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FDA OKs symplicity renal denervation system for hypertension
the company has announced.
The Symplicity Spyral system, also known as the Symplicity blood pressure procedure, provides a catheter-based approach to denervate the renal arteries using radiofrequency energy.
Back in August, the FDA’s Circulatory System Devices Panel unanimously agreed that the Symplicity Spyral system is safe, but the panel was split on its efficacy and whether the benefits outweighed the risks associated with its use.
As part of the Medtronic SPYRAL HTN Global Clinical Program, more than 25,000 patients have been treated worldwide, both in the presence and absence of medication, and in patients with high baseline cardiovascular risk.
The SPYRAL HTN-OFF study enrolled patients with hypertension whose medications could be stopped at the start of the trial.
The primary effectiveness endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure (ASBP) from baseline to 3 months after renal denervation or sham procedure. The study showed a statistically significant reduction of 3.9 mm Hg ASBP in patients who received the device, compared with sham-control patients.
The SPYRAL HTN-ON study evaluated patients with uncontrolled hypertension who continued taking their BP medications during treatment with either the Spyral renal denervation device or a sham device.
The primary endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure at 6 months. The study showed a nonsignificant 24-hour 0.03 mm Hg reduction in ASBP in active-treatment patients, compared with sham-control patients.
“The Symplicity blood pressure procedure is safe and effective, providing significant ‘always-on’ blood pressure reductions for patients,” David Kandzari, MD, chief, Piedmont Heart Institute, Atlanta, and co–principal investigator of the SPYRAL clinical program, said in the news release.
“This approval paves the way for a transformation in hypertension treatment, offering a solution that complements medication and lifestyle changes,” added co–principal investigator Raymond Townsend, MD, with University of Pennsylvania, Philadelphia.
Medtronic notes that patient preference and shared decision-making are key components when considering the Symplicity blood pressure procedure.
In a patient preference study led by Medtronic, when presented with an interventional treatment with BP reduction and potential risks in line with those of the Symplicity blood pressure procedure, approximately one-third of patients were likely to choose the interventional treatment.
Earlier in November, the FDA also approved the Paradise Ultrasound Renal Denervation system (Recor Medical, Otsuka Medical Devices) for the treatment of hypertension.
A version of this article first appeared on Medscape.com.
the company has announced.
The Symplicity Spyral system, also known as the Symplicity blood pressure procedure, provides a catheter-based approach to denervate the renal arteries using radiofrequency energy.
Back in August, the FDA’s Circulatory System Devices Panel unanimously agreed that the Symplicity Spyral system is safe, but the panel was split on its efficacy and whether the benefits outweighed the risks associated with its use.
As part of the Medtronic SPYRAL HTN Global Clinical Program, more than 25,000 patients have been treated worldwide, both in the presence and absence of medication, and in patients with high baseline cardiovascular risk.
The SPYRAL HTN-OFF study enrolled patients with hypertension whose medications could be stopped at the start of the trial.
The primary effectiveness endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure (ASBP) from baseline to 3 months after renal denervation or sham procedure. The study showed a statistically significant reduction of 3.9 mm Hg ASBP in patients who received the device, compared with sham-control patients.
The SPYRAL HTN-ON study evaluated patients with uncontrolled hypertension who continued taking their BP medications during treatment with either the Spyral renal denervation device or a sham device.
The primary endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure at 6 months. The study showed a nonsignificant 24-hour 0.03 mm Hg reduction in ASBP in active-treatment patients, compared with sham-control patients.
“The Symplicity blood pressure procedure is safe and effective, providing significant ‘always-on’ blood pressure reductions for patients,” David Kandzari, MD, chief, Piedmont Heart Institute, Atlanta, and co–principal investigator of the SPYRAL clinical program, said in the news release.
“This approval paves the way for a transformation in hypertension treatment, offering a solution that complements medication and lifestyle changes,” added co–principal investigator Raymond Townsend, MD, with University of Pennsylvania, Philadelphia.
Medtronic notes that patient preference and shared decision-making are key components when considering the Symplicity blood pressure procedure.
In a patient preference study led by Medtronic, when presented with an interventional treatment with BP reduction and potential risks in line with those of the Symplicity blood pressure procedure, approximately one-third of patients were likely to choose the interventional treatment.
Earlier in November, the FDA also approved the Paradise Ultrasound Renal Denervation system (Recor Medical, Otsuka Medical Devices) for the treatment of hypertension.
A version of this article first appeared on Medscape.com.
the company has announced.
The Symplicity Spyral system, also known as the Symplicity blood pressure procedure, provides a catheter-based approach to denervate the renal arteries using radiofrequency energy.
Back in August, the FDA’s Circulatory System Devices Panel unanimously agreed that the Symplicity Spyral system is safe, but the panel was split on its efficacy and whether the benefits outweighed the risks associated with its use.
As part of the Medtronic SPYRAL HTN Global Clinical Program, more than 25,000 patients have been treated worldwide, both in the presence and absence of medication, and in patients with high baseline cardiovascular risk.
The SPYRAL HTN-OFF study enrolled patients with hypertension whose medications could be stopped at the start of the trial.
The primary effectiveness endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure (ASBP) from baseline to 3 months after renal denervation or sham procedure. The study showed a statistically significant reduction of 3.9 mm Hg ASBP in patients who received the device, compared with sham-control patients.
The SPYRAL HTN-ON study evaluated patients with uncontrolled hypertension who continued taking their BP medications during treatment with either the Spyral renal denervation device or a sham device.
The primary endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure at 6 months. The study showed a nonsignificant 24-hour 0.03 mm Hg reduction in ASBP in active-treatment patients, compared with sham-control patients.
“The Symplicity blood pressure procedure is safe and effective, providing significant ‘always-on’ blood pressure reductions for patients,” David Kandzari, MD, chief, Piedmont Heart Institute, Atlanta, and co–principal investigator of the SPYRAL clinical program, said in the news release.
“This approval paves the way for a transformation in hypertension treatment, offering a solution that complements medication and lifestyle changes,” added co–principal investigator Raymond Townsend, MD, with University of Pennsylvania, Philadelphia.
Medtronic notes that patient preference and shared decision-making are key components when considering the Symplicity blood pressure procedure.
In a patient preference study led by Medtronic, when presented with an interventional treatment with BP reduction and potential risks in line with those of the Symplicity blood pressure procedure, approximately one-third of patients were likely to choose the interventional treatment.
Earlier in November, the FDA also approved the Paradise Ultrasound Renal Denervation system (Recor Medical, Otsuka Medical Devices) for the treatment of hypertension.
A version of this article first appeared on Medscape.com.
PREVENT: AHA’s new risk calculator incorporates CKM health
.
The new Predicting Risk of CVD Events (PREVENT) calculator is the first risk calculator that combines measures of cardiovascular, kidney, and metabolic health to estimate risk for CVD.
It follows an AHA presidential advisory and scientific statement published in October, formally defining cardiovascular-kidney-metabolic (CKM) syndrome.
The PREVENT calculator also “starts earlier and goes longer” than the pooled cohort equations (PCE), Sadiya Khan, MD, MSc, chair of the statement writing committee, told this news organization.
PREVENT is for use in adults aged 30-79 years and estimates the 10- and 30-year risk of total CVD including, for the first time, heart failure. The PCE were designed to assess 10-year risk of only myocardial infarction and stroke and only in adults aged 40-79 years.
“The new PREVENT equations are important for doctors because they allow us to start conversations earlier and more comprehensively and accurately calculate risk for our patients,” said Dr. Khan, preventive cardiologist at Northwestern Medicine and associate professor at Northwestern University in Chicago.
“We want to support clinicians in starting these conversations around optimizing CKM health earlier and begin to engage in discussions on ways to optimize health,” Dr. Khan added.
The AHA scientific statement on the PREVENT calculator, with Dr. Khan as lead author, was published online in Circulation, with an accompanying article that describes development and validation of the tool.
Going beyond the PCE
The new calculator was developed using health information from more than 6 million adults from diverse racial and ethnic, socioeconomic, and geographic backgrounds.
In addition to blood pressure and cholesterol levels, the PREVENT equations allow for inclusion of hemoglobin A1c, if necessary, to monitor metabolic health.
It also includes estimated glomerular filtration rate (eGFR), a measure of kidney function, and allows for use of albumin excretion to monitor kidney disease to further individualize risk assessment and help inform personalized treatment options.
The new calculator also asks about tobacco use and use of medications for CVD risk factors and factors in age and sex, and it removes race from the risk calculations.
“The inclusion of race in risk prediction may imply that differences by race are not modifiable and may reify race as a biological construct, which may worsen health disparities. Therefore, it was decided a priori not to include race as a predictor in the development of PREVENT,” the writing group said.
They emphasized that the PREVENT calculator has similar accuracy among varied racial and ethnic groups.
The equations include an option to use the Social Deprivation Index, which incorporates measures of adverse social determinants of health such as education, poverty, unemployment, and factors based on a person’s environment.
The PREVENT equations are a “critical first step” toward including CKM health and social factors in risk prediction for CVD, Dr. Khan said in a news release.
“We are working on finalizing the online tool and it should be available soon – hopefully in a few weeks,” Dr. Khan told this news organization.
Knowledge gaps
The scientific statement lists several knowledge gaps and areas for more research. These include:
- Incorporating “net benefit” to identify the expected benefit of treatment recommendations based on an individual’s level of risk.
- Collecting more data from people of diverse race and ethnic backgrounds to better represent the increasing diversity in the United States. The number of Hispanic and Asian people included in the PREVENT datasets is lower than national estimates in the general U.S. population, so risk estimations in these populations may be less precise.
- Expanding the collection, reporting, and standardization of social determinants of health data, such as individual information rather than neighborhood information.
- Expanding risk assessment and prevention to earlier in life (childhood and/or adolescence) and in key life periods, such as during the peripartum period, since adverse pregnancy outcomes are associated with increased CVD risk.
- Investigating whether predicting adverse kidney outcomes, particularly among people with and without type 2 diabetes, may further optimize cardiovascular risk prediction.
The scientific statement was prepared by the volunteer writing group on behalf of the AHA. Dr. Khan reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
.
The new Predicting Risk of CVD Events (PREVENT) calculator is the first risk calculator that combines measures of cardiovascular, kidney, and metabolic health to estimate risk for CVD.
It follows an AHA presidential advisory and scientific statement published in October, formally defining cardiovascular-kidney-metabolic (CKM) syndrome.
The PREVENT calculator also “starts earlier and goes longer” than the pooled cohort equations (PCE), Sadiya Khan, MD, MSc, chair of the statement writing committee, told this news organization.
PREVENT is for use in adults aged 30-79 years and estimates the 10- and 30-year risk of total CVD including, for the first time, heart failure. The PCE were designed to assess 10-year risk of only myocardial infarction and stroke and only in adults aged 40-79 years.
“The new PREVENT equations are important for doctors because they allow us to start conversations earlier and more comprehensively and accurately calculate risk for our patients,” said Dr. Khan, preventive cardiologist at Northwestern Medicine and associate professor at Northwestern University in Chicago.
“We want to support clinicians in starting these conversations around optimizing CKM health earlier and begin to engage in discussions on ways to optimize health,” Dr. Khan added.
The AHA scientific statement on the PREVENT calculator, with Dr. Khan as lead author, was published online in Circulation, with an accompanying article that describes development and validation of the tool.
Going beyond the PCE
The new calculator was developed using health information from more than 6 million adults from diverse racial and ethnic, socioeconomic, and geographic backgrounds.
In addition to blood pressure and cholesterol levels, the PREVENT equations allow for inclusion of hemoglobin A1c, if necessary, to monitor metabolic health.
It also includes estimated glomerular filtration rate (eGFR), a measure of kidney function, and allows for use of albumin excretion to monitor kidney disease to further individualize risk assessment and help inform personalized treatment options.
The new calculator also asks about tobacco use and use of medications for CVD risk factors and factors in age and sex, and it removes race from the risk calculations.
“The inclusion of race in risk prediction may imply that differences by race are not modifiable and may reify race as a biological construct, which may worsen health disparities. Therefore, it was decided a priori not to include race as a predictor in the development of PREVENT,” the writing group said.
They emphasized that the PREVENT calculator has similar accuracy among varied racial and ethnic groups.
The equations include an option to use the Social Deprivation Index, which incorporates measures of adverse social determinants of health such as education, poverty, unemployment, and factors based on a person’s environment.
The PREVENT equations are a “critical first step” toward including CKM health and social factors in risk prediction for CVD, Dr. Khan said in a news release.
“We are working on finalizing the online tool and it should be available soon – hopefully in a few weeks,” Dr. Khan told this news organization.
Knowledge gaps
The scientific statement lists several knowledge gaps and areas for more research. These include:
- Incorporating “net benefit” to identify the expected benefit of treatment recommendations based on an individual’s level of risk.
- Collecting more data from people of diverse race and ethnic backgrounds to better represent the increasing diversity in the United States. The number of Hispanic and Asian people included in the PREVENT datasets is lower than national estimates in the general U.S. population, so risk estimations in these populations may be less precise.
- Expanding the collection, reporting, and standardization of social determinants of health data, such as individual information rather than neighborhood information.
- Expanding risk assessment and prevention to earlier in life (childhood and/or adolescence) and in key life periods, such as during the peripartum period, since adverse pregnancy outcomes are associated with increased CVD risk.
- Investigating whether predicting adverse kidney outcomes, particularly among people with and without type 2 diabetes, may further optimize cardiovascular risk prediction.
The scientific statement was prepared by the volunteer writing group on behalf of the AHA. Dr. Khan reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
.
The new Predicting Risk of CVD Events (PREVENT) calculator is the first risk calculator that combines measures of cardiovascular, kidney, and metabolic health to estimate risk for CVD.
It follows an AHA presidential advisory and scientific statement published in October, formally defining cardiovascular-kidney-metabolic (CKM) syndrome.
The PREVENT calculator also “starts earlier and goes longer” than the pooled cohort equations (PCE), Sadiya Khan, MD, MSc, chair of the statement writing committee, told this news organization.
PREVENT is for use in adults aged 30-79 years and estimates the 10- and 30-year risk of total CVD including, for the first time, heart failure. The PCE were designed to assess 10-year risk of only myocardial infarction and stroke and only in adults aged 40-79 years.
“The new PREVENT equations are important for doctors because they allow us to start conversations earlier and more comprehensively and accurately calculate risk for our patients,” said Dr. Khan, preventive cardiologist at Northwestern Medicine and associate professor at Northwestern University in Chicago.
“We want to support clinicians in starting these conversations around optimizing CKM health earlier and begin to engage in discussions on ways to optimize health,” Dr. Khan added.
The AHA scientific statement on the PREVENT calculator, with Dr. Khan as lead author, was published online in Circulation, with an accompanying article that describes development and validation of the tool.
Going beyond the PCE
The new calculator was developed using health information from more than 6 million adults from diverse racial and ethnic, socioeconomic, and geographic backgrounds.
In addition to blood pressure and cholesterol levels, the PREVENT equations allow for inclusion of hemoglobin A1c, if necessary, to monitor metabolic health.
It also includes estimated glomerular filtration rate (eGFR), a measure of kidney function, and allows for use of albumin excretion to monitor kidney disease to further individualize risk assessment and help inform personalized treatment options.
The new calculator also asks about tobacco use and use of medications for CVD risk factors and factors in age and sex, and it removes race from the risk calculations.
“The inclusion of race in risk prediction may imply that differences by race are not modifiable and may reify race as a biological construct, which may worsen health disparities. Therefore, it was decided a priori not to include race as a predictor in the development of PREVENT,” the writing group said.
They emphasized that the PREVENT calculator has similar accuracy among varied racial and ethnic groups.
The equations include an option to use the Social Deprivation Index, which incorporates measures of adverse social determinants of health such as education, poverty, unemployment, and factors based on a person’s environment.
The PREVENT equations are a “critical first step” toward including CKM health and social factors in risk prediction for CVD, Dr. Khan said in a news release.
“We are working on finalizing the online tool and it should be available soon – hopefully in a few weeks,” Dr. Khan told this news organization.
Knowledge gaps
The scientific statement lists several knowledge gaps and areas for more research. These include:
- Incorporating “net benefit” to identify the expected benefit of treatment recommendations based on an individual’s level of risk.
- Collecting more data from people of diverse race and ethnic backgrounds to better represent the increasing diversity in the United States. The number of Hispanic and Asian people included in the PREVENT datasets is lower than national estimates in the general U.S. population, so risk estimations in these populations may be less precise.
- Expanding the collection, reporting, and standardization of social determinants of health data, such as individual information rather than neighborhood information.
- Expanding risk assessment and prevention to earlier in life (childhood and/or adolescence) and in key life periods, such as during the peripartum period, since adverse pregnancy outcomes are associated with increased CVD risk.
- Investigating whether predicting adverse kidney outcomes, particularly among people with and without type 2 diabetes, may further optimize cardiovascular risk prediction.
The scientific statement was prepared by the volunteer writing group on behalf of the AHA. Dr. Khan reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CIRCULATION
Can a Mediterranean diet reduce breast cancer recurrence?
TOPLINE:
However, women at high risk for recurrence who made the greatest improvements in their diet quality demonstrated a 41% lower risk for recurrence, compared with peers who made the fewest improvements.
METHODOLOGY:
- A growing body of evidence suggests that a better dietary quality may improve survival among patients with breast cancer, but whether diet impacts breast cancer–specific mortality remains controversial.
- To better understand the relationship between diet and breast cancer outcomes, investigators recruited 1,542 women with breast cancer who had undergone surgical resection in the past 5 years and were considered high risk for recurrence.
- All women received general recommendations for cancer prevention, while the intervention group received active support to adhere to a macro–Mediterranean-style diet, which encourages mainly consuming whole grains, legumes, and high-fiber vegetables and discourages eating foods high in saturated and trans fats, processed meats, and foods and beverages high in sugar.
- Diet was assessed at baseline, 1 year, and every few months in subsequent years via food frequency diaries. Compliance with dietary recommendations for the whole cohort was assessed using a dietary index developed for the trial.
- In addition to diet, women in the diet intervention group were encouraged to maintain moderate to intense physical activity – 30 minutes, on average, each day – and received pedometers to track steps, aiming for 10,000 per day.
TAKEAWAY:
- Over 5 years of follow-up, the rate of breast cancer recurrence did not differ between women in the diet intervention group and those in the control group. Overall, 95 of 769 women in the intervention group and 98 of 773 in the control group had a breast cancer recurrence (hazard ratio, 0.99).
- When evaluating outcomes in the entire cohort, looking at everyone’s level of compliance with dietary recommendations, women who adhered the most to the dietary guidelines had a 41% lower recurrence risk compared with women who adhered the least (HR, 0.59).
- The greatest protective effect among women who demonstrated high compliance occurred in those with ER-positive cancers (HR, 0.42) and those with ER-positive cancers who received tamoxifen (HR, 0.30).
IN PRACTICE:
This intervention trial “did not confirm the hypothesis that a comprehensive dietary modification reduces breast cancer recurrence and metastases,” but when looking at compliance to the Mediterranean diet overall, the analysis did find “a significantly better prognosis” for women with the best adherence.
SOURCE:
The study, with first author Franco Berrino, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, was published online in Clinical Cancer Research.
LIMITATIONS:
The study relied on self-reported dietary data. No dietary instrument was used to estimate nutrient intake and the dietary index developed for the trial remains unvalidated.
DISCLOSURES:
The study was supported by the Italian Department of Health, the Associazione Italiana per la Ricerca sul Cancro, and the Vita e Salute Foundation. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
However, women at high risk for recurrence who made the greatest improvements in their diet quality demonstrated a 41% lower risk for recurrence, compared with peers who made the fewest improvements.
METHODOLOGY:
- A growing body of evidence suggests that a better dietary quality may improve survival among patients with breast cancer, but whether diet impacts breast cancer–specific mortality remains controversial.
- To better understand the relationship between diet and breast cancer outcomes, investigators recruited 1,542 women with breast cancer who had undergone surgical resection in the past 5 years and were considered high risk for recurrence.
- All women received general recommendations for cancer prevention, while the intervention group received active support to adhere to a macro–Mediterranean-style diet, which encourages mainly consuming whole grains, legumes, and high-fiber vegetables and discourages eating foods high in saturated and trans fats, processed meats, and foods and beverages high in sugar.
- Diet was assessed at baseline, 1 year, and every few months in subsequent years via food frequency diaries. Compliance with dietary recommendations for the whole cohort was assessed using a dietary index developed for the trial.
- In addition to diet, women in the diet intervention group were encouraged to maintain moderate to intense physical activity – 30 minutes, on average, each day – and received pedometers to track steps, aiming for 10,000 per day.
TAKEAWAY:
- Over 5 years of follow-up, the rate of breast cancer recurrence did not differ between women in the diet intervention group and those in the control group. Overall, 95 of 769 women in the intervention group and 98 of 773 in the control group had a breast cancer recurrence (hazard ratio, 0.99).
- When evaluating outcomes in the entire cohort, looking at everyone’s level of compliance with dietary recommendations, women who adhered the most to the dietary guidelines had a 41% lower recurrence risk compared with women who adhered the least (HR, 0.59).
- The greatest protective effect among women who demonstrated high compliance occurred in those with ER-positive cancers (HR, 0.42) and those with ER-positive cancers who received tamoxifen (HR, 0.30).
IN PRACTICE:
This intervention trial “did not confirm the hypothesis that a comprehensive dietary modification reduces breast cancer recurrence and metastases,” but when looking at compliance to the Mediterranean diet overall, the analysis did find “a significantly better prognosis” for women with the best adherence.
SOURCE:
The study, with first author Franco Berrino, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, was published online in Clinical Cancer Research.
LIMITATIONS:
The study relied on self-reported dietary data. No dietary instrument was used to estimate nutrient intake and the dietary index developed for the trial remains unvalidated.
DISCLOSURES:
The study was supported by the Italian Department of Health, the Associazione Italiana per la Ricerca sul Cancro, and the Vita e Salute Foundation. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
However, women at high risk for recurrence who made the greatest improvements in their diet quality demonstrated a 41% lower risk for recurrence, compared with peers who made the fewest improvements.
METHODOLOGY:
- A growing body of evidence suggests that a better dietary quality may improve survival among patients with breast cancer, but whether diet impacts breast cancer–specific mortality remains controversial.
- To better understand the relationship between diet and breast cancer outcomes, investigators recruited 1,542 women with breast cancer who had undergone surgical resection in the past 5 years and were considered high risk for recurrence.
- All women received general recommendations for cancer prevention, while the intervention group received active support to adhere to a macro–Mediterranean-style diet, which encourages mainly consuming whole grains, legumes, and high-fiber vegetables and discourages eating foods high in saturated and trans fats, processed meats, and foods and beverages high in sugar.
- Diet was assessed at baseline, 1 year, and every few months in subsequent years via food frequency diaries. Compliance with dietary recommendations for the whole cohort was assessed using a dietary index developed for the trial.
- In addition to diet, women in the diet intervention group were encouraged to maintain moderate to intense physical activity – 30 minutes, on average, each day – and received pedometers to track steps, aiming for 10,000 per day.
TAKEAWAY:
- Over 5 years of follow-up, the rate of breast cancer recurrence did not differ between women in the diet intervention group and those in the control group. Overall, 95 of 769 women in the intervention group and 98 of 773 in the control group had a breast cancer recurrence (hazard ratio, 0.99).
- When evaluating outcomes in the entire cohort, looking at everyone’s level of compliance with dietary recommendations, women who adhered the most to the dietary guidelines had a 41% lower recurrence risk compared with women who adhered the least (HR, 0.59).
- The greatest protective effect among women who demonstrated high compliance occurred in those with ER-positive cancers (HR, 0.42) and those with ER-positive cancers who received tamoxifen (HR, 0.30).
IN PRACTICE:
This intervention trial “did not confirm the hypothesis that a comprehensive dietary modification reduces breast cancer recurrence and metastases,” but when looking at compliance to the Mediterranean diet overall, the analysis did find “a significantly better prognosis” for women with the best adherence.
SOURCE:
The study, with first author Franco Berrino, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, was published online in Clinical Cancer Research.
LIMITATIONS:
The study relied on self-reported dietary data. No dietary instrument was used to estimate nutrient intake and the dietary index developed for the trial remains unvalidated.
DISCLOSURES:
The study was supported by the Italian Department of Health, the Associazione Italiana per la Ricerca sul Cancro, and the Vita e Salute Foundation. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Study confirms small blood cancer risk from CT scans
The findings, published online in Nature Medicine, are based on more than 1.3 million CT scans in nearly 900,000 people younger than 22 years old when scanned.
This study makes a “significant contribution to the understanding of the effects of ionizing radiation, specifically x-rays, on the human body at the levels of radiation exposure encountered in diagnostic CT procedures,” Peter Marsden, PhD, and Jim Thurston, radiation protection experts at Dorset County (England) Hospital, NHS Foundation Trust, said in a press release from the U.K. nonprofit Science Media Centre.
These findings highlight levels of risk that “align with those currently estimated and do not suggest that the use of CT carries a greater risk than previously thought,” Dr. Marsden and Thurston said.
Exposure to moderate- (≥ 100 mGy) to high-dose (≥ 1 Gy) ionizing radiation is a well-established risk factor for leukemia in both children and adults. However, the risk associated with low-dose exposure (< 100 mGy) typically associated with diagnostic CT exams in children and teens remains unclear.
The current study, coordinated by the International Agency for Research on Cancer, aimed to improve direct estimates of cancer risk from low-dose radiation exposure from CT scans performed in childhood and adolescence. The researchers estimated radiation doses to the active bone marrow based on body part scanned, patient characteristics, time period, and inferred CT technical parameters.
A total of 790 hematologic malignancies, including lymphoid and myeloid malignancies, were identified during follow-up. More than half (51%) of the cases were diagnosed in people under age 20 and 88.5% were diagnosed in people under age 30 years.
Overall, the observational study found a nearly twofold excess risk of all hematologic malignancies per 100 mGy in children, adolescents, and young adults, with similar risk estimates observed for lymphoid and myeloid cancers. The excess relative risk for hematologic malignancies increased as the number of CT exams increased – with risk rising by 43% per exam.
The results of this study “strengthen the findings from previous low-dose studies of a consistent and robust dose-related increased risk of radiation-induced hematological malignancies” and highlight the importance of optimizing doses in this patient population, study author Elisabeth Cardis, PhD, with the Barcelona Institute for Global Health, and colleagues concluded.
Sarah McQuaid, PhD, chair of the nuclear medicine special interest group, Institute of Physics and Engineering in Medicine, York, England, agreed.
“This publication indicates that there could be a small cancer risk from CT scans in young people, but it is important for this to be viewed in the context of the substantial benefit these scans bring, due to the important diagnostic information they provide,” Dr. McQuaid said in the press release. Overall, “the number of patients whose medical care will have been improved from these CT scans will have been very high, and lives undoubtedly saved as a result.”
The study had no commercial funding. The authors and outside experts reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The findings, published online in Nature Medicine, are based on more than 1.3 million CT scans in nearly 900,000 people younger than 22 years old when scanned.
This study makes a “significant contribution to the understanding of the effects of ionizing radiation, specifically x-rays, on the human body at the levels of radiation exposure encountered in diagnostic CT procedures,” Peter Marsden, PhD, and Jim Thurston, radiation protection experts at Dorset County (England) Hospital, NHS Foundation Trust, said in a press release from the U.K. nonprofit Science Media Centre.
These findings highlight levels of risk that “align with those currently estimated and do not suggest that the use of CT carries a greater risk than previously thought,” Dr. Marsden and Thurston said.
Exposure to moderate- (≥ 100 mGy) to high-dose (≥ 1 Gy) ionizing radiation is a well-established risk factor for leukemia in both children and adults. However, the risk associated with low-dose exposure (< 100 mGy) typically associated with diagnostic CT exams in children and teens remains unclear.
The current study, coordinated by the International Agency for Research on Cancer, aimed to improve direct estimates of cancer risk from low-dose radiation exposure from CT scans performed in childhood and adolescence. The researchers estimated radiation doses to the active bone marrow based on body part scanned, patient characteristics, time period, and inferred CT technical parameters.
A total of 790 hematologic malignancies, including lymphoid and myeloid malignancies, were identified during follow-up. More than half (51%) of the cases were diagnosed in people under age 20 and 88.5% were diagnosed in people under age 30 years.
Overall, the observational study found a nearly twofold excess risk of all hematologic malignancies per 100 mGy in children, adolescents, and young adults, with similar risk estimates observed for lymphoid and myeloid cancers. The excess relative risk for hematologic malignancies increased as the number of CT exams increased – with risk rising by 43% per exam.
The results of this study “strengthen the findings from previous low-dose studies of a consistent and robust dose-related increased risk of radiation-induced hematological malignancies” and highlight the importance of optimizing doses in this patient population, study author Elisabeth Cardis, PhD, with the Barcelona Institute for Global Health, and colleagues concluded.
Sarah McQuaid, PhD, chair of the nuclear medicine special interest group, Institute of Physics and Engineering in Medicine, York, England, agreed.
“This publication indicates that there could be a small cancer risk from CT scans in young people, but it is important for this to be viewed in the context of the substantial benefit these scans bring, due to the important diagnostic information they provide,” Dr. McQuaid said in the press release. Overall, “the number of patients whose medical care will have been improved from these CT scans will have been very high, and lives undoubtedly saved as a result.”
The study had no commercial funding. The authors and outside experts reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The findings, published online in Nature Medicine, are based on more than 1.3 million CT scans in nearly 900,000 people younger than 22 years old when scanned.
This study makes a “significant contribution to the understanding of the effects of ionizing radiation, specifically x-rays, on the human body at the levels of radiation exposure encountered in diagnostic CT procedures,” Peter Marsden, PhD, and Jim Thurston, radiation protection experts at Dorset County (England) Hospital, NHS Foundation Trust, said in a press release from the U.K. nonprofit Science Media Centre.
These findings highlight levels of risk that “align with those currently estimated and do not suggest that the use of CT carries a greater risk than previously thought,” Dr. Marsden and Thurston said.
Exposure to moderate- (≥ 100 mGy) to high-dose (≥ 1 Gy) ionizing radiation is a well-established risk factor for leukemia in both children and adults. However, the risk associated with low-dose exposure (< 100 mGy) typically associated with diagnostic CT exams in children and teens remains unclear.
The current study, coordinated by the International Agency for Research on Cancer, aimed to improve direct estimates of cancer risk from low-dose radiation exposure from CT scans performed in childhood and adolescence. The researchers estimated radiation doses to the active bone marrow based on body part scanned, patient characteristics, time period, and inferred CT technical parameters.
A total of 790 hematologic malignancies, including lymphoid and myeloid malignancies, were identified during follow-up. More than half (51%) of the cases were diagnosed in people under age 20 and 88.5% were diagnosed in people under age 30 years.
Overall, the observational study found a nearly twofold excess risk of all hematologic malignancies per 100 mGy in children, adolescents, and young adults, with similar risk estimates observed for lymphoid and myeloid cancers. The excess relative risk for hematologic malignancies increased as the number of CT exams increased – with risk rising by 43% per exam.
The results of this study “strengthen the findings from previous low-dose studies of a consistent and robust dose-related increased risk of radiation-induced hematological malignancies” and highlight the importance of optimizing doses in this patient population, study author Elisabeth Cardis, PhD, with the Barcelona Institute for Global Health, and colleagues concluded.
Sarah McQuaid, PhD, chair of the nuclear medicine special interest group, Institute of Physics and Engineering in Medicine, York, England, agreed.
“This publication indicates that there could be a small cancer risk from CT scans in young people, but it is important for this to be viewed in the context of the substantial benefit these scans bring, due to the important diagnostic information they provide,” Dr. McQuaid said in the press release. Overall, “the number of patients whose medical care will have been improved from these CT scans will have been very high, and lives undoubtedly saved as a result.”
The study had no commercial funding. The authors and outside experts reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NATURE MEDICINE
Most effective meds for alcohol use disorder flagged
TOPLINE:
In conjunction with psychosocial interventions, oral naltrexone and acamprosate are both effective first-line drug therapies for alcohol use disorder (AUD), results of a systematic review and meta-analysis found.
METHODOLOGY:
- Researchers evaluated efficacy and comparative efficacy of three therapies for AUD that are approved in the United States (acamprosate, naltrexone, and disulfiram) and six that are commonly used off-label (baclofen, gabapentin, varenicline, topiramate, prazosin, and ondansetron).
- Data came from 118 randomized clinical trials lasting at least 12 weeks with 20,976 participants.
- 74% of these studies included psychosocial co-interventions, and the primary outcome was alcohol consumption.
- Numbers needed to treat (NNT) were calculated for medications with at least moderate strength of evidence for benefit.
TAKEAWAY:
- Acamprosate (NNT = 11) and naltrexone (50 mg/day; NNT = 18) had the highest strength of evidence and were both associated with statistically significant improvement in drinking outcomes.
- Oral naltrexone but not acamprosate was also associated with lower rates of return to heavy drinking (NNT = 11), compared with placebo.
- Injectable naltrexone was not associated with return to any or heavy drinking but was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, –4.99 days).
- The four trials that directly compared acamprosate with oral naltrexone did not consistently establish superiority of either medication for alcohol use outcomes, and among off-label drugs, only topiramate had moderate strength of evidence for benefit.
IN PRACTICE:
“Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. In conjunction with psychosocial interventions, these findings support the use of oral naltrexone, 50 mg/day, and acamprosate as first-line pharmacotherapies for alcohol use disorder,” the authors write.
SOURCE:
The study, with first author Melissa McPheeters, PhD, MPH, RTI International, Research Triangle Park, North Carolina, was published online in JAMA.
LIMITATIONS:
Most study participants had moderate to severe AUD, and the applicability of the findings to people with mild AUD is uncertain. The mean age of participants was typically between ages 40 and 49 years, and it’s unclear whether the medications have similar efficacy for older or younger age groups. Information on adverse effects was limited.
DISCLOSURES:
Funding for the study was provided by the Agency for Healthcare Research and Quality of the U.S. Department of Health & Human Services. The authors have disclosed no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
In conjunction with psychosocial interventions, oral naltrexone and acamprosate are both effective first-line drug therapies for alcohol use disorder (AUD), results of a systematic review and meta-analysis found.
METHODOLOGY:
- Researchers evaluated efficacy and comparative efficacy of three therapies for AUD that are approved in the United States (acamprosate, naltrexone, and disulfiram) and six that are commonly used off-label (baclofen, gabapentin, varenicline, topiramate, prazosin, and ondansetron).
- Data came from 118 randomized clinical trials lasting at least 12 weeks with 20,976 participants.
- 74% of these studies included psychosocial co-interventions, and the primary outcome was alcohol consumption.
- Numbers needed to treat (NNT) were calculated for medications with at least moderate strength of evidence for benefit.
TAKEAWAY:
- Acamprosate (NNT = 11) and naltrexone (50 mg/day; NNT = 18) had the highest strength of evidence and were both associated with statistically significant improvement in drinking outcomes.
- Oral naltrexone but not acamprosate was also associated with lower rates of return to heavy drinking (NNT = 11), compared with placebo.
- Injectable naltrexone was not associated with return to any or heavy drinking but was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, –4.99 days).
- The four trials that directly compared acamprosate with oral naltrexone did not consistently establish superiority of either medication for alcohol use outcomes, and among off-label drugs, only topiramate had moderate strength of evidence for benefit.
IN PRACTICE:
“Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. In conjunction with psychosocial interventions, these findings support the use of oral naltrexone, 50 mg/day, and acamprosate as first-line pharmacotherapies for alcohol use disorder,” the authors write.
SOURCE:
The study, with first author Melissa McPheeters, PhD, MPH, RTI International, Research Triangle Park, North Carolina, was published online in JAMA.
LIMITATIONS:
Most study participants had moderate to severe AUD, and the applicability of the findings to people with mild AUD is uncertain. The mean age of participants was typically between ages 40 and 49 years, and it’s unclear whether the medications have similar efficacy for older or younger age groups. Information on adverse effects was limited.
DISCLOSURES:
Funding for the study was provided by the Agency for Healthcare Research and Quality of the U.S. Department of Health & Human Services. The authors have disclosed no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
In conjunction with psychosocial interventions, oral naltrexone and acamprosate are both effective first-line drug therapies for alcohol use disorder (AUD), results of a systematic review and meta-analysis found.
METHODOLOGY:
- Researchers evaluated efficacy and comparative efficacy of three therapies for AUD that are approved in the United States (acamprosate, naltrexone, and disulfiram) and six that are commonly used off-label (baclofen, gabapentin, varenicline, topiramate, prazosin, and ondansetron).
- Data came from 118 randomized clinical trials lasting at least 12 weeks with 20,976 participants.
- 74% of these studies included psychosocial co-interventions, and the primary outcome was alcohol consumption.
- Numbers needed to treat (NNT) were calculated for medications with at least moderate strength of evidence for benefit.
TAKEAWAY:
- Acamprosate (NNT = 11) and naltrexone (50 mg/day; NNT = 18) had the highest strength of evidence and were both associated with statistically significant improvement in drinking outcomes.
- Oral naltrexone but not acamprosate was also associated with lower rates of return to heavy drinking (NNT = 11), compared with placebo.
- Injectable naltrexone was not associated with return to any or heavy drinking but was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, –4.99 days).
- The four trials that directly compared acamprosate with oral naltrexone did not consistently establish superiority of either medication for alcohol use outcomes, and among off-label drugs, only topiramate had moderate strength of evidence for benefit.
IN PRACTICE:
“Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. In conjunction with psychosocial interventions, these findings support the use of oral naltrexone, 50 mg/day, and acamprosate as first-line pharmacotherapies for alcohol use disorder,” the authors write.
SOURCE:
The study, with first author Melissa McPheeters, PhD, MPH, RTI International, Research Triangle Park, North Carolina, was published online in JAMA.
LIMITATIONS:
Most study participants had moderate to severe AUD, and the applicability of the findings to people with mild AUD is uncertain. The mean age of participants was typically between ages 40 and 49 years, and it’s unclear whether the medications have similar efficacy for older or younger age groups. Information on adverse effects was limited.
DISCLOSURES:
Funding for the study was provided by the Agency for Healthcare Research and Quality of the U.S. Department of Health & Human Services. The authors have disclosed no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
Atrial fibrillation linked to dementia, especially when diagnosed before age 65 years
TOPLINE:
Adults with atrial fibrillation (AFib) are at increased risk for dementia, especially when AFib occurs before age 65 years, new research shows. Investigators note the findings highlight the importance of monitoring cognitive function in adults with AF.
METHODOLOGY:
- This prospective, population-based cohort study leveraged data from 433,746 UK Biobank participants (55% women), including 30,601 with AFib, who were followed for a median of 12.6 years
- Incident cases of dementia were determined through linkage from multiple databases.
- Cox proportional hazards models and propensity score matching were used to estimate the association between age at onset of AFib and incident dementia.
TAKEAWAY:
- During follow-up, new-onset dementia occurred in 5,898 participants (2,546 with Alzheimer’s disease [AD] and 1,211 with vascular dementia [VD]), of which, 1,031 had AFib (350 with AD; 320 with VD).
- Compared with participants without AFib, those with AFib had a 42% higher risk for all-cause dementia (adjusted hazard ratio, 1.42; P < .001) and more than double the risk for VD (aHR, 2.06; P < .001), but no significantly higher risk for AD.
- Younger age at AFib onset was associated with higher risks for all-cause dementia, AD and VD, with aHRs per 10-year decrease of 1.23, 1.27, and 1.35, respectively (P < .001 for all).
- After propensity score matching, AFib onset before age 65 years had the highest risk for all-cause dementia (aHR, 1.82; P < .001), followed by AF onset at age 65-74 years (aHR, 1.47; P < .001). Similar results were seen in AD and VD.
IN PRACTICE:
“The findings indicate that careful monitoring of cognitive function for patients with a younger [AFib] onset age, particularly those diagnosed with [AFib] before age 65 years, is important to attenuate the risk of subsequent dementia,” the authors write.
SOURCE:
The study, with first author Wenya Zhang, with the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, was published online in JAMA Network Open.
LIMITATIONS:
Because the study was observational, a cause-effect relationship cannot be established. Despite the adjustment for many underlying confounders, residual unidentified confounders may still exist. The vast majority of participants were White. The analyses did not consider the potential impact of effective treatment of AFib on dementia risk.
DISCLOSURES:
The study had no commercial funding. The authors have declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Adults with atrial fibrillation (AFib) are at increased risk for dementia, especially when AFib occurs before age 65 years, new research shows. Investigators note the findings highlight the importance of monitoring cognitive function in adults with AF.
METHODOLOGY:
- This prospective, population-based cohort study leveraged data from 433,746 UK Biobank participants (55% women), including 30,601 with AFib, who were followed for a median of 12.6 years
- Incident cases of dementia were determined through linkage from multiple databases.
- Cox proportional hazards models and propensity score matching were used to estimate the association between age at onset of AFib and incident dementia.
TAKEAWAY:
- During follow-up, new-onset dementia occurred in 5,898 participants (2,546 with Alzheimer’s disease [AD] and 1,211 with vascular dementia [VD]), of which, 1,031 had AFib (350 with AD; 320 with VD).
- Compared with participants without AFib, those with AFib had a 42% higher risk for all-cause dementia (adjusted hazard ratio, 1.42; P < .001) and more than double the risk for VD (aHR, 2.06; P < .001), but no significantly higher risk for AD.
- Younger age at AFib onset was associated with higher risks for all-cause dementia, AD and VD, with aHRs per 10-year decrease of 1.23, 1.27, and 1.35, respectively (P < .001 for all).
- After propensity score matching, AFib onset before age 65 years had the highest risk for all-cause dementia (aHR, 1.82; P < .001), followed by AF onset at age 65-74 years (aHR, 1.47; P < .001). Similar results were seen in AD and VD.
IN PRACTICE:
“The findings indicate that careful monitoring of cognitive function for patients with a younger [AFib] onset age, particularly those diagnosed with [AFib] before age 65 years, is important to attenuate the risk of subsequent dementia,” the authors write.
SOURCE:
The study, with first author Wenya Zhang, with the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, was published online in JAMA Network Open.
LIMITATIONS:
Because the study was observational, a cause-effect relationship cannot be established. Despite the adjustment for many underlying confounders, residual unidentified confounders may still exist. The vast majority of participants were White. The analyses did not consider the potential impact of effective treatment of AFib on dementia risk.
DISCLOSURES:
The study had no commercial funding. The authors have declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Adults with atrial fibrillation (AFib) are at increased risk for dementia, especially when AFib occurs before age 65 years, new research shows. Investigators note the findings highlight the importance of monitoring cognitive function in adults with AF.
METHODOLOGY:
- This prospective, population-based cohort study leveraged data from 433,746 UK Biobank participants (55% women), including 30,601 with AFib, who were followed for a median of 12.6 years
- Incident cases of dementia were determined through linkage from multiple databases.
- Cox proportional hazards models and propensity score matching were used to estimate the association between age at onset of AFib and incident dementia.
TAKEAWAY:
- During follow-up, new-onset dementia occurred in 5,898 participants (2,546 with Alzheimer’s disease [AD] and 1,211 with vascular dementia [VD]), of which, 1,031 had AFib (350 with AD; 320 with VD).
- Compared with participants without AFib, those with AFib had a 42% higher risk for all-cause dementia (adjusted hazard ratio, 1.42; P < .001) and more than double the risk for VD (aHR, 2.06; P < .001), but no significantly higher risk for AD.
- Younger age at AFib onset was associated with higher risks for all-cause dementia, AD and VD, with aHRs per 10-year decrease of 1.23, 1.27, and 1.35, respectively (P < .001 for all).
- After propensity score matching, AFib onset before age 65 years had the highest risk for all-cause dementia (aHR, 1.82; P < .001), followed by AF onset at age 65-74 years (aHR, 1.47; P < .001). Similar results were seen in AD and VD.
IN PRACTICE:
“The findings indicate that careful monitoring of cognitive function for patients with a younger [AFib] onset age, particularly those diagnosed with [AFib] before age 65 years, is important to attenuate the risk of subsequent dementia,” the authors write.
SOURCE:
The study, with first author Wenya Zhang, with the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, was published online in JAMA Network Open.
LIMITATIONS:
Because the study was observational, a cause-effect relationship cannot be established. Despite the adjustment for many underlying confounders, residual unidentified confounders may still exist. The vast majority of participants were White. The analyses did not consider the potential impact of effective treatment of AFib on dementia risk.
DISCLOSURES:
The study had no commercial funding. The authors have declared no conflicts of interest.
A version of this article appeared on Medscape.com.
RNA therapeutics will ‘change everything’ in epilepsy
Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.
But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.
“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.
Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.
Dr. Kaye said.
Thank COVID?
Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.
Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.
Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.
RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.
Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.
“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.
“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
Hope for Dravet syndrome
Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.
Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.
The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.
“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.
Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.
“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.
“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.
“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
A promising future
Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”
And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.
Take, for example, a case reported recently in the New England Journal of Medicine.
Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.
One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.
However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”
“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.
The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.
A version of this article first appeared on Medscape.com.
Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.
But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.
“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.
Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.
Dr. Kaye said.
Thank COVID?
Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.
Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.
Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.
RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.
Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.
“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.
“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
Hope for Dravet syndrome
Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.
Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.
The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.
“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.
Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.
“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.
“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.
“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
A promising future
Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”
And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.
Take, for example, a case reported recently in the New England Journal of Medicine.
Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.
One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.
However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”
“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.
The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.
A version of this article first appeared on Medscape.com.
Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.
But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.
“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.
Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.
Dr. Kaye said.
Thank COVID?
Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.
Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.
Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.
RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.
Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.
“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.
“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
Hope for Dravet syndrome
Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.
Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.
The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.
“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.
Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.
“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.
“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.
“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
A promising future
Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”
And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.
Take, for example, a case reported recently in the New England Journal of Medicine.
Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.
One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.
However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”
“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.
The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.
A version of this article first appeared on Medscape.com.
Pervasive ‘forever chemicals’ linked to thyroid cancer?
The study suggests that higher exposure to per- and polyfluoroalkyl substances (PFAS), specifically perfluorooctanesulfonic acid (n-PFOS), may increase a person’s risk for thyroid cancer by 56%.
Several news outlets played up the findings, published online in eBioMedicine. “Dangerous ‘Forever Chemicals’ in Your Everyday Items Are Causing Cancer,” Newsweek reported.
But Gideon Meyerowitz-Katz, PhD, an epidemiologist at the University of Wollongong (Australia), voiced his skepticism.
“While it’s possible that PFAS might be causing thyroid cancer, the evidence thus far is unconvincing and probably not worth worrying about,” said Dr. Meyerowitz-Katz, who was not involved in the research.
PFAS and thyroid cancer
PFAS are a class of widely used synthetic chemicals found in many consumer and industrial products, including nonstick cookware, stain-repellent carpets, waterproof rain gear, microwave popcorn bags, and firefighting foam.
These substances have been dubbed “forever chemicals” because they do not degrade and are ubiquitous in the environment.
Exposure to endocrine-disrupting chemicals, including PFAS, has been identified as a potential risk factor for thyroid cancer, with some research linking PFAS exposure to thyroid dysfunction and carcinogenesis.
To investigate further, the researchers performed a nested case-control study of 86 patients with thyroid cancer using plasma samples collected at or before diagnosis and 86 controls without cancer who were matched on age, sex, race/ethnicity, body weight, smoking status, and year of sample collection.
Eighteen individual PFAS were measured in plasma samples; 10 were undetectable and were therefore excluded from the analysis. Of the remaining eight PFAS, only one showed a statistically significant correlation with thyroid cancer.
Specifically, the researchers found that exposure to n-PFOS was associated with a 56% increased risk for thyroid cancer among people who had a high level of the chemical in their blood (adjusted odds ratio, 1.56; P = .004). The results were similar when patients with papillary thyroid cancer only were included (aOR, 1.56; P = .009).
A separate longitudinal analysis of 31 patients diagnosed with thyroid cancer 1 year or more after plasma sample collection and 31 controls confirmed the positive association between n-PFOS and thyroid cancer (aOR, 2.67; P < .001). The longitudinal analysis also suggested correlations for a few other PFAS.
“This study supports the hypothesis that PFAS exposure may be associated with increased risk of thyroid cancer,” the authors concluded.
But in a Substack post, Dr. Meyerowitz-Katz said that it’s important to put the findings into “proper context before getting terrified about this all-new cancer risk.”
First, this study was “genuinely tiny,” with data on just 88 people with thyroid cancer and 88 controls, a limitation the researchers also acknowledged.
“That’s really not enough to do any sort of robust epidemiological analysis – you can generate interesting correlations, but what those correlations mean is anyone’s guess,” Dr. Meyerowitz-Katz said.
Even more importantly, one could easily argue that the results of this study show that most PFAS aren’t associated with thyroid cancer, given that there was no strong association for seven of the eight PFAS measured, he explained.
“There are no serious methodological concerns here, but equally there’s just not much you can reasonably gather from finding a single correlation among a vast ocean of possibilities,” Dr. Meyerowitz-Katz wrote. “Maybe there’s a correlation there, but you’d need to investigate this in much bigger samples, with more controls, and better data, to understand what that correlation means.”
Bottom line, Dr. Meyerowitz-Katz explained, is that “the link between PFAS and thyroid cancer is, at best, incredibly weak.”
Funding for the study was provided by the National Institutes of Health and The Andrea and Charles Bronfman Philanthropies. One coauthor is cofounder of Linus Biotechnology and is owner of a license agreement with NIES (Japan); received honoraria and travel compensation for lectures for the Bio-Echo and Brin foundations; and has 22 patents at various stages. Dr. Meyerowitz-Katz has no relevant disclosures.
A version of this article appeared on Medscape.com.
The study suggests that higher exposure to per- and polyfluoroalkyl substances (PFAS), specifically perfluorooctanesulfonic acid (n-PFOS), may increase a person’s risk for thyroid cancer by 56%.
Several news outlets played up the findings, published online in eBioMedicine. “Dangerous ‘Forever Chemicals’ in Your Everyday Items Are Causing Cancer,” Newsweek reported.
But Gideon Meyerowitz-Katz, PhD, an epidemiologist at the University of Wollongong (Australia), voiced his skepticism.
“While it’s possible that PFAS might be causing thyroid cancer, the evidence thus far is unconvincing and probably not worth worrying about,” said Dr. Meyerowitz-Katz, who was not involved in the research.
PFAS and thyroid cancer
PFAS are a class of widely used synthetic chemicals found in many consumer and industrial products, including nonstick cookware, stain-repellent carpets, waterproof rain gear, microwave popcorn bags, and firefighting foam.
These substances have been dubbed “forever chemicals” because they do not degrade and are ubiquitous in the environment.
Exposure to endocrine-disrupting chemicals, including PFAS, has been identified as a potential risk factor for thyroid cancer, with some research linking PFAS exposure to thyroid dysfunction and carcinogenesis.
To investigate further, the researchers performed a nested case-control study of 86 patients with thyroid cancer using plasma samples collected at or before diagnosis and 86 controls without cancer who were matched on age, sex, race/ethnicity, body weight, smoking status, and year of sample collection.
Eighteen individual PFAS were measured in plasma samples; 10 were undetectable and were therefore excluded from the analysis. Of the remaining eight PFAS, only one showed a statistically significant correlation with thyroid cancer.
Specifically, the researchers found that exposure to n-PFOS was associated with a 56% increased risk for thyroid cancer among people who had a high level of the chemical in their blood (adjusted odds ratio, 1.56; P = .004). The results were similar when patients with papillary thyroid cancer only were included (aOR, 1.56; P = .009).
A separate longitudinal analysis of 31 patients diagnosed with thyroid cancer 1 year or more after plasma sample collection and 31 controls confirmed the positive association between n-PFOS and thyroid cancer (aOR, 2.67; P < .001). The longitudinal analysis also suggested correlations for a few other PFAS.
“This study supports the hypothesis that PFAS exposure may be associated with increased risk of thyroid cancer,” the authors concluded.
But in a Substack post, Dr. Meyerowitz-Katz said that it’s important to put the findings into “proper context before getting terrified about this all-new cancer risk.”
First, this study was “genuinely tiny,” with data on just 88 people with thyroid cancer and 88 controls, a limitation the researchers also acknowledged.
“That’s really not enough to do any sort of robust epidemiological analysis – you can generate interesting correlations, but what those correlations mean is anyone’s guess,” Dr. Meyerowitz-Katz said.
Even more importantly, one could easily argue that the results of this study show that most PFAS aren’t associated with thyroid cancer, given that there was no strong association for seven of the eight PFAS measured, he explained.
“There are no serious methodological concerns here, but equally there’s just not much you can reasonably gather from finding a single correlation among a vast ocean of possibilities,” Dr. Meyerowitz-Katz wrote. “Maybe there’s a correlation there, but you’d need to investigate this in much bigger samples, with more controls, and better data, to understand what that correlation means.”
Bottom line, Dr. Meyerowitz-Katz explained, is that “the link between PFAS and thyroid cancer is, at best, incredibly weak.”
Funding for the study was provided by the National Institutes of Health and The Andrea and Charles Bronfman Philanthropies. One coauthor is cofounder of Linus Biotechnology and is owner of a license agreement with NIES (Japan); received honoraria and travel compensation for lectures for the Bio-Echo and Brin foundations; and has 22 patents at various stages. Dr. Meyerowitz-Katz has no relevant disclosures.
A version of this article appeared on Medscape.com.
The study suggests that higher exposure to per- and polyfluoroalkyl substances (PFAS), specifically perfluorooctanesulfonic acid (n-PFOS), may increase a person’s risk for thyroid cancer by 56%.
Several news outlets played up the findings, published online in eBioMedicine. “Dangerous ‘Forever Chemicals’ in Your Everyday Items Are Causing Cancer,” Newsweek reported.
But Gideon Meyerowitz-Katz, PhD, an epidemiologist at the University of Wollongong (Australia), voiced his skepticism.
“While it’s possible that PFAS might be causing thyroid cancer, the evidence thus far is unconvincing and probably not worth worrying about,” said Dr. Meyerowitz-Katz, who was not involved in the research.
PFAS and thyroid cancer
PFAS are a class of widely used synthetic chemicals found in many consumer and industrial products, including nonstick cookware, stain-repellent carpets, waterproof rain gear, microwave popcorn bags, and firefighting foam.
These substances have been dubbed “forever chemicals” because they do not degrade and are ubiquitous in the environment.
Exposure to endocrine-disrupting chemicals, including PFAS, has been identified as a potential risk factor for thyroid cancer, with some research linking PFAS exposure to thyroid dysfunction and carcinogenesis.
To investigate further, the researchers performed a nested case-control study of 86 patients with thyroid cancer using plasma samples collected at or before diagnosis and 86 controls without cancer who were matched on age, sex, race/ethnicity, body weight, smoking status, and year of sample collection.
Eighteen individual PFAS were measured in plasma samples; 10 were undetectable and were therefore excluded from the analysis. Of the remaining eight PFAS, only one showed a statistically significant correlation with thyroid cancer.
Specifically, the researchers found that exposure to n-PFOS was associated with a 56% increased risk for thyroid cancer among people who had a high level of the chemical in their blood (adjusted odds ratio, 1.56; P = .004). The results were similar when patients with papillary thyroid cancer only were included (aOR, 1.56; P = .009).
A separate longitudinal analysis of 31 patients diagnosed with thyroid cancer 1 year or more after plasma sample collection and 31 controls confirmed the positive association between n-PFOS and thyroid cancer (aOR, 2.67; P < .001). The longitudinal analysis also suggested correlations for a few other PFAS.
“This study supports the hypothesis that PFAS exposure may be associated with increased risk of thyroid cancer,” the authors concluded.
But in a Substack post, Dr. Meyerowitz-Katz said that it’s important to put the findings into “proper context before getting terrified about this all-new cancer risk.”
First, this study was “genuinely tiny,” with data on just 88 people with thyroid cancer and 88 controls, a limitation the researchers also acknowledged.
“That’s really not enough to do any sort of robust epidemiological analysis – you can generate interesting correlations, but what those correlations mean is anyone’s guess,” Dr. Meyerowitz-Katz said.
Even more importantly, one could easily argue that the results of this study show that most PFAS aren’t associated with thyroid cancer, given that there was no strong association for seven of the eight PFAS measured, he explained.
“There are no serious methodological concerns here, but equally there’s just not much you can reasonably gather from finding a single correlation among a vast ocean of possibilities,” Dr. Meyerowitz-Katz wrote. “Maybe there’s a correlation there, but you’d need to investigate this in much bigger samples, with more controls, and better data, to understand what that correlation means.”
Bottom line, Dr. Meyerowitz-Katz explained, is that “the link between PFAS and thyroid cancer is, at best, incredibly weak.”
Funding for the study was provided by the National Institutes of Health and The Andrea and Charles Bronfman Philanthropies. One coauthor is cofounder of Linus Biotechnology and is owner of a license agreement with NIES (Japan); received honoraria and travel compensation for lectures for the Bio-Echo and Brin foundations; and has 22 patents at various stages. Dr. Meyerowitz-Katz has no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM EBIOMEDICINE
Enhanced natural killer cell therapy shows promise in Alzheimer’s
BOSTON – .
SNK01, being developed by NKGen Biotech, is an autologous, nongenetically modified NK cell product that has enhanced cytotoxicity and activating receptor expression.
“When we give these enhanced natural killer cells intravenously, not only do they get into the brain, but we’ve shown, through CSF biomarker data, that they reduce both amyloid and tau proteins, dramatically reducing the neuroinflammation,” said Paul Song, MD, chief executive officer of NKGen Biotech.
“Remarkably,” in the first 6 months, 90% of patients with Alzheimer’s disease demonstrated improvement or maintained stable cognitive function, based on the Alzheimer’s Disease Composite Score (ADCOMS), suggesting that SNK01 may do more than simply slow disease progression, Dr. Song said.
The findings were presented at the 16th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
Sound rationale
NK cells are an essential part of the innate immune system that can shape the adaptive response by eliminating activated (not resting) autologous CD4+ T cells. Weak or deficient NK cells have been found to correlate with various diseases, including autoimmune diseases, and emerging data suggest an autoimmune component to Alzheimer’s disease.
The phase 1 study evaluated the safety, tolerability, and exploratory efficacy of SNK01 given intravenously in escalating doses every 3 weeks (four treatments in total).
Participants included 10 patients with Alzheimer’s disease confirmed by imaging. Five had mild Alzheimer’s disease, three had moderate Alzheimer’s disease, and two had advanced Alzheimer’s disease, based on baseline Clinical Dementia Rating–Sum of Boxes (CDR-SB) scores. Median baseline CDR-SB score was 9 (range, 4-18).
Cognitive assessments included CDR-SB, Mini-Mental State Examination (MMSE), Alzheimer’s disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and ADCOMS. CSF biomarker analyses were performed at baseline and at 1 and 12 weeks after the final dose (weeks 11 and 22, respectively).
NK cells were successfully activated and expanded in all 10 patients and no treatment-related adverse events were observed.
Based on the CSF biomarker data, SNK01 crossed the blood–brain barrier and reduced CSF amyloid-beta 42/40 and pTau181 levels and neuroinflammation, as measured by glial fibrillary acid protein (GFAP), and the effects appeared to persist 12 weeks after the final dose.
The exploratory efficacy data show that, 1 week after final dose (week 11), compared with baseline, 30% of patients showed clinical improvement on the composite ADCOMS and 60% had a stable ADCOMS score; 50%-70% of patients were stable or improved on the CDR-SB, ADAS-Cog and/or MMSE.
“One patient went from a MMSE score of 14, which is moderate dementia, to 22, which is mild cognitive impairment,” said Dr. Song.
At 12 weeks after the final dose (week 22), 44%-89% of patients remained stable or improved in all cognitive scores compared with week 11; and 50% of the patients with stable ADCOMS scores at week 11 remained stable.
Based on the positive phase 1 data, the Food and Drug Administration has approved a phase 1/2a study in patients with moderate Alzheimer’s disease. “The trial will use a much higher dose and a prolonged dosing regimen and we think we’ll see even more dramatic results with more sustained higher dosing,” Dr. Song said.
Down the road, it will be interesting to see how NK cell therapy could “complement” anti-amyloid and anti-tau therapies, he added.
Ideal treatment approach
Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said NK cells have “natural abilities that could make them an ideal treatment approach for Alzheimer’s and similar neurodegenerative diseases.
“NK cells have properties that allow them to recognize and destroy diseased brain cells while leaving healthy cells intact, without causing excessive inflammation or autoimmune issues. It has historically been difficult to get immune cells to access the privileged immunological environment of the brain,” Dr. Lakhan explained.
“However, this line of early research shows that NK cells safely crosses the blood–brain barrier, infiltrates brain tissue, and may stave off Alzheimer’s disease as measured by biomarkers and clinical symptoms,” he noted.
“This emerging cell-based immunotherapy is highly-specific to the cells responsible for Alzheimer’s, avoids drug resistance, has long-lasting results, and has fewer side effects than drug counterparts,” Dr. Lakhan said.
The trial was sponsored by NKGen Biotech. Dr. Song and six coauthors are employees and shareholders in the company. Dr. Lakhan reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
BOSTON – .
SNK01, being developed by NKGen Biotech, is an autologous, nongenetically modified NK cell product that has enhanced cytotoxicity and activating receptor expression.
“When we give these enhanced natural killer cells intravenously, not only do they get into the brain, but we’ve shown, through CSF biomarker data, that they reduce both amyloid and tau proteins, dramatically reducing the neuroinflammation,” said Paul Song, MD, chief executive officer of NKGen Biotech.
“Remarkably,” in the first 6 months, 90% of patients with Alzheimer’s disease demonstrated improvement or maintained stable cognitive function, based on the Alzheimer’s Disease Composite Score (ADCOMS), suggesting that SNK01 may do more than simply slow disease progression, Dr. Song said.
The findings were presented at the 16th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
Sound rationale
NK cells are an essential part of the innate immune system that can shape the adaptive response by eliminating activated (not resting) autologous CD4+ T cells. Weak or deficient NK cells have been found to correlate with various diseases, including autoimmune diseases, and emerging data suggest an autoimmune component to Alzheimer’s disease.
The phase 1 study evaluated the safety, tolerability, and exploratory efficacy of SNK01 given intravenously in escalating doses every 3 weeks (four treatments in total).
Participants included 10 patients with Alzheimer’s disease confirmed by imaging. Five had mild Alzheimer’s disease, three had moderate Alzheimer’s disease, and two had advanced Alzheimer’s disease, based on baseline Clinical Dementia Rating–Sum of Boxes (CDR-SB) scores. Median baseline CDR-SB score was 9 (range, 4-18).
Cognitive assessments included CDR-SB, Mini-Mental State Examination (MMSE), Alzheimer’s disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and ADCOMS. CSF biomarker analyses were performed at baseline and at 1 and 12 weeks after the final dose (weeks 11 and 22, respectively).
NK cells were successfully activated and expanded in all 10 patients and no treatment-related adverse events were observed.
Based on the CSF biomarker data, SNK01 crossed the blood–brain barrier and reduced CSF amyloid-beta 42/40 and pTau181 levels and neuroinflammation, as measured by glial fibrillary acid protein (GFAP), and the effects appeared to persist 12 weeks after the final dose.
The exploratory efficacy data show that, 1 week after final dose (week 11), compared with baseline, 30% of patients showed clinical improvement on the composite ADCOMS and 60% had a stable ADCOMS score; 50%-70% of patients were stable or improved on the CDR-SB, ADAS-Cog and/or MMSE.
“One patient went from a MMSE score of 14, which is moderate dementia, to 22, which is mild cognitive impairment,” said Dr. Song.
At 12 weeks after the final dose (week 22), 44%-89% of patients remained stable or improved in all cognitive scores compared with week 11; and 50% of the patients with stable ADCOMS scores at week 11 remained stable.
Based on the positive phase 1 data, the Food and Drug Administration has approved a phase 1/2a study in patients with moderate Alzheimer’s disease. “The trial will use a much higher dose and a prolonged dosing regimen and we think we’ll see even more dramatic results with more sustained higher dosing,” Dr. Song said.
Down the road, it will be interesting to see how NK cell therapy could “complement” anti-amyloid and anti-tau therapies, he added.
Ideal treatment approach
Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said NK cells have “natural abilities that could make them an ideal treatment approach for Alzheimer’s and similar neurodegenerative diseases.
“NK cells have properties that allow them to recognize and destroy diseased brain cells while leaving healthy cells intact, without causing excessive inflammation or autoimmune issues. It has historically been difficult to get immune cells to access the privileged immunological environment of the brain,” Dr. Lakhan explained.
“However, this line of early research shows that NK cells safely crosses the blood–brain barrier, infiltrates brain tissue, and may stave off Alzheimer’s disease as measured by biomarkers and clinical symptoms,” he noted.
“This emerging cell-based immunotherapy is highly-specific to the cells responsible for Alzheimer’s, avoids drug resistance, has long-lasting results, and has fewer side effects than drug counterparts,” Dr. Lakhan said.
The trial was sponsored by NKGen Biotech. Dr. Song and six coauthors are employees and shareholders in the company. Dr. Lakhan reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
BOSTON – .
SNK01, being developed by NKGen Biotech, is an autologous, nongenetically modified NK cell product that has enhanced cytotoxicity and activating receptor expression.
“When we give these enhanced natural killer cells intravenously, not only do they get into the brain, but we’ve shown, through CSF biomarker data, that they reduce both amyloid and tau proteins, dramatically reducing the neuroinflammation,” said Paul Song, MD, chief executive officer of NKGen Biotech.
“Remarkably,” in the first 6 months, 90% of patients with Alzheimer’s disease demonstrated improvement or maintained stable cognitive function, based on the Alzheimer’s Disease Composite Score (ADCOMS), suggesting that SNK01 may do more than simply slow disease progression, Dr. Song said.
The findings were presented at the 16th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
Sound rationale
NK cells are an essential part of the innate immune system that can shape the adaptive response by eliminating activated (not resting) autologous CD4+ T cells. Weak or deficient NK cells have been found to correlate with various diseases, including autoimmune diseases, and emerging data suggest an autoimmune component to Alzheimer’s disease.
The phase 1 study evaluated the safety, tolerability, and exploratory efficacy of SNK01 given intravenously in escalating doses every 3 weeks (four treatments in total).
Participants included 10 patients with Alzheimer’s disease confirmed by imaging. Five had mild Alzheimer’s disease, three had moderate Alzheimer’s disease, and two had advanced Alzheimer’s disease, based on baseline Clinical Dementia Rating–Sum of Boxes (CDR-SB) scores. Median baseline CDR-SB score was 9 (range, 4-18).
Cognitive assessments included CDR-SB, Mini-Mental State Examination (MMSE), Alzheimer’s disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and ADCOMS. CSF biomarker analyses were performed at baseline and at 1 and 12 weeks after the final dose (weeks 11 and 22, respectively).
NK cells were successfully activated and expanded in all 10 patients and no treatment-related adverse events were observed.
Based on the CSF biomarker data, SNK01 crossed the blood–brain barrier and reduced CSF amyloid-beta 42/40 and pTau181 levels and neuroinflammation, as measured by glial fibrillary acid protein (GFAP), and the effects appeared to persist 12 weeks after the final dose.
The exploratory efficacy data show that, 1 week after final dose (week 11), compared with baseline, 30% of patients showed clinical improvement on the composite ADCOMS and 60% had a stable ADCOMS score; 50%-70% of patients were stable or improved on the CDR-SB, ADAS-Cog and/or MMSE.
“One patient went from a MMSE score of 14, which is moderate dementia, to 22, which is mild cognitive impairment,” said Dr. Song.
At 12 weeks after the final dose (week 22), 44%-89% of patients remained stable or improved in all cognitive scores compared with week 11; and 50% of the patients with stable ADCOMS scores at week 11 remained stable.
Based on the positive phase 1 data, the Food and Drug Administration has approved a phase 1/2a study in patients with moderate Alzheimer’s disease. “The trial will use a much higher dose and a prolonged dosing regimen and we think we’ll see even more dramatic results with more sustained higher dosing,” Dr. Song said.
Down the road, it will be interesting to see how NK cell therapy could “complement” anti-amyloid and anti-tau therapies, he added.
Ideal treatment approach
Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said NK cells have “natural abilities that could make them an ideal treatment approach for Alzheimer’s and similar neurodegenerative diseases.
“NK cells have properties that allow them to recognize and destroy diseased brain cells while leaving healthy cells intact, without causing excessive inflammation or autoimmune issues. It has historically been difficult to get immune cells to access the privileged immunological environment of the brain,” Dr. Lakhan explained.
“However, this line of early research shows that NK cells safely crosses the blood–brain barrier, infiltrates brain tissue, and may stave off Alzheimer’s disease as measured by biomarkers and clinical symptoms,” he noted.
“This emerging cell-based immunotherapy is highly-specific to the cells responsible for Alzheimer’s, avoids drug resistance, has long-lasting results, and has fewer side effects than drug counterparts,” Dr. Lakhan said.
The trial was sponsored by NKGen Biotech. Dr. Song and six coauthors are employees and shareholders in the company. Dr. Lakhan reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM CTAD 2023
ADC with radiotherapy for brain mets ups risk of necrosis
TOPLINE:
, a new retrospective study suggests.
METHODOLOGY:
- Stereotactic radiotherapy is a key treatment for patients with brain metastases, but some develop radiation necrosis. Because ADCs can help shrink brain metastases as well, the researchers wanted to see whether adding an ADC to stereotactic radiotherapy increased patients’ risk of symptomatic radiation necrosis.
- The study included 98 patients (84% women; median age, 55 years) with brain metastases who received at least one course of stereotactic radiotherapy for intact brain metastases and at least one dose of trastuzumab emtansine, trastuzumab deruxtecan, or sacituzumab govitecan.
- Stereotactic radiotherapy was considered concurrent with ADC therapy if delivered within 7 days before the ADC or within 21 days after the ADC. The control cohort included patients with brain metastases treated sequentially with stereotactic radiotherapy and an ADC.
- Symptomatic radiation necrosis was the primary outcome, and the researchers used competing risks regression models to analyze the impact of concurrent therapy.
TAKEAWAY:
- For the entire cohort, the 24-month cumulative incidence of symptomatic radiation necrosis was 8.5%. ADC therapy given concurrently with stereotactic radiotherapy was associated with higher risk for symptomatic radiation necrosis in univariable analysis (subdistribution hazard ratio, 4.01) and multivariable analysis (SHR, 4.31) that controlled for prior radiotherapy and volume of brain metastases.
- The risk of symptomatic radiation necrosis with concurrent ADC was modest for patients with small brain metastases who received a first course of stereotactic radiotherapy but was substantial for those with larger and reirradiated lesions treated with concurrent ADC.
- For previously radiated lesions, the 24-month risk of necrosis was 42% with concurrent ADC versus 9.4% without concurrent ADC.
- Grade 4-5 symptomatic radiation necrosis following stereotactic radiotherapy was observed in 7.1% of brain metastases treated with concurrent ADC versus 0.7% treated without concurrent ADC. There was no difference in risk between different ADC agents.
IN PRACTICE:
On the basis of current findings, the researchers concluded that “clinicians should be cognizant of the [symptomatic radiation necrosis] risk and monitor patients closely when treating concurrently with ADCs.”
SOURCE:
The study, with first author Emily S. Lebow, MD, of Memorial Sloan Kettering Cancer Center in New York, was published online in JAMA Oncology.
LIMITATIONS:
Limitations include the retrospective study design as well as uncertainty in discriminating between radiation necrosis and local treatment failure.
DISCLOSURES:
The study had no specific funding. Four of the six authors reported various relationships with industry.
A version of this article first appeared on Medscape.com.
TOPLINE:
, a new retrospective study suggests.
METHODOLOGY:
- Stereotactic radiotherapy is a key treatment for patients with brain metastases, but some develop radiation necrosis. Because ADCs can help shrink brain metastases as well, the researchers wanted to see whether adding an ADC to stereotactic radiotherapy increased patients’ risk of symptomatic radiation necrosis.
- The study included 98 patients (84% women; median age, 55 years) with brain metastases who received at least one course of stereotactic radiotherapy for intact brain metastases and at least one dose of trastuzumab emtansine, trastuzumab deruxtecan, or sacituzumab govitecan.
- Stereotactic radiotherapy was considered concurrent with ADC therapy if delivered within 7 days before the ADC or within 21 days after the ADC. The control cohort included patients with brain metastases treated sequentially with stereotactic radiotherapy and an ADC.
- Symptomatic radiation necrosis was the primary outcome, and the researchers used competing risks regression models to analyze the impact of concurrent therapy.
TAKEAWAY:
- For the entire cohort, the 24-month cumulative incidence of symptomatic radiation necrosis was 8.5%. ADC therapy given concurrently with stereotactic radiotherapy was associated with higher risk for symptomatic radiation necrosis in univariable analysis (subdistribution hazard ratio, 4.01) and multivariable analysis (SHR, 4.31) that controlled for prior radiotherapy and volume of brain metastases.
- The risk of symptomatic radiation necrosis with concurrent ADC was modest for patients with small brain metastases who received a first course of stereotactic radiotherapy but was substantial for those with larger and reirradiated lesions treated with concurrent ADC.
- For previously radiated lesions, the 24-month risk of necrosis was 42% with concurrent ADC versus 9.4% without concurrent ADC.
- Grade 4-5 symptomatic radiation necrosis following stereotactic radiotherapy was observed in 7.1% of brain metastases treated with concurrent ADC versus 0.7% treated without concurrent ADC. There was no difference in risk between different ADC agents.
IN PRACTICE:
On the basis of current findings, the researchers concluded that “clinicians should be cognizant of the [symptomatic radiation necrosis] risk and monitor patients closely when treating concurrently with ADCs.”
SOURCE:
The study, with first author Emily S. Lebow, MD, of Memorial Sloan Kettering Cancer Center in New York, was published online in JAMA Oncology.
LIMITATIONS:
Limitations include the retrospective study design as well as uncertainty in discriminating between radiation necrosis and local treatment failure.
DISCLOSURES:
The study had no specific funding. Four of the six authors reported various relationships with industry.
A version of this article first appeared on Medscape.com.
TOPLINE:
, a new retrospective study suggests.
METHODOLOGY:
- Stereotactic radiotherapy is a key treatment for patients with brain metastases, but some develop radiation necrosis. Because ADCs can help shrink brain metastases as well, the researchers wanted to see whether adding an ADC to stereotactic radiotherapy increased patients’ risk of symptomatic radiation necrosis.
- The study included 98 patients (84% women; median age, 55 years) with brain metastases who received at least one course of stereotactic radiotherapy for intact brain metastases and at least one dose of trastuzumab emtansine, trastuzumab deruxtecan, or sacituzumab govitecan.
- Stereotactic radiotherapy was considered concurrent with ADC therapy if delivered within 7 days before the ADC or within 21 days after the ADC. The control cohort included patients with brain metastases treated sequentially with stereotactic radiotherapy and an ADC.
- Symptomatic radiation necrosis was the primary outcome, and the researchers used competing risks regression models to analyze the impact of concurrent therapy.
TAKEAWAY:
- For the entire cohort, the 24-month cumulative incidence of symptomatic radiation necrosis was 8.5%. ADC therapy given concurrently with stereotactic radiotherapy was associated with higher risk for symptomatic radiation necrosis in univariable analysis (subdistribution hazard ratio, 4.01) and multivariable analysis (SHR, 4.31) that controlled for prior radiotherapy and volume of brain metastases.
- The risk of symptomatic radiation necrosis with concurrent ADC was modest for patients with small brain metastases who received a first course of stereotactic radiotherapy but was substantial for those with larger and reirradiated lesions treated with concurrent ADC.
- For previously radiated lesions, the 24-month risk of necrosis was 42% with concurrent ADC versus 9.4% without concurrent ADC.
- Grade 4-5 symptomatic radiation necrosis following stereotactic radiotherapy was observed in 7.1% of brain metastases treated with concurrent ADC versus 0.7% treated without concurrent ADC. There was no difference in risk between different ADC agents.
IN PRACTICE:
On the basis of current findings, the researchers concluded that “clinicians should be cognizant of the [symptomatic radiation necrosis] risk and monitor patients closely when treating concurrently with ADCs.”
SOURCE:
The study, with first author Emily S. Lebow, MD, of Memorial Sloan Kettering Cancer Center in New York, was published online in JAMA Oncology.
LIMITATIONS:
Limitations include the retrospective study design as well as uncertainty in discriminating between radiation necrosis and local treatment failure.
DISCLOSURES:
The study had no specific funding. Four of the six authors reported various relationships with industry.
A version of this article first appeared on Medscape.com.