing on people with a genetic predisposition for breast cancer, Dr. Curtis used machine learning to show that these variabilities can occur in specific epitopes (protein features that can trigger an immune response).
They also found that heightened variability can show up in a region of the genome called the human leukocyte antigen (HLA). Each HLA molecule can contain many epitopes.
“We developed a whole new algorithm to compute this ‘germline epitope burden,’ ” Dr. Curtis said. “We’re basically unearthing the dark matter of the human genome to ask about the interplay between SNPs and HLA class one presentation.”
These aberration-rich regions can grab the immune system’s attention. Sometimes the immune system identifies and eradicates those epitopes.
In that case: “I have immunosurveillance. I’ve cured my cancer,” said Nora Disis, PhD, director of the Cancer Vaccine Institute and a professor of medicine at the University of Washington, Seattle. Dr. Disis was not involved in the study.
But other times, the immune system finds a way around the high “epitope burden,” and the tumors become more aggressive and immunosuppressive. That’s when cancer forms.
This suggests a “critical juncture between preinvasive and invasive disease,” Dr. Curtis said.
And that “critical juncture” may very well be the optimal time for intervention.
The Precancer Push
Stanford’s findings add information to prior biomarkers and may provide a way to identify “bad-acting tumors” from a simple blood draw measuring germline epitope burden, Dr. Curtis said. Looking further ahead, “this also reveals a new source of epitopes that might be immunogenic and might be informative for the development of vaccines.”
Many labs are trying to understand the biology of precancer and exploring possible vaccines.
The National Cancer Institute’s Human Tumor Atlas Network is building three-dimensional models of the evolution from precancerous to advanced disease. And researchers at the Cancer Vaccine Institute at the University of Washington are developing a vaccine for a precancerous lesion linked to many ovarian cancers.
Dr. Domchek’s research explores whether breast cancers caused by mutations in the BRCA 1 and 2 genes can be intercepted at very early stages. In a clinical trial of healthy people with those mutations, Dr. Domchek and colleagues are attempting to “rev up the immune system to tackle telomerase,” an enzyme that’s over-expressed in 95% of cancers. The hope is for this experimental vaccine to lower their risk of developing cancer.
At the Fred Hutch Cancer Center, Seattle, Ming Yu, PhD, is studying how senescent cells affect immune cells in precancer. As cells age and stop dividing, she said, they can accumulate and create a “tumor-promoting microenvironment” in older people.
Dr. Yu has found that the antiaging drug rapamycin can eliminate those “zombie cells” in mice. She’s studying whether the “cleanup” can help prevent cancer and expects results in a few months.
In the years and decades to come, all of this could lead to a new era in cancer treatment.
“Most drug development starts with people with advanced cancer and then goes into the earlier and earlier spaces,” said Dr. Domchek. “But it may be that we’re thinking about it all wrong and that you really have to understand the unique biology of early lesions to go after them.”
A version of this article first appeared on Medscape.com.
Some breast cancer types are more likely than others to recur. Researchers have known this for more than a decade.
But they have long wondered why.
“How did those tumor types arise?” said Christina Curtis, PhD, a professor of medicine, genetics and biomedical data science at Stanford University in California. “They’re all breast cancers. They’re all estrogen receptor positive. But these groups are different. When did they become different, and how is that determined?”
Dr. Curtis and colleagues are finally starting to answer these questions. They recently broke new ground in a study linking differences in cancer-related genes to disease subtype and aggressiveness.
DNA inherited from our parents is known as the germline genome. It affects whether the immune system attacks or retreats when confronted with variations that may lead to breast cancer.
“It turns out, the germline genome sculpts tumor evolution,” said Dr. Curtis.
The study is part of a growing effort to understand “precancer” — the critical period after cells have started to grow abnormally but before they’ve developed into cancer — a research trend that could trigger a decisive shift in how cancer treatments are realized. Therapeutics could be designed on the basis of the biology of these precancerous cells.
While biotech start-ups push new tests to catch cancer early, researchers like Dr. Curtis hope to stop cancer before it even starts.
“This is a really exciting area of research,” said Susan Domchek, MD, executive director of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, who was not involved in the study. “What we hope for is that, over time, we’re going to have more and more biologically driven interception.”
‘We’re Basically Unearthing the Dark Matter of the Human Genome’
Of course, we already have mechanical ways of heading off cancer, like having a precancerous polyp removed. But for the Stanford researchers, biologic interception is the goal. They hope to figure out how to use the immune system to stop the cancer.
In their study, they looked at DNA variabilities known as somatic aberrations or single-nucleotide protein sequences (SNPs). The HER2 gene, for example, can contain SNPs — possibly affecting how the HER2 protein regulates breast cell growth and division.
“There’s been a huge effort through genomewide association studies to link SNPs to cancer outcomes and risk,” Dr. Curtis said.
Focusing on people with a genetic predisposition for breast cancer, Dr. Curtis used machine learning to show that these variabilities can occur in specific epitopes (protein features that can trigger an immune response).
They also found that heightened variability can show up in a region of the genome called the human leukocyte antigen (HLA). Each HLA molecule can contain many epitopes.
“We developed a whole new algorithm to compute this ‘germline epitope burden,’ ” Dr. Curtis said. “We’re basically unearthing the dark matter of the human genome to ask about the interplay between SNPs and HLA class one presentation.”
These aberration-rich regions can grab the immune system’s attention. Sometimes the immune system identifies and eradicates those epitopes.
In that case: “I have immunosurveillance. I’ve cured my cancer,” said Nora Disis, PhD, director of the Cancer Vaccine Institute and a professor of medicine at the University of Washington, Seattle. Dr. Disis was not involved in the study.
But other times, the immune system finds a way around the high “epitope burden,” and the tumors become more aggressive and immunosuppressive. That’s when cancer forms.
This suggests a “critical juncture between preinvasive and invasive disease,” Dr. Curtis said.
And that “critical juncture” may very well be the optimal time for intervention.
The Precancer Push
Stanford’s findings add information to prior biomarkers and may provide a way to identify “bad-acting tumors” from a simple blood draw measuring germline epitope burden, Dr. Curtis said. Looking further ahead, “this also reveals a new source of epitopes that might be immunogenic and might be informative for the development of vaccines.”
Many labs are trying to understand the biology of precancer and exploring possible vaccines.
The National Cancer Institute’s Human Tumor Atlas Network is building three-dimensional models of the evolution from precancerous to advanced disease. And researchers at the Cancer Vaccine Institute at the University of Washington are developing a vaccine for a precancerous lesion linked to many ovarian cancers.
Dr. Domchek’s research explores whether breast cancers caused by mutations in the BRCA 1 and 2 genes can be intercepted at very early stages. In a clinical trial of healthy people with those mutations, Dr. Domchek and colleagues are attempting to “rev up the immune system to tackle telomerase,” an enzyme that’s over-expressed in 95% of cancers. The hope is for this experimental vaccine to lower their risk of developing cancer.
At the Fred Hutch Cancer Center, Seattle, Ming Yu, PhD, is studying how senescent cells affect immune cells in precancer. As cells age and stop dividing, she said, they can accumulate and create a “tumor-promoting microenvironment” in older people.
Dr. Yu has found that the antiaging drug rapamycin can eliminate those “zombie cells” in mice. She’s studying whether the “cleanup” can help prevent cancer and expects results in a few months.
In the years and decades to come, all of this could lead to a new era in cancer treatment.
“Most drug development starts with people with advanced cancer and then goes into the earlier and earlier spaces,” said Dr. Domchek. “But it may be that we’re thinking about it all wrong and that you really have to understand the unique biology of early lesions to go after them.”
A version of this article first appeared on Medscape.com.
Some breast cancer types are more likely than others to recur. Researchers have known this for more than a decade.
But they have long wondered why.
“How did those tumor types arise?” said Christina Curtis, PhD, a professor of medicine, genetics and biomedical data science at Stanford University in California. “They’re all breast cancers. They’re all estrogen receptor positive. But these groups are different. When did they become different, and how is that determined?”
Dr. Curtis and colleagues are finally starting to answer these questions. They recently broke new ground in a study linking differences in cancer-related genes to disease subtype and aggressiveness.
DNA inherited from our parents is known as the germline genome. It affects whether the immune system attacks or retreats when confronted with variations that may lead to breast cancer.
“It turns out, the germline genome sculpts tumor evolution,” said Dr. Curtis.
The study is part of a growing effort to understand “precancer” — the critical period after cells have started to grow abnormally but before they’ve developed into cancer — a research trend that could trigger a decisive shift in how cancer treatments are realized. Therapeutics could be designed on the basis of the biology of these precancerous cells.
While biotech start-ups push new tests to catch cancer early, researchers like Dr. Curtis hope to stop cancer before it even starts.
“This is a really exciting area of research,” said Susan Domchek, MD, executive director of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, who was not involved in the study. “What we hope for is that, over time, we’re going to have more and more biologically driven interception.”
‘We’re Basically Unearthing the Dark Matter of the Human Genome’
Of course, we already have mechanical ways of heading off cancer, like having a precancerous polyp removed. But for the Stanford researchers, biologic interception is the goal. They hope to figure out how to use the immune system to stop the cancer.
In their study, they looked at DNA variabilities known as somatic aberrations or single-nucleotide protein sequences (SNPs). The HER2 gene, for example, can contain SNPs — possibly affecting how the HER2 protein regulates breast cell growth and division.
“There’s been a huge effort through genomewide association studies to link SNPs to cancer outcomes and risk,” Dr. Curtis said.
Focusing on people with a genetic predisposition for breast cancer, Dr. Curtis used machine learning to show that these variabilities can occur in specific epitopes (protein features that can trigger an immune response).
They also found that heightened variability can show up in a region of the genome called the human leukocyte antigen (HLA). Each HLA molecule can contain many epitopes.
“We developed a whole new algorithm to compute this ‘germline epitope burden,’ ” Dr. Curtis said. “We’re basically unearthing the dark matter of the human genome to ask about the interplay between SNPs and HLA class one presentation.”
These aberration-rich regions can grab the immune system’s attention. Sometimes the immune system identifies and eradicates those epitopes.
In that case: “I have immunosurveillance. I’ve cured my cancer,” said Nora Disis, PhD, director of the Cancer Vaccine Institute and a professor of medicine at the University of Washington, Seattle. Dr. Disis was not involved in the study.
But other times, the immune system finds a way around the high “epitope burden,” and the tumors become more aggressive and immunosuppressive. That’s when cancer forms.
This suggests a “critical juncture between preinvasive and invasive disease,” Dr. Curtis said.
And that “critical juncture” may very well be the optimal time for intervention.
The Precancer Push
Stanford’s findings add information to prior biomarkers and may provide a way to identify “bad-acting tumors” from a simple blood draw measuring germline epitope burden, Dr. Curtis said. Looking further ahead, “this also reveals a new source of epitopes that might be immunogenic and might be informative for the development of vaccines.”
Many labs are trying to understand the biology of precancer and exploring possible vaccines.
The National Cancer Institute’s Human Tumor Atlas Network is building three-dimensional models of the evolution from precancerous to advanced disease. And researchers at the Cancer Vaccine Institute at the University of Washington are developing a vaccine for a precancerous lesion linked to many ovarian cancers.
Dr. Domchek’s research explores whether breast cancers caused by mutations in the BRCA 1 and 2 genes can be intercepted at very early stages. In a clinical trial of healthy people with those mutations, Dr. Domchek and colleagues are attempting to “rev up the immune system to tackle telomerase,” an enzyme that’s over-expressed in 95% of cancers. The hope is for this experimental vaccine to lower their risk of developing cancer.
At the Fred Hutch Cancer Center, Seattle, Ming Yu, PhD, is studying how senescent cells affect immune cells in precancer. As cells age and stop dividing, she said, they can accumulate and create a “tumor-promoting microenvironment” in older people.
Dr. Yu has found that the antiaging drug rapamycin can eliminate those “zombie cells” in mice. She’s studying whether the “cleanup” can help prevent cancer and expects results in a few months.
In the years and decades to come, all of this could lead to a new era in cancer treatment.
“Most drug development starts with people with advanced cancer and then goes into the earlier and earlier spaces,” said Dr. Domchek. “But it may be that we’re thinking about it all wrong and that you really have to understand the unique biology of early lesions to go after them.”
A version of this article first appeared on Medscape.com.
New Gel Makes Alcohol 50% Less Toxic, Curbs Organ Damage
It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.
But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.
“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.
The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.
“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.”
Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.
“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.
Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.
Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.
“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.
Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
Bypassing a Problematic Pathway
A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.
“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.
To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.
A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
What’s Next?
With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.
An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
A version of this article appeared on Medscape.com.
It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.
But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.
“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.
The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.
“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.”
Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.
“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.
Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.
Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.
“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.
Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
Bypassing a Problematic Pathway
A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.
“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.
To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.
A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
What’s Next?
With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.
An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
A version of this article appeared on Medscape.com.
It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.
But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.
“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.
The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.
“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.”
Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.
“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.
Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.
Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.
“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.
Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
Bypassing a Problematic Pathway
A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.
“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.
To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.
A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
What’s Next?
With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.
An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
A version of this article appeared on Medscape.com.
Promising New Wearable Could Retrain the Brain After Stroke
A new and deceptively simple advance in chronic stroke treatment could be a vibrating glove.
Researchers at Stanford University and Georgia Tech have developed a wearable device that straps around the wrist and hand, delivering subtle vibrations (akin to a vibrating cellphone) that may relieve spasticity as well as or better than the standard Botox injections.
“The vibro-tactile stimulation can be used at home, and we’re hoping it can be relatively low cost,” said senior study author Allison Okamura, PhD, a mechanical engineer at Stanford University, Stanford, California.
For now, the device is available only to clinical trial patients. But the researchers hope to get the glove into — or rather onto — more patients’ hands within a few years. A recent grant from the National Science Foundation’s Convergence Accelerator program could help pave the way to a commercial product. The team also hopes to expand access in the meantime through larger clinical trials with patients in additional locations.
The work builds on accumulating research exploring vibration and other stimulation therapies as treatments for neurological conditions. Other vibrating gloves have helped reduce involuntary movement for patients with Parkinson’s. And the University of Kansas Medical Center, Kansas City, will soon trial the Food and Drug Administration–approved vagal nerve stimulator, an implantable device intended to treat motor function in stroke survivors. Dr. Okamura noted that devices use “different types of vibration patterns and intensities,” depending on the disease state they target.
Spasticity often develops or worsens months after a stroke. By then, patients may have run out of insurance coverage for rehabilitation. And the effectiveness of Botox injections can “wear out over time,” Dr. Okamura said.
In a clinical trial, patients wore the device for 3 hours a day for 8 weeks, while doing their usual activities. The researchers continued testing their spasticity for 2 more weeks.
How Vibro-Tactile Stimulation May Rewire the Brain
The device originated at Georgia Tech, where Dr. Okamura’s postdoctoral research fellow Caitlyn Seim, PhD, was using vibro-tactile stimulation (VTS) to teach people skills, such as playing the piano, using touch-feedback training. The team decided to target spasticity, which VTS had helped in previousstudies of in-clinic (non-wearable) devices.
How does the device work? The researchers point to neuroplasticity, the ability of neurons to create new synapses or strengthen existing ones in the brain.
“The stimulation is sending additional sensory signals to the brain, which helps the brain interpret and reconnect any lost circuits,” Dr. Okamura said.
Spasticity is driven by “an imbalance in the excitatory drive to the muscles,” she continued. This can lead to worsening contractions, until a hand closes into a fist or a foot curls up. (The team has also done preliminary research on a similar device for foot spasticity, which they hope to continue developing.) Previous studies by Okamura and others suggest that vibration stimulation may prevent these contractions, both in the short and long term.
“Immediately, we do see some softening of the muscles,” Dr. Okamura said. “But in our longer-term study, where we compared to Botox, I also think that the vibration may be retraining the brain to send inhibitory signals. And that can restore balance that’s lost due to the damaged neural circuits from a stroke.”
When the team did a separate study comparing the effects of muscle and skin stimulation, they hypothesized that the vibration could be having a biomechanical effect on the muscle. Instead, they found that stimulating the skin had a greater impact — a “somewhat unexpected” result, Dr. Okamura said. That led them to the brain.
“Stimulating the skin is really about creating sensory signals that get sent to the brain,” Dr. Okamura said, “which is why we think it’s actually a brain-retraining effect and not a direct biomechanical effect.”
What’s Next?
The researchers are seeking funding for longer-term clinical studies to find out if effects persist beyond 2 weeks. They also want to explore how long and often patients should wear the glove for best results.
The researchers also want to study how movement might enhance the effects of the device.
“One of the treatments for spasticity — medications aside, this vibration machine aside — is more exercise, more passive range of motion,” said Oluwole O. Awosika, MD, associate professor at the University of Cincinnati College of Medicine, who was not involved in the study. “It would have been nice to have a control group that didn’t get any of this stimulation or that was only encouraged to do 3 hours of movement a day. What would the difference be?”
Dr. Awosika also wondered how easy it would be for stroke patients without in-home assistance to use the device. “Sometimes wearing these devices requires someone to put it on,” he said.
Of course, if all goes well, patients wouldn’t have to deal with that forever. “The dream would be that you reach true rehabilitation, which is no longer needing the device,” Dr. Okamura said.
A version of this article appeared on Medscape.com.
A new and deceptively simple advance in chronic stroke treatment could be a vibrating glove.
Researchers at Stanford University and Georgia Tech have developed a wearable device that straps around the wrist and hand, delivering subtle vibrations (akin to a vibrating cellphone) that may relieve spasticity as well as or better than the standard Botox injections.
“The vibro-tactile stimulation can be used at home, and we’re hoping it can be relatively low cost,” said senior study author Allison Okamura, PhD, a mechanical engineer at Stanford University, Stanford, California.
For now, the device is available only to clinical trial patients. But the researchers hope to get the glove into — or rather onto — more patients’ hands within a few years. A recent grant from the National Science Foundation’s Convergence Accelerator program could help pave the way to a commercial product. The team also hopes to expand access in the meantime through larger clinical trials with patients in additional locations.
The work builds on accumulating research exploring vibration and other stimulation therapies as treatments for neurological conditions. Other vibrating gloves have helped reduce involuntary movement for patients with Parkinson’s. And the University of Kansas Medical Center, Kansas City, will soon trial the Food and Drug Administration–approved vagal nerve stimulator, an implantable device intended to treat motor function in stroke survivors. Dr. Okamura noted that devices use “different types of vibration patterns and intensities,” depending on the disease state they target.
Spasticity often develops or worsens months after a stroke. By then, patients may have run out of insurance coverage for rehabilitation. And the effectiveness of Botox injections can “wear out over time,” Dr. Okamura said.
In a clinical trial, patients wore the device for 3 hours a day for 8 weeks, while doing their usual activities. The researchers continued testing their spasticity for 2 more weeks.
How Vibro-Tactile Stimulation May Rewire the Brain
The device originated at Georgia Tech, where Dr. Okamura’s postdoctoral research fellow Caitlyn Seim, PhD, was using vibro-tactile stimulation (VTS) to teach people skills, such as playing the piano, using touch-feedback training. The team decided to target spasticity, which VTS had helped in previousstudies of in-clinic (non-wearable) devices.
How does the device work? The researchers point to neuroplasticity, the ability of neurons to create new synapses or strengthen existing ones in the brain.
“The stimulation is sending additional sensory signals to the brain, which helps the brain interpret and reconnect any lost circuits,” Dr. Okamura said.
Spasticity is driven by “an imbalance in the excitatory drive to the muscles,” she continued. This can lead to worsening contractions, until a hand closes into a fist or a foot curls up. (The team has also done preliminary research on a similar device for foot spasticity, which they hope to continue developing.) Previous studies by Okamura and others suggest that vibration stimulation may prevent these contractions, both in the short and long term.
“Immediately, we do see some softening of the muscles,” Dr. Okamura said. “But in our longer-term study, where we compared to Botox, I also think that the vibration may be retraining the brain to send inhibitory signals. And that can restore balance that’s lost due to the damaged neural circuits from a stroke.”
When the team did a separate study comparing the effects of muscle and skin stimulation, they hypothesized that the vibration could be having a biomechanical effect on the muscle. Instead, they found that stimulating the skin had a greater impact — a “somewhat unexpected” result, Dr. Okamura said. That led them to the brain.
“Stimulating the skin is really about creating sensory signals that get sent to the brain,” Dr. Okamura said, “which is why we think it’s actually a brain-retraining effect and not a direct biomechanical effect.”
What’s Next?
The researchers are seeking funding for longer-term clinical studies to find out if effects persist beyond 2 weeks. They also want to explore how long and often patients should wear the glove for best results.
The researchers also want to study how movement might enhance the effects of the device.
“One of the treatments for spasticity — medications aside, this vibration machine aside — is more exercise, more passive range of motion,” said Oluwole O. Awosika, MD, associate professor at the University of Cincinnati College of Medicine, who was not involved in the study. “It would have been nice to have a control group that didn’t get any of this stimulation or that was only encouraged to do 3 hours of movement a day. What would the difference be?”
Dr. Awosika also wondered how easy it would be for stroke patients without in-home assistance to use the device. “Sometimes wearing these devices requires someone to put it on,” he said.
Of course, if all goes well, patients wouldn’t have to deal with that forever. “The dream would be that you reach true rehabilitation, which is no longer needing the device,” Dr. Okamura said.
A version of this article appeared on Medscape.com.
A new and deceptively simple advance in chronic stroke treatment could be a vibrating glove.
Researchers at Stanford University and Georgia Tech have developed a wearable device that straps around the wrist and hand, delivering subtle vibrations (akin to a vibrating cellphone) that may relieve spasticity as well as or better than the standard Botox injections.
“The vibro-tactile stimulation can be used at home, and we’re hoping it can be relatively low cost,” said senior study author Allison Okamura, PhD, a mechanical engineer at Stanford University, Stanford, California.
For now, the device is available only to clinical trial patients. But the researchers hope to get the glove into — or rather onto — more patients’ hands within a few years. A recent grant from the National Science Foundation’s Convergence Accelerator program could help pave the way to a commercial product. The team also hopes to expand access in the meantime through larger clinical trials with patients in additional locations.
The work builds on accumulating research exploring vibration and other stimulation therapies as treatments for neurological conditions. Other vibrating gloves have helped reduce involuntary movement for patients with Parkinson’s. And the University of Kansas Medical Center, Kansas City, will soon trial the Food and Drug Administration–approved vagal nerve stimulator, an implantable device intended to treat motor function in stroke survivors. Dr. Okamura noted that devices use “different types of vibration patterns and intensities,” depending on the disease state they target.
Spasticity often develops or worsens months after a stroke. By then, patients may have run out of insurance coverage for rehabilitation. And the effectiveness of Botox injections can “wear out over time,” Dr. Okamura said.
In a clinical trial, patients wore the device for 3 hours a day for 8 weeks, while doing their usual activities. The researchers continued testing their spasticity for 2 more weeks.
How Vibro-Tactile Stimulation May Rewire the Brain
The device originated at Georgia Tech, where Dr. Okamura’s postdoctoral research fellow Caitlyn Seim, PhD, was using vibro-tactile stimulation (VTS) to teach people skills, such as playing the piano, using touch-feedback training. The team decided to target spasticity, which VTS had helped in previousstudies of in-clinic (non-wearable) devices.
How does the device work? The researchers point to neuroplasticity, the ability of neurons to create new synapses or strengthen existing ones in the brain.
“The stimulation is sending additional sensory signals to the brain, which helps the brain interpret and reconnect any lost circuits,” Dr. Okamura said.
Spasticity is driven by “an imbalance in the excitatory drive to the muscles,” she continued. This can lead to worsening contractions, until a hand closes into a fist or a foot curls up. (The team has also done preliminary research on a similar device for foot spasticity, which they hope to continue developing.) Previous studies by Okamura and others suggest that vibration stimulation may prevent these contractions, both in the short and long term.
“Immediately, we do see some softening of the muscles,” Dr. Okamura said. “But in our longer-term study, where we compared to Botox, I also think that the vibration may be retraining the brain to send inhibitory signals. And that can restore balance that’s lost due to the damaged neural circuits from a stroke.”
When the team did a separate study comparing the effects of muscle and skin stimulation, they hypothesized that the vibration could be having a biomechanical effect on the muscle. Instead, they found that stimulating the skin had a greater impact — a “somewhat unexpected” result, Dr. Okamura said. That led them to the brain.
“Stimulating the skin is really about creating sensory signals that get sent to the brain,” Dr. Okamura said, “which is why we think it’s actually a brain-retraining effect and not a direct biomechanical effect.”
What’s Next?
The researchers are seeking funding for longer-term clinical studies to find out if effects persist beyond 2 weeks. They also want to explore how long and often patients should wear the glove for best results.
The researchers also want to study how movement might enhance the effects of the device.
“One of the treatments for spasticity — medications aside, this vibration machine aside — is more exercise, more passive range of motion,” said Oluwole O. Awosika, MD, associate professor at the University of Cincinnati College of Medicine, who was not involved in the study. “It would have been nice to have a control group that didn’t get any of this stimulation or that was only encouraged to do 3 hours of movement a day. What would the difference be?”
Dr. Awosika also wondered how easy it would be for stroke patients without in-home assistance to use the device. “Sometimes wearing these devices requires someone to put it on,” he said.
Of course, if all goes well, patients wouldn’t have to deal with that forever. “The dream would be that you reach true rehabilitation, which is no longer needing the device,” Dr. Okamura said.
A version of this article appeared on Medscape.com.
How the New MRSA Antibiotic Cracked AI’s ‘Black Box’
“New antibiotics discovered using AI!”
That’s how headlines read in December 2023, when MIT researchers announced a new class of antibiotics that could wipe out the drug-resistant superbug methicillin-resistant Staphylococcus aureus (MRSA) in mice.
Powered by deep learning, the study was a significant breakthrough. Few new antibiotics have come out since the 1960s, and this one in particular could be crucial in fighting tough-to-treat MRSA, which kills more than 10,000 people annually in the United States.
But as remarkable as the antibiotic discovery was, it may not be the most impactful part of this study.
“Of course, we view the antibiotic-discovery angle to be very important,” said Felix Wong, PhD, a colead author of the study and postdoctoral fellow at the Broad Institute of MIT and Harvard, Cambridge, Massachusetts. “But I think equally important, or maybe even more important, is really our method of opening up the black box.”
The black box is generally thought of as impenetrable in complex machine learning models, and that poses a challenge in the drug discovery realm.
“A major bottleneck in AI-ML-driven drug discovery is that nobody knows what the heck is going on,” said Dr. Wong. Models have such powerful architectures that their decision-making is mysterious.
Researchers input data, such as patient features, and the model says what drugs might be effective. But researchers have no idea how the model arrived at its predictions — until now.
What the Researchers Did
Dr. Wong and his colleagues first mined 39,000 compounds for antibiotic activity against MRSA. They fed information about the compounds’ chemical structures and antibiotic activity into their machine learning model. With this, they “trained” the model to predict whether a compound is antibacterial.
Next, they used additional deep learning to narrow the field, ruling out compounds toxic to humans. Then, deploying their various models at once, they screened 12 million commercially available compounds. Five classes emerged as likely MRSA fighters. Further testing of 280 compounds from the five classes produced the final results: Two compounds from the same class. Both reduced MRSA infection in mouse models.
How did the computer flag these compounds? The researchers sought to answer that question by figuring out which chemical structures the model had been looking for.
A chemical structure can be “pruned” — that is, scientists can remove certain atoms and bonds to reveal an underlying substructure. The MIT researchers used the Monte Carlo Tree Search, a commonly used algorithm in machine learning, to select which atoms and bonds to edit out. Then they fed the pruned substructures into their model to find out which was likely responsible for the antibacterial activity.
“The main idea is we can pinpoint which substructure of a chemical structure is causative instead of just correlated with high antibiotic activity,” Dr. Wong said.
This could fuel new “design-driven” or generative AI approaches where these substructures become “starting points to design entirely unseen, unprecedented antibiotics,” Dr. Wong said. “That’s one of the key efforts that we’ve been working on since the publication of this paper.”
More broadly, their method could lead to discoveries in drug classes beyond antibiotics, such as antivirals and anticancer drugs, according to Dr. Wong.
“This is the first major study that I’ve seen seeking to incorporate explainability into deep learning models in the context of antibiotics,” said César de la Fuente, PhD, an assistant professor at the University of Pennsylvania, Philadelphia, Pennsylvania, whose lab has been engaged in AI for antibiotic discovery for the past 5 years.
“It’s kind of like going into the black box with a magnifying lens and figuring out what is actually happening in there,” Dr. de la Fuente said. “And that will open up possibilities for leveraging those different steps to make better drugs.”
How Explainable AI Could Revolutionize Medicine
In studies, explainable AI is showing its potential for informing clinical decisions as well — flagging high-risk patients and letting doctors know why that calculation was made. University of Washington researchers have used the technology to predict whether a patient will have hypoxemia during surgery, revealing which features contributed to the prediction, such as blood pressure or body mass index. Another study used explainable AI to help emergency medical services providers and emergency room clinicians optimize time — for example, by identifying trauma patients at high risk for acute traumatic coagulopathy more quickly.
A crucial benefit of explainable AI is its ability to audit machine learning models for mistakes, said Su-In Lee, PhD, a computer scientist who led the UW research.
For example, a surge of research during the pandemic suggested that AI models could predict COVID-19 infection based on chest x-rays. Dr. Lee’s research used explainable AI to show that many of the studies were not as accurate as they claimed. Her lab revealed that many models› decisions were based not on pathologies but rather on other aspects such as laterality markers in the corners of x-rays or medical devices worn by patients (like pacemakers). She applied the same model auditing technique to AI-powered dermatology devices, digging into the flawed reasoning in their melanoma predictions.
Explainable AI is beginning to affect drug development too. A 2023 study led by Dr. Lee used it to explain how to select complementary drugs for acute myeloid leukemia patients based on the differentiation levels of cancer cells. And in two other studies aimed at identifying Alzheimer’s therapeutic targets, “explainable AI played a key role in terms of identifying the driver pathway,” she said.
Currently, the US Food and Drug Administration (FDA) approval doesn’t require an understanding of a drug’s mechanism of action. But the issue is being raised more often, including at December’s Health Regulatory Policy Conference at MIT’s Jameel Clinic. And just over a year ago, Dr. Lee predicted that the FDA approval process would come to incorporate explainable AI analysis.
“I didn’t hesitate,” Dr. Lee said, regarding her prediction. “We didn’t see this in 2023, so I won’t assert that I was right, but I can confidently say that we are progressing in that direction.”
What’s Next?
The MIT study is part of the Antibiotics-AI project, a 7-year effort to leverage AI to find new antibiotics. Phare Bio, a nonprofit started by MIT professor James Collins, PhD, and others, will do clinical testing on the antibiotic candidates.
Even with the AI’s assistance, there’s still a long way to go before clinical approval.
But knowing which elements contribute to a candidate’s effectiveness against MRSA could help the researchers formulate scientific hypotheses and design better validation, Dr. Lee noted. In other words, because they used explainable AI, they could be better positioned for clinical trial success.
A version of this article appeared on Medscape.com.
“New antibiotics discovered using AI!”
That’s how headlines read in December 2023, when MIT researchers announced a new class of antibiotics that could wipe out the drug-resistant superbug methicillin-resistant Staphylococcus aureus (MRSA) in mice.
Powered by deep learning, the study was a significant breakthrough. Few new antibiotics have come out since the 1960s, and this one in particular could be crucial in fighting tough-to-treat MRSA, which kills more than 10,000 people annually in the United States.
But as remarkable as the antibiotic discovery was, it may not be the most impactful part of this study.
“Of course, we view the antibiotic-discovery angle to be very important,” said Felix Wong, PhD, a colead author of the study and postdoctoral fellow at the Broad Institute of MIT and Harvard, Cambridge, Massachusetts. “But I think equally important, or maybe even more important, is really our method of opening up the black box.”
The black box is generally thought of as impenetrable in complex machine learning models, and that poses a challenge in the drug discovery realm.
“A major bottleneck in AI-ML-driven drug discovery is that nobody knows what the heck is going on,” said Dr. Wong. Models have such powerful architectures that their decision-making is mysterious.
Researchers input data, such as patient features, and the model says what drugs might be effective. But researchers have no idea how the model arrived at its predictions — until now.
What the Researchers Did
Dr. Wong and his colleagues first mined 39,000 compounds for antibiotic activity against MRSA. They fed information about the compounds’ chemical structures and antibiotic activity into their machine learning model. With this, they “trained” the model to predict whether a compound is antibacterial.
Next, they used additional deep learning to narrow the field, ruling out compounds toxic to humans. Then, deploying their various models at once, they screened 12 million commercially available compounds. Five classes emerged as likely MRSA fighters. Further testing of 280 compounds from the five classes produced the final results: Two compounds from the same class. Both reduced MRSA infection in mouse models.
How did the computer flag these compounds? The researchers sought to answer that question by figuring out which chemical structures the model had been looking for.
A chemical structure can be “pruned” — that is, scientists can remove certain atoms and bonds to reveal an underlying substructure. The MIT researchers used the Monte Carlo Tree Search, a commonly used algorithm in machine learning, to select which atoms and bonds to edit out. Then they fed the pruned substructures into their model to find out which was likely responsible for the antibacterial activity.
“The main idea is we can pinpoint which substructure of a chemical structure is causative instead of just correlated with high antibiotic activity,” Dr. Wong said.
This could fuel new “design-driven” or generative AI approaches where these substructures become “starting points to design entirely unseen, unprecedented antibiotics,” Dr. Wong said. “That’s one of the key efforts that we’ve been working on since the publication of this paper.”
More broadly, their method could lead to discoveries in drug classes beyond antibiotics, such as antivirals and anticancer drugs, according to Dr. Wong.
“This is the first major study that I’ve seen seeking to incorporate explainability into deep learning models in the context of antibiotics,” said César de la Fuente, PhD, an assistant professor at the University of Pennsylvania, Philadelphia, Pennsylvania, whose lab has been engaged in AI for antibiotic discovery for the past 5 years.
“It’s kind of like going into the black box with a magnifying lens and figuring out what is actually happening in there,” Dr. de la Fuente said. “And that will open up possibilities for leveraging those different steps to make better drugs.”
How Explainable AI Could Revolutionize Medicine
In studies, explainable AI is showing its potential for informing clinical decisions as well — flagging high-risk patients and letting doctors know why that calculation was made. University of Washington researchers have used the technology to predict whether a patient will have hypoxemia during surgery, revealing which features contributed to the prediction, such as blood pressure or body mass index. Another study used explainable AI to help emergency medical services providers and emergency room clinicians optimize time — for example, by identifying trauma patients at high risk for acute traumatic coagulopathy more quickly.
A crucial benefit of explainable AI is its ability to audit machine learning models for mistakes, said Su-In Lee, PhD, a computer scientist who led the UW research.
For example, a surge of research during the pandemic suggested that AI models could predict COVID-19 infection based on chest x-rays. Dr. Lee’s research used explainable AI to show that many of the studies were not as accurate as they claimed. Her lab revealed that many models› decisions were based not on pathologies but rather on other aspects such as laterality markers in the corners of x-rays or medical devices worn by patients (like pacemakers). She applied the same model auditing technique to AI-powered dermatology devices, digging into the flawed reasoning in their melanoma predictions.
Explainable AI is beginning to affect drug development too. A 2023 study led by Dr. Lee used it to explain how to select complementary drugs for acute myeloid leukemia patients based on the differentiation levels of cancer cells. And in two other studies aimed at identifying Alzheimer’s therapeutic targets, “explainable AI played a key role in terms of identifying the driver pathway,” she said.
Currently, the US Food and Drug Administration (FDA) approval doesn’t require an understanding of a drug’s mechanism of action. But the issue is being raised more often, including at December’s Health Regulatory Policy Conference at MIT’s Jameel Clinic. And just over a year ago, Dr. Lee predicted that the FDA approval process would come to incorporate explainable AI analysis.
“I didn’t hesitate,” Dr. Lee said, regarding her prediction. “We didn’t see this in 2023, so I won’t assert that I was right, but I can confidently say that we are progressing in that direction.”
What’s Next?
The MIT study is part of the Antibiotics-AI project, a 7-year effort to leverage AI to find new antibiotics. Phare Bio, a nonprofit started by MIT professor James Collins, PhD, and others, will do clinical testing on the antibiotic candidates.
Even with the AI’s assistance, there’s still a long way to go before clinical approval.
But knowing which elements contribute to a candidate’s effectiveness against MRSA could help the researchers formulate scientific hypotheses and design better validation, Dr. Lee noted. In other words, because they used explainable AI, they could be better positioned for clinical trial success.
A version of this article appeared on Medscape.com.
“New antibiotics discovered using AI!”
That’s how headlines read in December 2023, when MIT researchers announced a new class of antibiotics that could wipe out the drug-resistant superbug methicillin-resistant Staphylococcus aureus (MRSA) in mice.
Powered by deep learning, the study was a significant breakthrough. Few new antibiotics have come out since the 1960s, and this one in particular could be crucial in fighting tough-to-treat MRSA, which kills more than 10,000 people annually in the United States.
But as remarkable as the antibiotic discovery was, it may not be the most impactful part of this study.
“Of course, we view the antibiotic-discovery angle to be very important,” said Felix Wong, PhD, a colead author of the study and postdoctoral fellow at the Broad Institute of MIT and Harvard, Cambridge, Massachusetts. “But I think equally important, or maybe even more important, is really our method of opening up the black box.”
The black box is generally thought of as impenetrable in complex machine learning models, and that poses a challenge in the drug discovery realm.
“A major bottleneck in AI-ML-driven drug discovery is that nobody knows what the heck is going on,” said Dr. Wong. Models have such powerful architectures that their decision-making is mysterious.
Researchers input data, such as patient features, and the model says what drugs might be effective. But researchers have no idea how the model arrived at its predictions — until now.
What the Researchers Did
Dr. Wong and his colleagues first mined 39,000 compounds for antibiotic activity against MRSA. They fed information about the compounds’ chemical structures and antibiotic activity into their machine learning model. With this, they “trained” the model to predict whether a compound is antibacterial.
Next, they used additional deep learning to narrow the field, ruling out compounds toxic to humans. Then, deploying their various models at once, they screened 12 million commercially available compounds. Five classes emerged as likely MRSA fighters. Further testing of 280 compounds from the five classes produced the final results: Two compounds from the same class. Both reduced MRSA infection in mouse models.
How did the computer flag these compounds? The researchers sought to answer that question by figuring out which chemical structures the model had been looking for.
A chemical structure can be “pruned” — that is, scientists can remove certain atoms and bonds to reveal an underlying substructure. The MIT researchers used the Monte Carlo Tree Search, a commonly used algorithm in machine learning, to select which atoms and bonds to edit out. Then they fed the pruned substructures into their model to find out which was likely responsible for the antibacterial activity.
“The main idea is we can pinpoint which substructure of a chemical structure is causative instead of just correlated with high antibiotic activity,” Dr. Wong said.
This could fuel new “design-driven” or generative AI approaches where these substructures become “starting points to design entirely unseen, unprecedented antibiotics,” Dr. Wong said. “That’s one of the key efforts that we’ve been working on since the publication of this paper.”
More broadly, their method could lead to discoveries in drug classes beyond antibiotics, such as antivirals and anticancer drugs, according to Dr. Wong.
“This is the first major study that I’ve seen seeking to incorporate explainability into deep learning models in the context of antibiotics,” said César de la Fuente, PhD, an assistant professor at the University of Pennsylvania, Philadelphia, Pennsylvania, whose lab has been engaged in AI for antibiotic discovery for the past 5 years.
“It’s kind of like going into the black box with a magnifying lens and figuring out what is actually happening in there,” Dr. de la Fuente said. “And that will open up possibilities for leveraging those different steps to make better drugs.”
How Explainable AI Could Revolutionize Medicine
In studies, explainable AI is showing its potential for informing clinical decisions as well — flagging high-risk patients and letting doctors know why that calculation was made. University of Washington researchers have used the technology to predict whether a patient will have hypoxemia during surgery, revealing which features contributed to the prediction, such as blood pressure or body mass index. Another study used explainable AI to help emergency medical services providers and emergency room clinicians optimize time — for example, by identifying trauma patients at high risk for acute traumatic coagulopathy more quickly.
A crucial benefit of explainable AI is its ability to audit machine learning models for mistakes, said Su-In Lee, PhD, a computer scientist who led the UW research.
For example, a surge of research during the pandemic suggested that AI models could predict COVID-19 infection based on chest x-rays. Dr. Lee’s research used explainable AI to show that many of the studies were not as accurate as they claimed. Her lab revealed that many models› decisions were based not on pathologies but rather on other aspects such as laterality markers in the corners of x-rays or medical devices worn by patients (like pacemakers). She applied the same model auditing technique to AI-powered dermatology devices, digging into the flawed reasoning in their melanoma predictions.
Explainable AI is beginning to affect drug development too. A 2023 study led by Dr. Lee used it to explain how to select complementary drugs for acute myeloid leukemia patients based on the differentiation levels of cancer cells. And in two other studies aimed at identifying Alzheimer’s therapeutic targets, “explainable AI played a key role in terms of identifying the driver pathway,” she said.
Currently, the US Food and Drug Administration (FDA) approval doesn’t require an understanding of a drug’s mechanism of action. But the issue is being raised more often, including at December’s Health Regulatory Policy Conference at MIT’s Jameel Clinic. And just over a year ago, Dr. Lee predicted that the FDA approval process would come to incorporate explainable AI analysis.
“I didn’t hesitate,” Dr. Lee said, regarding her prediction. “We didn’t see this in 2023, so I won’t assert that I was right, but I can confidently say that we are progressing in that direction.”
What’s Next?
The MIT study is part of the Antibiotics-AI project, a 7-year effort to leverage AI to find new antibiotics. Phare Bio, a nonprofit started by MIT professor James Collins, PhD, and others, will do clinical testing on the antibiotic candidates.
Even with the AI’s assistance, there’s still a long way to go before clinical approval.
But knowing which elements contribute to a candidate’s effectiveness against MRSA could help the researchers formulate scientific hypotheses and design better validation, Dr. Lee noted. In other words, because they used explainable AI, they could be better positioned for clinical trial success.
A version of this article appeared on Medscape.com.
AI app can do biomechanical analysis in minutes
Stanford (Calif.) University’s human performance lab sits next to its physical therapy clinic, so orthopedic surgeons often stop by to request biomechanical analyses for their patients, such as athletes with repeat injuries.
“It would take us days to analyze the data, so we would only do it a handful of times per year,” said Scott Uhlrich, PhD, director of research at the lab.
Now an app can do the job in less than 10 minutes.
The motion-capture app, created by Dr. Uhlrich and fellow bioengineers at Stanford, could help clinicians design better interventions to ward off mobility problems and speed recovery. It could also help researchers fill huge knowledge gaps about human mobility.
It’s currently available free for research and educational use. Model Health, a startup affiliated with the Stanford researchers, provides licenses for commercial use and clinical practice.
Here’s how it works. Footage of human movement, recorded by two smartphones, gets uploaded to the cloud, where an algorithm identifies a set of points on the body. The app relies on computer vision algorithms, a form of AI that trains computers to “understand” visual data – in this case, a person’s pose.
Next, the app quantifies how the body is moving through three-dimensional space. Musculoskeletal system models reveal insights into that movement, such as the angle of a joint, the stretch in a tendon, or the force being transferred through the joints.
“These are the quantities that relate to injuries and disease,” said Dr. Uhlrich, co-author of a study introducing the app. “We need to get to those quantities to be able to inform medical research and eventually clinical practice.”
The conventional approach to getting this kind of analysis requires special expertise and costs $150,000. By contrast, the app is free and easy to use.
It “democratizes” human movement analysis, said senior study author Scott Delp, PhD, professor of bioengineering and mechanical engineering at Stanford. The researchers hope this will “improve outcomes for patients across the world.”
‘Endless opportunities’
A lot about human mobility remains mysterious.
In aging adults, researchers can’t say when balance starts to degrade or by how much every year. They’re also still unraveling how sports injuries occur and how degenerative joint diseases like arthritis progress.
“We don’t really understand the onset of a lot of things, because we’ve just never measured it,” Dr. Uhlrich said.
OpenCap could help change that in a big way. Although biomechanics studies tend to be small – just 14 participants, on average – the app could allow for much larger studies, thanks to its lower cost and ease of use. In the study, the app collected movement data on 100 participants in less than 10 hours and computed results in 31 hours – an effort that would otherwise have taken a year.
“Studies of hundreds will be common, and thousands will be feasible, especially if assessments are integrated into clinic visits,” Dr. Uhlrich said.
About 2,600 researchers around the world are already using the app, according to Dr. Uhlrich. Many had never created a dynamic simulation before.
“The opportunities here are endless,” said Eni Halilaj, PhD, an assistant professor of mechanical engineering at Carnegie Mellon, Pittsburgh, who was not involved in creating the app. That’s especially true for “highly heterogeneous conditions that we have not been able to fully characterize through traditional studies with limited patients.”
In one case, researcher Reed Gurchiek, a former Stanford postdoc and current professor at Clemson (S.C.) University, used the app to study hamstring strain injuries during sprinting and found that these muscles lengthen faster during acceleration, compared with running at a constant speed.
“This aligns with the higher observed injury rates when athletes are accelerating,” Dr. Uhlrich explained. “Varied-speed sprinting studies are not possible in the lab, so this was really enabled by OpenCap’s portability.”
Movement as a biomarker
The researchers are already using the app to build new tools, including metrics to identify risk for anterior cruciate ligament injury in young athletes and to measure balance.
Someday, the technology could augment annual physicals, establishing movement as a biomarker. By having patients perform a few movements, like walking or standing up, clinicians could assess their disease risk and progression or their risk of falling.
Excessive loading in the knee joint puts patients at higher risk of developing osteoarthritis, for instance, but clinicians can’t easily access this information. The disease is typically diagnosed after symptoms appear, even though intervention could happen much earlier.
“Prevention is still not as embraced as it should be,” said Pamela Toto, PhD, professor of occupational therapy at the University of Pittsburgh, who also was not involved in making the app. “If we could tie the technology to intervention down the road, that could be valuable.”
A version of this article first appeared on Medscape.com.
Stanford (Calif.) University’s human performance lab sits next to its physical therapy clinic, so orthopedic surgeons often stop by to request biomechanical analyses for their patients, such as athletes with repeat injuries.
“It would take us days to analyze the data, so we would only do it a handful of times per year,” said Scott Uhlrich, PhD, director of research at the lab.
Now an app can do the job in less than 10 minutes.
The motion-capture app, created by Dr. Uhlrich and fellow bioengineers at Stanford, could help clinicians design better interventions to ward off mobility problems and speed recovery. It could also help researchers fill huge knowledge gaps about human mobility.
It’s currently available free for research and educational use. Model Health, a startup affiliated with the Stanford researchers, provides licenses for commercial use and clinical practice.
Here’s how it works. Footage of human movement, recorded by two smartphones, gets uploaded to the cloud, where an algorithm identifies a set of points on the body. The app relies on computer vision algorithms, a form of AI that trains computers to “understand” visual data – in this case, a person’s pose.
Next, the app quantifies how the body is moving through three-dimensional space. Musculoskeletal system models reveal insights into that movement, such as the angle of a joint, the stretch in a tendon, or the force being transferred through the joints.
“These are the quantities that relate to injuries and disease,” said Dr. Uhlrich, co-author of a study introducing the app. “We need to get to those quantities to be able to inform medical research and eventually clinical practice.”
The conventional approach to getting this kind of analysis requires special expertise and costs $150,000. By contrast, the app is free and easy to use.
It “democratizes” human movement analysis, said senior study author Scott Delp, PhD, professor of bioengineering and mechanical engineering at Stanford. The researchers hope this will “improve outcomes for patients across the world.”
‘Endless opportunities’
A lot about human mobility remains mysterious.
In aging adults, researchers can’t say when balance starts to degrade or by how much every year. They’re also still unraveling how sports injuries occur and how degenerative joint diseases like arthritis progress.
“We don’t really understand the onset of a lot of things, because we’ve just never measured it,” Dr. Uhlrich said.
OpenCap could help change that in a big way. Although biomechanics studies tend to be small – just 14 participants, on average – the app could allow for much larger studies, thanks to its lower cost and ease of use. In the study, the app collected movement data on 100 participants in less than 10 hours and computed results in 31 hours – an effort that would otherwise have taken a year.
“Studies of hundreds will be common, and thousands will be feasible, especially if assessments are integrated into clinic visits,” Dr. Uhlrich said.
About 2,600 researchers around the world are already using the app, according to Dr. Uhlrich. Many had never created a dynamic simulation before.
“The opportunities here are endless,” said Eni Halilaj, PhD, an assistant professor of mechanical engineering at Carnegie Mellon, Pittsburgh, who was not involved in creating the app. That’s especially true for “highly heterogeneous conditions that we have not been able to fully characterize through traditional studies with limited patients.”
In one case, researcher Reed Gurchiek, a former Stanford postdoc and current professor at Clemson (S.C.) University, used the app to study hamstring strain injuries during sprinting and found that these muscles lengthen faster during acceleration, compared with running at a constant speed.
“This aligns with the higher observed injury rates when athletes are accelerating,” Dr. Uhlrich explained. “Varied-speed sprinting studies are not possible in the lab, so this was really enabled by OpenCap’s portability.”
Movement as a biomarker
The researchers are already using the app to build new tools, including metrics to identify risk for anterior cruciate ligament injury in young athletes and to measure balance.
Someday, the technology could augment annual physicals, establishing movement as a biomarker. By having patients perform a few movements, like walking or standing up, clinicians could assess their disease risk and progression or their risk of falling.
Excessive loading in the knee joint puts patients at higher risk of developing osteoarthritis, for instance, but clinicians can’t easily access this information. The disease is typically diagnosed after symptoms appear, even though intervention could happen much earlier.
“Prevention is still not as embraced as it should be,” said Pamela Toto, PhD, professor of occupational therapy at the University of Pittsburgh, who also was not involved in making the app. “If we could tie the technology to intervention down the road, that could be valuable.”
A version of this article first appeared on Medscape.com.
Stanford (Calif.) University’s human performance lab sits next to its physical therapy clinic, so orthopedic surgeons often stop by to request biomechanical analyses for their patients, such as athletes with repeat injuries.
“It would take us days to analyze the data, so we would only do it a handful of times per year,” said Scott Uhlrich, PhD, director of research at the lab.
Now an app can do the job in less than 10 minutes.
The motion-capture app, created by Dr. Uhlrich and fellow bioengineers at Stanford, could help clinicians design better interventions to ward off mobility problems and speed recovery. It could also help researchers fill huge knowledge gaps about human mobility.
It’s currently available free for research and educational use. Model Health, a startup affiliated with the Stanford researchers, provides licenses for commercial use and clinical practice.
Here’s how it works. Footage of human movement, recorded by two smartphones, gets uploaded to the cloud, where an algorithm identifies a set of points on the body. The app relies on computer vision algorithms, a form of AI that trains computers to “understand” visual data – in this case, a person’s pose.
Next, the app quantifies how the body is moving through three-dimensional space. Musculoskeletal system models reveal insights into that movement, such as the angle of a joint, the stretch in a tendon, or the force being transferred through the joints.
“These are the quantities that relate to injuries and disease,” said Dr. Uhlrich, co-author of a study introducing the app. “We need to get to those quantities to be able to inform medical research and eventually clinical practice.”
The conventional approach to getting this kind of analysis requires special expertise and costs $150,000. By contrast, the app is free and easy to use.
It “democratizes” human movement analysis, said senior study author Scott Delp, PhD, professor of bioengineering and mechanical engineering at Stanford. The researchers hope this will “improve outcomes for patients across the world.”
‘Endless opportunities’
A lot about human mobility remains mysterious.
In aging adults, researchers can’t say when balance starts to degrade or by how much every year. They’re also still unraveling how sports injuries occur and how degenerative joint diseases like arthritis progress.
“We don’t really understand the onset of a lot of things, because we’ve just never measured it,” Dr. Uhlrich said.
OpenCap could help change that in a big way. Although biomechanics studies tend to be small – just 14 participants, on average – the app could allow for much larger studies, thanks to its lower cost and ease of use. In the study, the app collected movement data on 100 participants in less than 10 hours and computed results in 31 hours – an effort that would otherwise have taken a year.
“Studies of hundreds will be common, and thousands will be feasible, especially if assessments are integrated into clinic visits,” Dr. Uhlrich said.
About 2,600 researchers around the world are already using the app, according to Dr. Uhlrich. Many had never created a dynamic simulation before.
“The opportunities here are endless,” said Eni Halilaj, PhD, an assistant professor of mechanical engineering at Carnegie Mellon, Pittsburgh, who was not involved in creating the app. That’s especially true for “highly heterogeneous conditions that we have not been able to fully characterize through traditional studies with limited patients.”
In one case, researcher Reed Gurchiek, a former Stanford postdoc and current professor at Clemson (S.C.) University, used the app to study hamstring strain injuries during sprinting and found that these muscles lengthen faster during acceleration, compared with running at a constant speed.
“This aligns with the higher observed injury rates when athletes are accelerating,” Dr. Uhlrich explained. “Varied-speed sprinting studies are not possible in the lab, so this was really enabled by OpenCap’s portability.”
Movement as a biomarker
The researchers are already using the app to build new tools, including metrics to identify risk for anterior cruciate ligament injury in young athletes and to measure balance.
Someday, the technology could augment annual physicals, establishing movement as a biomarker. By having patients perform a few movements, like walking or standing up, clinicians could assess their disease risk and progression or their risk of falling.
Excessive loading in the knee joint puts patients at higher risk of developing osteoarthritis, for instance, but clinicians can’t easily access this information. The disease is typically diagnosed after symptoms appear, even though intervention could happen much earlier.
“Prevention is still not as embraced as it should be,” said Pamela Toto, PhD, professor of occupational therapy at the University of Pittsburgh, who also was not involved in making the app. “If we could tie the technology to intervention down the road, that could be valuable.”
A version of this article first appeared on Medscape.com.
3D-printed meds customize the exact dose for sick children
Convincing kids to take their medicine could become much easier. Researchers at Texas A&M University are developing a new method of pharmaceutical 3D printing with pediatric patients in mind.
They hope to print precisely dosed tablets in child-friendly shapes and flavors. While the effort is focused on two drugs for pediatric AIDS, the process could be used to print other medicines, including for adults.
Researchers from Britain, Australia, and the University of Texas at Austin are also in the early stages of 3D-printed medication projects. It’s a promising venture in the broader pursuit of “personalized medicine,” tailoring treatments to each patient’s unique needs.
Drug mass production fails to address pediatric patients, who often need different dosages and combinations of medicines as they grow. As a result, adult tablets are often crushed and dissolved in liquid – known as compounding – and given to children. But this can harm drug quality and make doses less precise.
“Suppose the child needs 3.4 milligrams and only a 10-milligram tablet is available. Once you manipulate the dosage from solid to liquid, how do you ensure that it has the same amount of drug in it?” said co-principal investigator Mansoor Khan, PhD, a professor of pharmaceutical sciences at Texas A&M.
Most pharmacies lack the equipment to test compounded drug quality, he said. And liquified drugs taste bad because the pill coating has been ground away.
“Flavor is a big issue,” said Olive Eckstein, MD, an assistant professor of pediatric hematology-oncology at Texas Children’s Hospital and Baylor College of Medicine, who is not involved in the research. “Hospitals will sometimes delay discharging pediatric patients because they can’t take their meds orally and have to get an IV formulation.”
Updating pharmaceutical 3D printing
The FDA approved a 3D-printed drug in 2015, but since then, progress has stalled, largely because the method relied on solvents to bind drug particles together. Over time, solvents can compromise shelf life, according to co-principal investigator Mathew Kuttolamadom, PhD, an associate professor of engineering at Texas A&M.
The Texas A&M team is using a different method, without solvents. First, they create a powder mixture of the drug, a biocompatible polymer (such as lactose), and a sheen, a pigment that colors the tablet and allows heat to be absorbed. Flavoring can also be added. Next, the mixture is heated in the printer chamber.
“The polymer should melt just enough. That gives the tablet structural strength. But it should not melt too much, whereby the drug can start dissolving into the polymer,” Dr. Kuttolamadom said.
The tablets are finished with precise applications of laser heat. Using computer-aided design software, the researchers can create tablets in almost any shape, such as “stars or teddy bears,” he said.
After much trial and error, the researchers have printed tablets that won’t break apart or become soggy.
Now they are testing how different laser scan speeds affect the structure of the tablet, which in turn affects the rate at which drugs dissolve. Slowing down the laser imparts more energy, strengthening the tablet structure and making drugs dissolve slower, for a longer release inside the body.
The researchers hope to develop machine learning models to test different laser speed combinations. Eventually, they could create tablets that combine drugs with different dissolve rates.
“The outside could be a rapid release, and the inside could be an extended release or a sustained release, or even a completely different drug,” Dr. Kuttolamadom said.
Older patients who take many daily medications could benefit from the technology. “Personalized tablets could be printed at your local pharmacy,” he said, “even before you leave your doctor’s office.”
A version of this article first appeared on WebMD.com.
Convincing kids to take their medicine could become much easier. Researchers at Texas A&M University are developing a new method of pharmaceutical 3D printing with pediatric patients in mind.
They hope to print precisely dosed tablets in child-friendly shapes and flavors. While the effort is focused on two drugs for pediatric AIDS, the process could be used to print other medicines, including for adults.
Researchers from Britain, Australia, and the University of Texas at Austin are also in the early stages of 3D-printed medication projects. It’s a promising venture in the broader pursuit of “personalized medicine,” tailoring treatments to each patient’s unique needs.
Drug mass production fails to address pediatric patients, who often need different dosages and combinations of medicines as they grow. As a result, adult tablets are often crushed and dissolved in liquid – known as compounding – and given to children. But this can harm drug quality and make doses less precise.
“Suppose the child needs 3.4 milligrams and only a 10-milligram tablet is available. Once you manipulate the dosage from solid to liquid, how do you ensure that it has the same amount of drug in it?” said co-principal investigator Mansoor Khan, PhD, a professor of pharmaceutical sciences at Texas A&M.
Most pharmacies lack the equipment to test compounded drug quality, he said. And liquified drugs taste bad because the pill coating has been ground away.
“Flavor is a big issue,” said Olive Eckstein, MD, an assistant professor of pediatric hematology-oncology at Texas Children’s Hospital and Baylor College of Medicine, who is not involved in the research. “Hospitals will sometimes delay discharging pediatric patients because they can’t take their meds orally and have to get an IV formulation.”
Updating pharmaceutical 3D printing
The FDA approved a 3D-printed drug in 2015, but since then, progress has stalled, largely because the method relied on solvents to bind drug particles together. Over time, solvents can compromise shelf life, according to co-principal investigator Mathew Kuttolamadom, PhD, an associate professor of engineering at Texas A&M.
The Texas A&M team is using a different method, without solvents. First, they create a powder mixture of the drug, a biocompatible polymer (such as lactose), and a sheen, a pigment that colors the tablet and allows heat to be absorbed. Flavoring can also be added. Next, the mixture is heated in the printer chamber.
“The polymer should melt just enough. That gives the tablet structural strength. But it should not melt too much, whereby the drug can start dissolving into the polymer,” Dr. Kuttolamadom said.
The tablets are finished with precise applications of laser heat. Using computer-aided design software, the researchers can create tablets in almost any shape, such as “stars or teddy bears,” he said.
After much trial and error, the researchers have printed tablets that won’t break apart or become soggy.
Now they are testing how different laser scan speeds affect the structure of the tablet, which in turn affects the rate at which drugs dissolve. Slowing down the laser imparts more energy, strengthening the tablet structure and making drugs dissolve slower, for a longer release inside the body.
The researchers hope to develop machine learning models to test different laser speed combinations. Eventually, they could create tablets that combine drugs with different dissolve rates.
“The outside could be a rapid release, and the inside could be an extended release or a sustained release, or even a completely different drug,” Dr. Kuttolamadom said.
Older patients who take many daily medications could benefit from the technology. “Personalized tablets could be printed at your local pharmacy,” he said, “even before you leave your doctor’s office.”
A version of this article first appeared on WebMD.com.
Convincing kids to take their medicine could become much easier. Researchers at Texas A&M University are developing a new method of pharmaceutical 3D printing with pediatric patients in mind.
They hope to print precisely dosed tablets in child-friendly shapes and flavors. While the effort is focused on two drugs for pediatric AIDS, the process could be used to print other medicines, including for adults.
Researchers from Britain, Australia, and the University of Texas at Austin are also in the early stages of 3D-printed medication projects. It’s a promising venture in the broader pursuit of “personalized medicine,” tailoring treatments to each patient’s unique needs.
Drug mass production fails to address pediatric patients, who often need different dosages and combinations of medicines as they grow. As a result, adult tablets are often crushed and dissolved in liquid – known as compounding – and given to children. But this can harm drug quality and make doses less precise.
“Suppose the child needs 3.4 milligrams and only a 10-milligram tablet is available. Once you manipulate the dosage from solid to liquid, how do you ensure that it has the same amount of drug in it?” said co-principal investigator Mansoor Khan, PhD, a professor of pharmaceutical sciences at Texas A&M.
Most pharmacies lack the equipment to test compounded drug quality, he said. And liquified drugs taste bad because the pill coating has been ground away.
“Flavor is a big issue,” said Olive Eckstein, MD, an assistant professor of pediatric hematology-oncology at Texas Children’s Hospital and Baylor College of Medicine, who is not involved in the research. “Hospitals will sometimes delay discharging pediatric patients because they can’t take their meds orally and have to get an IV formulation.”
Updating pharmaceutical 3D printing
The FDA approved a 3D-printed drug in 2015, but since then, progress has stalled, largely because the method relied on solvents to bind drug particles together. Over time, solvents can compromise shelf life, according to co-principal investigator Mathew Kuttolamadom, PhD, an associate professor of engineering at Texas A&M.
The Texas A&M team is using a different method, without solvents. First, they create a powder mixture of the drug, a biocompatible polymer (such as lactose), and a sheen, a pigment that colors the tablet and allows heat to be absorbed. Flavoring can also be added. Next, the mixture is heated in the printer chamber.
“The polymer should melt just enough. That gives the tablet structural strength. But it should not melt too much, whereby the drug can start dissolving into the polymer,” Dr. Kuttolamadom said.
The tablets are finished with precise applications of laser heat. Using computer-aided design software, the researchers can create tablets in almost any shape, such as “stars or teddy bears,” he said.
After much trial and error, the researchers have printed tablets that won’t break apart or become soggy.
Now they are testing how different laser scan speeds affect the structure of the tablet, which in turn affects the rate at which drugs dissolve. Slowing down the laser imparts more energy, strengthening the tablet structure and making drugs dissolve slower, for a longer release inside the body.
The researchers hope to develop machine learning models to test different laser speed combinations. Eventually, they could create tablets that combine drugs with different dissolve rates.
“The outside could be a rapid release, and the inside could be an extended release or a sustained release, or even a completely different drug,” Dr. Kuttolamadom said.
Older patients who take many daily medications could benefit from the technology. “Personalized tablets could be printed at your local pharmacy,” he said, “even before you leave your doctor’s office.”
A version of this article first appeared on WebMD.com.
How soybean oil could lead to gut inflammation
A popular ingredient in the American diet has been linked to ulcerative colitis. The ingredient is soybean oil, which is very common in processed foods. In fact, U.S. per capita consumption of soybean oil increased more than 1,000-fold during the 20th century.
In a study from the University of California, Riverside, and UC Davis, published in Gut Microbes, mice fed a diet high in soybean oil were more at risk of developing colitis.
The likely culprit? Linoleic acid, an omega-6 fatty acid that composes up to 60% of soybean oil.
Small amounts of linoleic acid help maintain the body’s water balance. But Americans derive as much as 10% of their daily energy from linoleic acid, when they need only 1%-2%, the researchers say.
The findings build on earlier research linking a high-linoleic acid diet with inflammatory bowel disease, or IBD, in humans. (Previous research in mice has also linked high consumption of the oil with obesity and diabetes in the rodents.)
For the new study, the researchers wanted to drill down into how linoleic acid affects the gut.
How linoleic acid may promote inflammation
In mice, the soybean oil diet upset the ratio of omega-3 to omega-6 fatty acids in the gut. This led to a decrease in endocannabinoids, lipid-based molecules that help block inflammation.
Enzymes that metabolize fatty acids are “shared between two pathways,” said study coauthor Frances Sladek, PhD, professor of cell biology at UC Riverside. “If you swamp the system with linoleic acid, you’ll have less enzymes available to metabolize omega-3s into good endocannabinoids.”
The endocannabinoid system has been linked to “visceral pain” in the gut, said Punyanganie de Silva, MD, MPH, an assistant professor at Brigham & Women’s Hospital, Boston, who was not involved in the study. But the relationship between the endocannabinoid system and inflammation has yet to be fully explored.
“This is one of the first papers that has looked at the association between linoleic acid and the endocannabinoid system,” Dr. de Silva said.
Changes in the gut microbiome
The gut microbiome of the mice also showed increased amounts of adherent invasive E. coli, a type of bacteria that grows by using linoleic acid as a carbon source. A “very close relative” of this bacteria has been linked to IBD in humans, Dr. Sladek said.
Using a method known as metabolomics, the researchers studied 3,000 metabolites in the intestinal cells of both the mice and the bacteria. Endocannabinoids decreased in both.
“We were actually quite surprised. I didn’t realize that bacteria made endocannabinoids,” Dr. Sladek said.
Helpful bacteria, such as the probiotic lactobacillus species, died off. The mice also had increased levels of oxylipins, which are correlated with obesity in mice and colitis in humans.
A high–linoleic acid diet could mean a leaky gut
Linoleic acid binds to a protein known as HNF-4 alpha. Disrupting the expression of this protein can weaken the intestinal barrier, letting toxins flow into the body – more commonly known as leaky gut. Mice on the soybean oil diet had decreased levels of the protein and more porous intestinal barriers, raising the risk for inflammation and colitis. “The HNF-4 alpha protein is conserved from mouse to human, so whatever’s happening to it in the context of the mouse gut, there’s a very high chance that a similar effect could be seen in humans as well,” said study coauthor Poonamjot Deol, PhD, an assistant professional researcher at UC Riverside.
Still, Dr. de Silva urges “some caution when interpreting these results,” given that “this is still experimental and needs to be reproduced in clinical studies as humans have a far more varied microbiome and more variable environmental exposures than these very controlled mouse model studies.”
Dr. de Silva says cooking with olive oil can “help increase omega-3 to omega-6 ratios” and advises eating a varied diet that includes omega-3 fats, such as flaxseed and walnuts, and minimal amounts of processed foods and saturated fats.
Looking ahead, endocannabinoids are being explored as “a potential therapy for treating IBD symptoms,” said Dr. Deol. She hopes to delve further into how linoleic acid affects the endocannabinoid system.
A version of this article first appeared on WebMD.com.
A popular ingredient in the American diet has been linked to ulcerative colitis. The ingredient is soybean oil, which is very common in processed foods. In fact, U.S. per capita consumption of soybean oil increased more than 1,000-fold during the 20th century.
In a study from the University of California, Riverside, and UC Davis, published in Gut Microbes, mice fed a diet high in soybean oil were more at risk of developing colitis.
The likely culprit? Linoleic acid, an omega-6 fatty acid that composes up to 60% of soybean oil.
Small amounts of linoleic acid help maintain the body’s water balance. But Americans derive as much as 10% of their daily energy from linoleic acid, when they need only 1%-2%, the researchers say.
The findings build on earlier research linking a high-linoleic acid diet with inflammatory bowel disease, or IBD, in humans. (Previous research in mice has also linked high consumption of the oil with obesity and diabetes in the rodents.)
For the new study, the researchers wanted to drill down into how linoleic acid affects the gut.
How linoleic acid may promote inflammation
In mice, the soybean oil diet upset the ratio of omega-3 to omega-6 fatty acids in the gut. This led to a decrease in endocannabinoids, lipid-based molecules that help block inflammation.
Enzymes that metabolize fatty acids are “shared between two pathways,” said study coauthor Frances Sladek, PhD, professor of cell biology at UC Riverside. “If you swamp the system with linoleic acid, you’ll have less enzymes available to metabolize omega-3s into good endocannabinoids.”
The endocannabinoid system has been linked to “visceral pain” in the gut, said Punyanganie de Silva, MD, MPH, an assistant professor at Brigham & Women’s Hospital, Boston, who was not involved in the study. But the relationship between the endocannabinoid system and inflammation has yet to be fully explored.
“This is one of the first papers that has looked at the association between linoleic acid and the endocannabinoid system,” Dr. de Silva said.
Changes in the gut microbiome
The gut microbiome of the mice also showed increased amounts of adherent invasive E. coli, a type of bacteria that grows by using linoleic acid as a carbon source. A “very close relative” of this bacteria has been linked to IBD in humans, Dr. Sladek said.
Using a method known as metabolomics, the researchers studied 3,000 metabolites in the intestinal cells of both the mice and the bacteria. Endocannabinoids decreased in both.
“We were actually quite surprised. I didn’t realize that bacteria made endocannabinoids,” Dr. Sladek said.
Helpful bacteria, such as the probiotic lactobacillus species, died off. The mice also had increased levels of oxylipins, which are correlated with obesity in mice and colitis in humans.
A high–linoleic acid diet could mean a leaky gut
Linoleic acid binds to a protein known as HNF-4 alpha. Disrupting the expression of this protein can weaken the intestinal barrier, letting toxins flow into the body – more commonly known as leaky gut. Mice on the soybean oil diet had decreased levels of the protein and more porous intestinal barriers, raising the risk for inflammation and colitis. “The HNF-4 alpha protein is conserved from mouse to human, so whatever’s happening to it in the context of the mouse gut, there’s a very high chance that a similar effect could be seen in humans as well,” said study coauthor Poonamjot Deol, PhD, an assistant professional researcher at UC Riverside.
Still, Dr. de Silva urges “some caution when interpreting these results,” given that “this is still experimental and needs to be reproduced in clinical studies as humans have a far more varied microbiome and more variable environmental exposures than these very controlled mouse model studies.”
Dr. de Silva says cooking with olive oil can “help increase omega-3 to omega-6 ratios” and advises eating a varied diet that includes omega-3 fats, such as flaxseed and walnuts, and minimal amounts of processed foods and saturated fats.
Looking ahead, endocannabinoids are being explored as “a potential therapy for treating IBD symptoms,” said Dr. Deol. She hopes to delve further into how linoleic acid affects the endocannabinoid system.
A version of this article first appeared on WebMD.com.
A popular ingredient in the American diet has been linked to ulcerative colitis. The ingredient is soybean oil, which is very common in processed foods. In fact, U.S. per capita consumption of soybean oil increased more than 1,000-fold during the 20th century.
In a study from the University of California, Riverside, and UC Davis, published in Gut Microbes, mice fed a diet high in soybean oil were more at risk of developing colitis.
The likely culprit? Linoleic acid, an omega-6 fatty acid that composes up to 60% of soybean oil.
Small amounts of linoleic acid help maintain the body’s water balance. But Americans derive as much as 10% of their daily energy from linoleic acid, when they need only 1%-2%, the researchers say.
The findings build on earlier research linking a high-linoleic acid diet with inflammatory bowel disease, or IBD, in humans. (Previous research in mice has also linked high consumption of the oil with obesity and diabetes in the rodents.)
For the new study, the researchers wanted to drill down into how linoleic acid affects the gut.
How linoleic acid may promote inflammation
In mice, the soybean oil diet upset the ratio of omega-3 to omega-6 fatty acids in the gut. This led to a decrease in endocannabinoids, lipid-based molecules that help block inflammation.
Enzymes that metabolize fatty acids are “shared between two pathways,” said study coauthor Frances Sladek, PhD, professor of cell biology at UC Riverside. “If you swamp the system with linoleic acid, you’ll have less enzymes available to metabolize omega-3s into good endocannabinoids.”
The endocannabinoid system has been linked to “visceral pain” in the gut, said Punyanganie de Silva, MD, MPH, an assistant professor at Brigham & Women’s Hospital, Boston, who was not involved in the study. But the relationship between the endocannabinoid system and inflammation has yet to be fully explored.
“This is one of the first papers that has looked at the association between linoleic acid and the endocannabinoid system,” Dr. de Silva said.
Changes in the gut microbiome
The gut microbiome of the mice also showed increased amounts of adherent invasive E. coli, a type of bacteria that grows by using linoleic acid as a carbon source. A “very close relative” of this bacteria has been linked to IBD in humans, Dr. Sladek said.
Using a method known as metabolomics, the researchers studied 3,000 metabolites in the intestinal cells of both the mice and the bacteria. Endocannabinoids decreased in both.
“We were actually quite surprised. I didn’t realize that bacteria made endocannabinoids,” Dr. Sladek said.
Helpful bacteria, such as the probiotic lactobacillus species, died off. The mice also had increased levels of oxylipins, which are correlated with obesity in mice and colitis in humans.
A high–linoleic acid diet could mean a leaky gut
Linoleic acid binds to a protein known as HNF-4 alpha. Disrupting the expression of this protein can weaken the intestinal barrier, letting toxins flow into the body – more commonly known as leaky gut. Mice on the soybean oil diet had decreased levels of the protein and more porous intestinal barriers, raising the risk for inflammation and colitis. “The HNF-4 alpha protein is conserved from mouse to human, so whatever’s happening to it in the context of the mouse gut, there’s a very high chance that a similar effect could be seen in humans as well,” said study coauthor Poonamjot Deol, PhD, an assistant professional researcher at UC Riverside.
Still, Dr. de Silva urges “some caution when interpreting these results,” given that “this is still experimental and needs to be reproduced in clinical studies as humans have a far more varied microbiome and more variable environmental exposures than these very controlled mouse model studies.”
Dr. de Silva says cooking with olive oil can “help increase omega-3 to omega-6 ratios” and advises eating a varied diet that includes omega-3 fats, such as flaxseed and walnuts, and minimal amounts of processed foods and saturated fats.
Looking ahead, endocannabinoids are being explored as “a potential therapy for treating IBD symptoms,” said Dr. Deol. She hopes to delve further into how linoleic acid affects the endocannabinoid system.
A version of this article first appeared on WebMD.com.
FROM GUT MICROBES
Can a biodegradable brain implant deliver lifesaving cancer meds?
It’s the latest advance in a rapidly growing field using ultrasound – high-frequency sound waves undetectable to humans – to fight cancer and other diseases.
The problem addressed by the researchers is the blood-brain barrier, a nearly impenetrable blood vessel lining that keeps harmful molecules from passing into the brain from the blood. But this lining can also block chemo drugs from reaching cancer cells.
So the scientists implanted 1-cm2 devices into the skulls of mice, directly behind the tumor site. The implants generate ultrasound waves, loosening the barrier and allowing the drugs to reach the tumor. The sound waves leave healthy tissue undamaged.
“You inject the drug into the body and turn on the ultrasound at the same time. You’re going to hit precisely at the tumor area every single time you use it,” said lead study author Thanh Nguyen, PhD, an associate professor of mechanical engineering at the University of Connecticut, Storrs.
The drug used in the study was paclitaxel, which normally struggles to get through the blood-brain barrier. The tumors shrank, and the mice doubled their lifetime, compared with untreated mice. The mice showed no bad health effects 6 months later.
Breaking through the blood-brain barrier
The biodegradable implant is made of glycine, an amino acid that’s also strongly piezoelectric, meaning it vibrates when subjected to an electrical current. To make it, researchers cultivated glycine crystals, shattered them into pieces, and finally used a process called electrospinning, which applies a high electrical voltage to the nanocrystals.
Voltage flows to the implant via an external device. The resulting ultrasound causes the tightly adhered cells of the blood-brain barrier to vibrate, stretching them out and creating space for pores to form.
“That allows in very tiny particles, including chemo drugs,” said Dr. Nguyen.
His earlier biodegradable implant broke apart from the force, but the new glycine implant is more flexible, stable, and highly piezoelectric. It could be implanted after a patient has surgery to remove a brain tumor, to continue treating residual cancer cells. The implant dissolves harmlessly in the body over time, and doctors can control its lifespan.
A new wave of uses for ultrasound
Dr. Nguyen’s study builds on similar efforts, including a recent clinical trial of a nonbiodegradable implant for treating brain tumors. Ultrasound can focus energy on precise targets in the body.
It’s like “using a magnifying glass to focus multiple beams of light on a point and burn a hole in a leaf,” said Neal Kassell, MD, founder and chairman of the Focused Ultrasound Foundation. This approach spares adjacent normal tissue.
Doctors now understand more than 30 ways that ultrasound interacts with tissue – from destroying abnormal tissue to delivering drugs more effectively to stimulating an immune response. A decade ago, only five such interactions were known.
This opens the door for treating “a wide spectrum of medical disorders,” from neurodegenerative diseases like Alzheimer’s and Parkinson’s to difficult-to-treat cancers of the prostate and pancreas, and even addiction, said Dr. Kassell.
Dr. Kassell envisions using focused ultrasound to treat brain tumors as an alternative (or complement) to surgery, chemotherapy, immunotherapy, or radiation therapy. In the meantime, implants have helped show “the effectiveness of opening the blood-brain barrier.”
Dr. Nguyen’s team plans on testing the safety and efficacy of their implant in pigs next. Eventually, Dr. Nguyen hopes to develop a patch with an array of implants to target different areas of the brain.
One study coauthor is cofounder of PiezoBioMembrane and SingleTimeMicroneedles. The other study authors reported no conflicts of interest.
A version of this article originally appeared on WebMD.com.
It’s the latest advance in a rapidly growing field using ultrasound – high-frequency sound waves undetectable to humans – to fight cancer and other diseases.
The problem addressed by the researchers is the blood-brain barrier, a nearly impenetrable blood vessel lining that keeps harmful molecules from passing into the brain from the blood. But this lining can also block chemo drugs from reaching cancer cells.
So the scientists implanted 1-cm2 devices into the skulls of mice, directly behind the tumor site. The implants generate ultrasound waves, loosening the barrier and allowing the drugs to reach the tumor. The sound waves leave healthy tissue undamaged.
“You inject the drug into the body and turn on the ultrasound at the same time. You’re going to hit precisely at the tumor area every single time you use it,” said lead study author Thanh Nguyen, PhD, an associate professor of mechanical engineering at the University of Connecticut, Storrs.
The drug used in the study was paclitaxel, which normally struggles to get through the blood-brain barrier. The tumors shrank, and the mice doubled their lifetime, compared with untreated mice. The mice showed no bad health effects 6 months later.
Breaking through the blood-brain barrier
The biodegradable implant is made of glycine, an amino acid that’s also strongly piezoelectric, meaning it vibrates when subjected to an electrical current. To make it, researchers cultivated glycine crystals, shattered them into pieces, and finally used a process called electrospinning, which applies a high electrical voltage to the nanocrystals.
Voltage flows to the implant via an external device. The resulting ultrasound causes the tightly adhered cells of the blood-brain barrier to vibrate, stretching them out and creating space for pores to form.
“That allows in very tiny particles, including chemo drugs,” said Dr. Nguyen.
His earlier biodegradable implant broke apart from the force, but the new glycine implant is more flexible, stable, and highly piezoelectric. It could be implanted after a patient has surgery to remove a brain tumor, to continue treating residual cancer cells. The implant dissolves harmlessly in the body over time, and doctors can control its lifespan.
A new wave of uses for ultrasound
Dr. Nguyen’s study builds on similar efforts, including a recent clinical trial of a nonbiodegradable implant for treating brain tumors. Ultrasound can focus energy on precise targets in the body.
It’s like “using a magnifying glass to focus multiple beams of light on a point and burn a hole in a leaf,” said Neal Kassell, MD, founder and chairman of the Focused Ultrasound Foundation. This approach spares adjacent normal tissue.
Doctors now understand more than 30 ways that ultrasound interacts with tissue – from destroying abnormal tissue to delivering drugs more effectively to stimulating an immune response. A decade ago, only five such interactions were known.
This opens the door for treating “a wide spectrum of medical disorders,” from neurodegenerative diseases like Alzheimer’s and Parkinson’s to difficult-to-treat cancers of the prostate and pancreas, and even addiction, said Dr. Kassell.
Dr. Kassell envisions using focused ultrasound to treat brain tumors as an alternative (or complement) to surgery, chemotherapy, immunotherapy, or radiation therapy. In the meantime, implants have helped show “the effectiveness of opening the blood-brain barrier.”
Dr. Nguyen’s team plans on testing the safety and efficacy of their implant in pigs next. Eventually, Dr. Nguyen hopes to develop a patch with an array of implants to target different areas of the brain.
One study coauthor is cofounder of PiezoBioMembrane and SingleTimeMicroneedles. The other study authors reported no conflicts of interest.
A version of this article originally appeared on WebMD.com.
It’s the latest advance in a rapidly growing field using ultrasound – high-frequency sound waves undetectable to humans – to fight cancer and other diseases.
The problem addressed by the researchers is the blood-brain barrier, a nearly impenetrable blood vessel lining that keeps harmful molecules from passing into the brain from the blood. But this lining can also block chemo drugs from reaching cancer cells.
So the scientists implanted 1-cm2 devices into the skulls of mice, directly behind the tumor site. The implants generate ultrasound waves, loosening the barrier and allowing the drugs to reach the tumor. The sound waves leave healthy tissue undamaged.
“You inject the drug into the body and turn on the ultrasound at the same time. You’re going to hit precisely at the tumor area every single time you use it,” said lead study author Thanh Nguyen, PhD, an associate professor of mechanical engineering at the University of Connecticut, Storrs.
The drug used in the study was paclitaxel, which normally struggles to get through the blood-brain barrier. The tumors shrank, and the mice doubled their lifetime, compared with untreated mice. The mice showed no bad health effects 6 months later.
Breaking through the blood-brain barrier
The biodegradable implant is made of glycine, an amino acid that’s also strongly piezoelectric, meaning it vibrates when subjected to an electrical current. To make it, researchers cultivated glycine crystals, shattered them into pieces, and finally used a process called electrospinning, which applies a high electrical voltage to the nanocrystals.
Voltage flows to the implant via an external device. The resulting ultrasound causes the tightly adhered cells of the blood-brain barrier to vibrate, stretching them out and creating space for pores to form.
“That allows in very tiny particles, including chemo drugs,” said Dr. Nguyen.
His earlier biodegradable implant broke apart from the force, but the new glycine implant is more flexible, stable, and highly piezoelectric. It could be implanted after a patient has surgery to remove a brain tumor, to continue treating residual cancer cells. The implant dissolves harmlessly in the body over time, and doctors can control its lifespan.
A new wave of uses for ultrasound
Dr. Nguyen’s study builds on similar efforts, including a recent clinical trial of a nonbiodegradable implant for treating brain tumors. Ultrasound can focus energy on precise targets in the body.
It’s like “using a magnifying glass to focus multiple beams of light on a point and burn a hole in a leaf,” said Neal Kassell, MD, founder and chairman of the Focused Ultrasound Foundation. This approach spares adjacent normal tissue.
Doctors now understand more than 30 ways that ultrasound interacts with tissue – from destroying abnormal tissue to delivering drugs more effectively to stimulating an immune response. A decade ago, only five such interactions were known.
This opens the door for treating “a wide spectrum of medical disorders,” from neurodegenerative diseases like Alzheimer’s and Parkinson’s to difficult-to-treat cancers of the prostate and pancreas, and even addiction, said Dr. Kassell.
Dr. Kassell envisions using focused ultrasound to treat brain tumors as an alternative (or complement) to surgery, chemotherapy, immunotherapy, or radiation therapy. In the meantime, implants have helped show “the effectiveness of opening the blood-brain barrier.”
Dr. Nguyen’s team plans on testing the safety and efficacy of their implant in pigs next. Eventually, Dr. Nguyen hopes to develop a patch with an array of implants to target different areas of the brain.
One study coauthor is cofounder of PiezoBioMembrane and SingleTimeMicroneedles. The other study authors reported no conflicts of interest.
A version of this article originally appeared on WebMD.com.
FROM SCIENCE ADVANCES
New melting hydrogel bandage could treat burn wounds faster, with less pain
Surgically debriding burn wounds can be tedious for doctors and excruciating for patients. To change that, bioengineers have created a new hydrogel formula that dissolves rapidly from wound sites, melting off in 6 minutes or less.
“The removal of dressings, with the current standard of care, is very hard and time-consuming. It becomes very painful for the patient. People are screaming, or they’re given a lot of opioids,” said senior author O. Berk Usta, PhD, of the Center for Engineering in Medicine and Surgery at Massachusetts General Hospital, Boston. “Those are the things we wanted to minimize: the pain and the time.”
Although beneficial for all patients, a short, painless bandage change would be a particular boon for younger patients. At the pediatric burns care center at Shriners Hospitals for Children (an MGH partner), researchers “observe a lot of children who go through therapy or treatment after burns,” said Dr. Usta. The team at MGH collaborated with scientists at Tufts University, Boston, with those patients in mind, setting out to create a new hydrogel that would transform burn wound care.
A better bandage
Hydrogels provide cooling relief to burn wounds and maintain a moist environment that can speed healing. There are currently hydrogel sheets and hydrogel-infused dressings, as well as gel that is applied directly to burn wounds before being covered with protective material. These dressings must be replaced frequently to prevent infections, but that can be unbearably painful and drawn out, as dressings often stick to wounds.
Mechanical debridement can be especially difficult for second-degree burn patients, whose wounds may still retain nerve endings. Debridement tends to also remove some healthy tissue and can damage newly formed tissue, slowing down healing.
“It can take up to 2, 3 hours, and it requires multiple people working on it,” said Dr. Usta.
The new hydrogel treatment can be applied directly to a wound and it forms a protective barrier around the site in 15 seconds. The hydrogel is then covered by a protective dressing until it needs to be changed.
“After you take off the protective covering, you add another solution, which dissolves the [hydrogel] dressing, so that it can be easily removed from the burn site,” Dr. Usta said.
The solution dissolves the hydrogel in 4-6 minutes.
Hybrid gels
Many hydrogels currently used for burn wounds feature physically cross-linked molecules. This makes them strong and capable of retaining moisture, but also difficult to dissolve. The researchers used a different approach.
“This is not physical cross-linking like the traditional approaches, but rather, softer covalent bonds between the different molecules. And that’s why, when you bring in another solution, the hydrogel dissolves away,” Dr. Usta said.
The new hydrogels rely on a supramolecular assembly: a network of synthetic polymers whose connections can be reversed more easily, meaning they can be dissolved quickly. Another standout feature of the new hydrogels is their hybrid composition, displaying characteristics of both liquids and solids. The polymers are knitted together into a mesh-like network that enables water retention, with the goal of maintaining the moist environment needed for wound healing.
The supramolecular assembly is also greener, Dr. Usta explained; traditional cross-linking approaches produce a lot of toxic by-products that could harm the environment.
And whereas traditional hydrogels can require a dozen chemistry steps to produce, the new hydrogels are ready after mixing two solutions, Dr. Usta explained. This makes them easy to prepare at bedside, ideal for treating large wounds in the ER or even on battlefields.
When tested in vitro, using skin cells, and in vivo, on mice, the new hydrogels were shown to be safe to use on wounds. Additional studies on mice, as well as large animals, will focus on safety and efficacy, and may be followed by human clinical trials, said Dr. Usta.
“The next phase of the project will be to look at whether these dressings will help wound healing by creating a moist environment,” said Dr. Usta.
The researchers are also exploring how to manufacture individual prewrapped hydrogels that could be applied in a clinical setting – or even in people’s homes. The consumer market is “another possibility,” said Dr. Usta, particularly among patients with “smaller, more superficial burns” or patients whose large burn wounds are still healing once they leave the hospital.
This research was supported by the National Institutes of Health, National Science Foundation, Massachusetts General Hospital Executive Committee on Research Interim Support Fund, and Shriners Hospitals.
A version of this article first appeared on Medscape.com.
Surgically debriding burn wounds can be tedious for doctors and excruciating for patients. To change that, bioengineers have created a new hydrogel formula that dissolves rapidly from wound sites, melting off in 6 minutes or less.
“The removal of dressings, with the current standard of care, is very hard and time-consuming. It becomes very painful for the patient. People are screaming, or they’re given a lot of opioids,” said senior author O. Berk Usta, PhD, of the Center for Engineering in Medicine and Surgery at Massachusetts General Hospital, Boston. “Those are the things we wanted to minimize: the pain and the time.”
Although beneficial for all patients, a short, painless bandage change would be a particular boon for younger patients. At the pediatric burns care center at Shriners Hospitals for Children (an MGH partner), researchers “observe a lot of children who go through therapy or treatment after burns,” said Dr. Usta. The team at MGH collaborated with scientists at Tufts University, Boston, with those patients in mind, setting out to create a new hydrogel that would transform burn wound care.
A better bandage
Hydrogels provide cooling relief to burn wounds and maintain a moist environment that can speed healing. There are currently hydrogel sheets and hydrogel-infused dressings, as well as gel that is applied directly to burn wounds before being covered with protective material. These dressings must be replaced frequently to prevent infections, but that can be unbearably painful and drawn out, as dressings often stick to wounds.
Mechanical debridement can be especially difficult for second-degree burn patients, whose wounds may still retain nerve endings. Debridement tends to also remove some healthy tissue and can damage newly formed tissue, slowing down healing.
“It can take up to 2, 3 hours, and it requires multiple people working on it,” said Dr. Usta.
The new hydrogel treatment can be applied directly to a wound and it forms a protective barrier around the site in 15 seconds. The hydrogel is then covered by a protective dressing until it needs to be changed.
“After you take off the protective covering, you add another solution, which dissolves the [hydrogel] dressing, so that it can be easily removed from the burn site,” Dr. Usta said.
The solution dissolves the hydrogel in 4-6 minutes.
Hybrid gels
Many hydrogels currently used for burn wounds feature physically cross-linked molecules. This makes them strong and capable of retaining moisture, but also difficult to dissolve. The researchers used a different approach.
“This is not physical cross-linking like the traditional approaches, but rather, softer covalent bonds between the different molecules. And that’s why, when you bring in another solution, the hydrogel dissolves away,” Dr. Usta said.
The new hydrogels rely on a supramolecular assembly: a network of synthetic polymers whose connections can be reversed more easily, meaning they can be dissolved quickly. Another standout feature of the new hydrogels is their hybrid composition, displaying characteristics of both liquids and solids. The polymers are knitted together into a mesh-like network that enables water retention, with the goal of maintaining the moist environment needed for wound healing.
The supramolecular assembly is also greener, Dr. Usta explained; traditional cross-linking approaches produce a lot of toxic by-products that could harm the environment.
And whereas traditional hydrogels can require a dozen chemistry steps to produce, the new hydrogels are ready after mixing two solutions, Dr. Usta explained. This makes them easy to prepare at bedside, ideal for treating large wounds in the ER or even on battlefields.
When tested in vitro, using skin cells, and in vivo, on mice, the new hydrogels were shown to be safe to use on wounds. Additional studies on mice, as well as large animals, will focus on safety and efficacy, and may be followed by human clinical trials, said Dr. Usta.
“The next phase of the project will be to look at whether these dressings will help wound healing by creating a moist environment,” said Dr. Usta.
The researchers are also exploring how to manufacture individual prewrapped hydrogels that could be applied in a clinical setting – or even in people’s homes. The consumer market is “another possibility,” said Dr. Usta, particularly among patients with “smaller, more superficial burns” or patients whose large burn wounds are still healing once they leave the hospital.
This research was supported by the National Institutes of Health, National Science Foundation, Massachusetts General Hospital Executive Committee on Research Interim Support Fund, and Shriners Hospitals.
A version of this article first appeared on Medscape.com.
Surgically debriding burn wounds can be tedious for doctors and excruciating for patients. To change that, bioengineers have created a new hydrogel formula that dissolves rapidly from wound sites, melting off in 6 minutes or less.
“The removal of dressings, with the current standard of care, is very hard and time-consuming. It becomes very painful for the patient. People are screaming, or they’re given a lot of opioids,” said senior author O. Berk Usta, PhD, of the Center for Engineering in Medicine and Surgery at Massachusetts General Hospital, Boston. “Those are the things we wanted to minimize: the pain and the time.”
Although beneficial for all patients, a short, painless bandage change would be a particular boon for younger patients. At the pediatric burns care center at Shriners Hospitals for Children (an MGH partner), researchers “observe a lot of children who go through therapy or treatment after burns,” said Dr. Usta. The team at MGH collaborated with scientists at Tufts University, Boston, with those patients in mind, setting out to create a new hydrogel that would transform burn wound care.
A better bandage
Hydrogels provide cooling relief to burn wounds and maintain a moist environment that can speed healing. There are currently hydrogel sheets and hydrogel-infused dressings, as well as gel that is applied directly to burn wounds before being covered with protective material. These dressings must be replaced frequently to prevent infections, but that can be unbearably painful and drawn out, as dressings often stick to wounds.
Mechanical debridement can be especially difficult for second-degree burn patients, whose wounds may still retain nerve endings. Debridement tends to also remove some healthy tissue and can damage newly formed tissue, slowing down healing.
“It can take up to 2, 3 hours, and it requires multiple people working on it,” said Dr. Usta.
The new hydrogel treatment can be applied directly to a wound and it forms a protective barrier around the site in 15 seconds. The hydrogel is then covered by a protective dressing until it needs to be changed.
“After you take off the protective covering, you add another solution, which dissolves the [hydrogel] dressing, so that it can be easily removed from the burn site,” Dr. Usta said.
The solution dissolves the hydrogel in 4-6 minutes.
Hybrid gels
Many hydrogels currently used for burn wounds feature physically cross-linked molecules. This makes them strong and capable of retaining moisture, but also difficult to dissolve. The researchers used a different approach.
“This is not physical cross-linking like the traditional approaches, but rather, softer covalent bonds between the different molecules. And that’s why, when you bring in another solution, the hydrogel dissolves away,” Dr. Usta said.
The new hydrogels rely on a supramolecular assembly: a network of synthetic polymers whose connections can be reversed more easily, meaning they can be dissolved quickly. Another standout feature of the new hydrogels is their hybrid composition, displaying characteristics of both liquids and solids. The polymers are knitted together into a mesh-like network that enables water retention, with the goal of maintaining the moist environment needed for wound healing.
The supramolecular assembly is also greener, Dr. Usta explained; traditional cross-linking approaches produce a lot of toxic by-products that could harm the environment.
And whereas traditional hydrogels can require a dozen chemistry steps to produce, the new hydrogels are ready after mixing two solutions, Dr. Usta explained. This makes them easy to prepare at bedside, ideal for treating large wounds in the ER or even on battlefields.
When tested in vitro, using skin cells, and in vivo, on mice, the new hydrogels were shown to be safe to use on wounds. Additional studies on mice, as well as large animals, will focus on safety and efficacy, and may be followed by human clinical trials, said Dr. Usta.
“The next phase of the project will be to look at whether these dressings will help wound healing by creating a moist environment,” said Dr. Usta.
The researchers are also exploring how to manufacture individual prewrapped hydrogels that could be applied in a clinical setting – or even in people’s homes. The consumer market is “another possibility,” said Dr. Usta, particularly among patients with “smaller, more superficial burns” or patients whose large burn wounds are still healing once they leave the hospital.
This research was supported by the National Institutes of Health, National Science Foundation, Massachusetts General Hospital Executive Committee on Research Interim Support Fund, and Shriners Hospitals.
A version of this article first appeared on Medscape.com.
FROM BIOACTIVE MATERIALS
New electrodes made of sugar more effectively monitor mom’s health
A new type of electrode made from sugar could help doctors and researchers more effectively monitor contractions during preterm labor, a condition that precedes almost half of preterm births and is the leading cause of U.S. neonatal deaths.
The sensors, developed by engineers at the McKelvey School of Engineering at Washington University, St. Louis, could help us understand why some patients experience preterm labor, improve medical interventions, and save lives. In the experiment, the researchers built an array of the new electrodes and successfully tested it on a pregnant person in a lab.
The goal is a home-monitoring belt that is comfortable enough for patients to wear and accurate enough to be clinically useful. Built off a framework of sugar and conductive polymers, the thin electrodes have a sponge-like quality that allows them to hold more gel than standard electrodes, measure for 3 hours instead of 1, and resist artifacts created by patient movement. When tested on a pregnant woman, the new electrodes picked up clean signals even when the patient moved, said electrical engineer and article co-author Chuan Wang, PhD.
There is current technology that exists to monitor and map contractions during early labor, but the tests require hundreds of wire electrodes. Patients must sit still for half an hour while the electrodes are applied, then remain immobile for the test itself, which has a high sensitivity to movement.
“It’s very uncomfortable. In the clinical setting, the recording typically lasts for 15 minutes to half an hour. During that time, doctors want the patient to be still,” said Dr. Wang. “If the patient has to move, it’s going to introduce some artifacts, which is going to ruin the imaging process.”
Dr. Wang and colleagues wanted to develop an inexpensive new electrode that would be more comfortable for patients to wear for longer periods of time, yet sensitive enough to detect electrical signals in the body during preterm labor.
To do this, they used sugar structures to create a pliable electrode with a spongy structure. The new electrodes have micropores that hold conductive gel, increasing the amount of electrified surface area touching the skin.
“With the porous structure, we are effectively increasing the area by many, many times,” Dr. Wang said. “Because all those voids also contact the skin, increasing the contact area can boost the strength of the signal.”
With conventional electrodes, the gel dries quickly on the flat surface, causing signal quality to plummet. But the new electrodes can be used for “many hours” before drying out, according to Dr. Wang.
Additionally, the soft material of the new electrode acts “like a buffer” that absorbs motion and prevents the electrode from sliding around, according to Dr. Wang. That means patients can move while wearing the spongy electrodes without disturbing the recording of electrical signals in the body.
From sugar cube to spongy electrode
To create the new electrode, the researchers began by molding sugar into an electrode-shaped template. The template was then dipped into a liquid polymer, which oozed in between the grains of sugar. Next, the template underwent oven curing, emerging as a solid yet spongy structure. Hot water was then applied to dissolve the sugar.
The sugar structure is useful here because of the negative space around the grains, which is filled by the polymer – and then because of the negative space left when the sugar dissolves.
“When the sugar grains are removed, that’s where the pores are located,” Dr. Wang explained.
The sponge surface was then converted from hydrophobic to hydrophilic, thanks to an oxygen plasma treatment. Next, the sponge was blanketed in a layer of conductive polymer – a liquid that Dr. Wang likens to black ink – transforming it into an electrode. (Without the oxygen plasma step, the sponge wouldn’t have absorbed the conductive material.) After another oven-curing session, the device was affixed with wires and ready to be used.
The researchers are continuing to refine the concept and hope to develop a wireless wearable device with many spongy electrodes that record signals simultaneously – and that patients can use at home.
In addition to monitoring maternal and fetal health during labor, the researchers say the belt-like device could be used for other types of imaging and diagnosis.
“Depending on the scenario, different signals can be recorded,” Dr. Wang said. “It could be an EMG for a pregnant woman, or an ECG for an athlete or a patient with chronic cardiovascular disease that needs monitoring.”
This work was funded by the Bill & Melinda Gates Foundation (INV-005417, INV-035476). The authors acknowledge the Washington University in St. Louis Institute of Materials Science and Engineering for the use of instruments and staff assistance.
A version of this article first appeared on Medscape.com.
A new type of electrode made from sugar could help doctors and researchers more effectively monitor contractions during preterm labor, a condition that precedes almost half of preterm births and is the leading cause of U.S. neonatal deaths.
The sensors, developed by engineers at the McKelvey School of Engineering at Washington University, St. Louis, could help us understand why some patients experience preterm labor, improve medical interventions, and save lives. In the experiment, the researchers built an array of the new electrodes and successfully tested it on a pregnant person in a lab.
The goal is a home-monitoring belt that is comfortable enough for patients to wear and accurate enough to be clinically useful. Built off a framework of sugar and conductive polymers, the thin electrodes have a sponge-like quality that allows them to hold more gel than standard electrodes, measure for 3 hours instead of 1, and resist artifacts created by patient movement. When tested on a pregnant woman, the new electrodes picked up clean signals even when the patient moved, said electrical engineer and article co-author Chuan Wang, PhD.
There is current technology that exists to monitor and map contractions during early labor, but the tests require hundreds of wire electrodes. Patients must sit still for half an hour while the electrodes are applied, then remain immobile for the test itself, which has a high sensitivity to movement.
“It’s very uncomfortable. In the clinical setting, the recording typically lasts for 15 minutes to half an hour. During that time, doctors want the patient to be still,” said Dr. Wang. “If the patient has to move, it’s going to introduce some artifacts, which is going to ruin the imaging process.”
Dr. Wang and colleagues wanted to develop an inexpensive new electrode that would be more comfortable for patients to wear for longer periods of time, yet sensitive enough to detect electrical signals in the body during preterm labor.
To do this, they used sugar structures to create a pliable electrode with a spongy structure. The new electrodes have micropores that hold conductive gel, increasing the amount of electrified surface area touching the skin.
“With the porous structure, we are effectively increasing the area by many, many times,” Dr. Wang said. “Because all those voids also contact the skin, increasing the contact area can boost the strength of the signal.”
With conventional electrodes, the gel dries quickly on the flat surface, causing signal quality to plummet. But the new electrodes can be used for “many hours” before drying out, according to Dr. Wang.
Additionally, the soft material of the new electrode acts “like a buffer” that absorbs motion and prevents the electrode from sliding around, according to Dr. Wang. That means patients can move while wearing the spongy electrodes without disturbing the recording of electrical signals in the body.
From sugar cube to spongy electrode
To create the new electrode, the researchers began by molding sugar into an electrode-shaped template. The template was then dipped into a liquid polymer, which oozed in between the grains of sugar. Next, the template underwent oven curing, emerging as a solid yet spongy structure. Hot water was then applied to dissolve the sugar.
The sugar structure is useful here because of the negative space around the grains, which is filled by the polymer – and then because of the negative space left when the sugar dissolves.
“When the sugar grains are removed, that’s where the pores are located,” Dr. Wang explained.
The sponge surface was then converted from hydrophobic to hydrophilic, thanks to an oxygen plasma treatment. Next, the sponge was blanketed in a layer of conductive polymer – a liquid that Dr. Wang likens to black ink – transforming it into an electrode. (Without the oxygen plasma step, the sponge wouldn’t have absorbed the conductive material.) After another oven-curing session, the device was affixed with wires and ready to be used.
The researchers are continuing to refine the concept and hope to develop a wireless wearable device with many spongy electrodes that record signals simultaneously – and that patients can use at home.
In addition to monitoring maternal and fetal health during labor, the researchers say the belt-like device could be used for other types of imaging and diagnosis.
“Depending on the scenario, different signals can be recorded,” Dr. Wang said. “It could be an EMG for a pregnant woman, or an ECG for an athlete or a patient with chronic cardiovascular disease that needs monitoring.”
This work was funded by the Bill & Melinda Gates Foundation (INV-005417, INV-035476). The authors acknowledge the Washington University in St. Louis Institute of Materials Science and Engineering for the use of instruments and staff assistance.
A version of this article first appeared on Medscape.com.
A new type of electrode made from sugar could help doctors and researchers more effectively monitor contractions during preterm labor, a condition that precedes almost half of preterm births and is the leading cause of U.S. neonatal deaths.
The sensors, developed by engineers at the McKelvey School of Engineering at Washington University, St. Louis, could help us understand why some patients experience preterm labor, improve medical interventions, and save lives. In the experiment, the researchers built an array of the new electrodes and successfully tested it on a pregnant person in a lab.
The goal is a home-monitoring belt that is comfortable enough for patients to wear and accurate enough to be clinically useful. Built off a framework of sugar and conductive polymers, the thin electrodes have a sponge-like quality that allows them to hold more gel than standard electrodes, measure for 3 hours instead of 1, and resist artifacts created by patient movement. When tested on a pregnant woman, the new electrodes picked up clean signals even when the patient moved, said electrical engineer and article co-author Chuan Wang, PhD.
There is current technology that exists to monitor and map contractions during early labor, but the tests require hundreds of wire electrodes. Patients must sit still for half an hour while the electrodes are applied, then remain immobile for the test itself, which has a high sensitivity to movement.
“It’s very uncomfortable. In the clinical setting, the recording typically lasts for 15 minutes to half an hour. During that time, doctors want the patient to be still,” said Dr. Wang. “If the patient has to move, it’s going to introduce some artifacts, which is going to ruin the imaging process.”
Dr. Wang and colleagues wanted to develop an inexpensive new electrode that would be more comfortable for patients to wear for longer periods of time, yet sensitive enough to detect electrical signals in the body during preterm labor.
To do this, they used sugar structures to create a pliable electrode with a spongy structure. The new electrodes have micropores that hold conductive gel, increasing the amount of electrified surface area touching the skin.
“With the porous structure, we are effectively increasing the area by many, many times,” Dr. Wang said. “Because all those voids also contact the skin, increasing the contact area can boost the strength of the signal.”
With conventional electrodes, the gel dries quickly on the flat surface, causing signal quality to plummet. But the new electrodes can be used for “many hours” before drying out, according to Dr. Wang.
Additionally, the soft material of the new electrode acts “like a buffer” that absorbs motion and prevents the electrode from sliding around, according to Dr. Wang. That means patients can move while wearing the spongy electrodes without disturbing the recording of electrical signals in the body.
From sugar cube to spongy electrode
To create the new electrode, the researchers began by molding sugar into an electrode-shaped template. The template was then dipped into a liquid polymer, which oozed in between the grains of sugar. Next, the template underwent oven curing, emerging as a solid yet spongy structure. Hot water was then applied to dissolve the sugar.
The sugar structure is useful here because of the negative space around the grains, which is filled by the polymer – and then because of the negative space left when the sugar dissolves.
“When the sugar grains are removed, that’s where the pores are located,” Dr. Wang explained.
The sponge surface was then converted from hydrophobic to hydrophilic, thanks to an oxygen plasma treatment. Next, the sponge was blanketed in a layer of conductive polymer – a liquid that Dr. Wang likens to black ink – transforming it into an electrode. (Without the oxygen plasma step, the sponge wouldn’t have absorbed the conductive material.) After another oven-curing session, the device was affixed with wires and ready to be used.
The researchers are continuing to refine the concept and hope to develop a wireless wearable device with many spongy electrodes that record signals simultaneously – and that patients can use at home.
In addition to monitoring maternal and fetal health during labor, the researchers say the belt-like device could be used for other types of imaging and diagnosis.
“Depending on the scenario, different signals can be recorded,” Dr. Wang said. “It could be an EMG for a pregnant woman, or an ECG for an athlete or a patient with chronic cardiovascular disease that needs monitoring.”
This work was funded by the Bill & Melinda Gates Foundation (INV-005417, INV-035476). The authors acknowledge the Washington University in St. Louis Institute of Materials Science and Engineering for the use of instruments and staff assistance.
A version of this article first appeared on Medscape.com.