Tear proteins seen as Parkinson’s biomarker

The tears of people with established Parkinson’s disease have protein signatures distinct from those of healthy controls, researchers have learned.

Mark Lew, MD, and his colleagues at the University of Southern California, Los Angeles, used a noninvasive method to collect the tears and readily available assays to detect the proteins, paving the way for future studies of these proteins as biomarkers in early Parkinson’s disease (PD).

The researchers will report on their study at the annual meeting of the American Academy of Neurology in Los Angeles on April 22.

This research from Dr. Lew and his colleagues joins a host of ongoing efforts to find biomarkers for PD that can be used in the early stages of the disease, before motor dysfunction occurs. Other research groups are working on biomarkers in saliva and salivary glands, skin, blood, and cerebrospinal fluid. “Right now, a diagnosis of Parkinson’s disease is based on clinical history and then examination and then, potentially, on response to medication,” said Dr. Lew, professor of neurology, the vice chair of the department of neurology, and the director of the division of movement disorders at USC. “The difficulty is really being able to definitively be able to diagnose patients with early disease.”

Dr. Lew and his coinvestigators measured the levels of the protein alpha-synuclein in the tears of 55 people with PD and compared them with levels in the tears of 27 age- and sex-matched controls. They also measured oligomeric alpha-synuclein, an abnormal form of the protein whose aggregates are implicated in nerve damage in PD.

The test administered is based on a Schirmer’s test, which is used in ophthalmology to measure tear production. A strip of paper is placed in the lower eyelid pouch to collect tears, which the researchers then can analyze using commercially available assays.

Dr. Lew and his colleagues found levels of the oligomeric form of alpha-synuclein to be significantly greater in PD patients than they were in controls: an average of 1.45 ng/mg of tear protein, compared with 0.27 ng/mg in controls (P = .0007).

Total alpha-synuclein was decreased significantly in PD patients relative to healthy controls.

While the team looked at the levels of two additional proteins, CC chemokine ligand 2 and DJ-1 (Parkinson’s disease protein 7), neither of them varied significantly between PD patients and non-PD controls.

“We’re cautiously optimistic, and I don’t want to overstate the results because it’s still a relatively small group of subjects – we need to more than double the control population to make sure our results are maintained,” Dr. Lew said in an interview in advance of the meeting. “But it’s very exciting.”

At AAN, Dr. Lew’s research group will present findings from a larger cohort of both patients and controls. “Our expectation is that things will look similar and we will continue to see a significant difference in the oligomeric form of alpha-synuclein,” the tear protein associated with PD.

The idea of using tear proteins as biomarkers for PD came as a result of a collaboration with scientists working in USC’s ophthalmology lab, who had previously worked on tear biomarkers in other disorders, including Sjogren’s syndrome, Dr. Lew said.

Dr. Lew said that, if the initial results bear out in a larger cohort, the next step is to test the tears of people with genetic or atypical forms of PD and compare the results with those for idiopathic forms. “These atypical forms, like progressive supranuclear palsy [PSP] and multiple system atrophy [MSA], can be very difficult to tell apart clinically in the early stages. If we had a simple test to do that, it would be very helpful.”

A reliable biomarker, if it can be shown to be sensitive early in disease, also would have implications for the timing of disease-modifying interventions, such as the monoclonal antibodies or gene therapies that are currently being investigated.

“We don’t have those therapies now, but in a few years we very well could,” Dr. Lew said. “If we could identify patients early and if we had a therapy that we could give them that was disease-modifying, or neuroprotective, you’d want to start much earlier than we currently do.”

This study from Dr. Lew and his colleagues was supported by the Michael J. Fox Foundation and the Plotkin Foundation. Dr. Lew has received personal compensation for consulting for, serving on a scientific advisory board for, speaking for, or other activities with Teva Pharmaceutical Industries, US WorldMeds, AbbVie, Lundbeck, Acadia Pharmaceuticals, UCB, Revance Therapeutics, and Adamas Pharmaceuticals. Dr. Lew has received research support from Acorda Therapeutics, Biotie Therapies, NeuroDerm, and Lilly. None of the other authors had anything to disclose.

SOURCE: Feigenbaum D et al. Abstract 4209.

The tears of people with established Parkinson’s disease have protein signatures distinct from those of healthy controls, researchers have learned.

Mark Lew, MD, and his colleagues at the University of Southern California, Los Angeles, used a noninvasive method to collect the tears and readily available assays to detect the proteins, paving the way for future studies of these proteins as biomarkers in early Parkinson’s disease (PD).

The researchers will report on their study at the annual meeting of the American Academy of Neurology in Los Angeles on April 22.

This research from Dr. Lew and his colleagues joins a host of ongoing efforts to find biomarkers for PD that can be used in the early stages of the disease, before motor dysfunction occurs. Other research groups are working on biomarkers in saliva and salivary glands, skin, blood, and cerebrospinal fluid. “Right now, a diagnosis of Parkinson’s disease is based on clinical history and then examination and then, potentially, on response to medication,” said Dr. Lew, professor of neurology, the vice chair of the department of neurology, and the director of the division of movement disorders at USC. “The difficulty is really being able to definitively be able to diagnose patients with early disease.”

Dr. Lew and his coinvestigators measured the levels of the protein alpha-synuclein in the tears of 55 people with PD and compared them with levels in the tears of 27 age- and sex-matched controls. They also measured oligomeric alpha-synuclein, an abnormal form of the protein whose aggregates are implicated in nerve damage in PD.

The test administered is based on a Schirmer’s test, which is used in ophthalmology to measure tear production. A strip of paper is placed in the lower eyelid pouch to collect tears, which the researchers then can analyze using commercially available assays.

Dr. Lew and his colleagues found levels of the oligomeric form of alpha-synuclein to be significantly greater in PD patients than they were in controls: an average of 1.45 ng/mg of tear protein, compared with 0.27 ng/mg in controls (P = .0007).

Total alpha-synuclein was decreased significantly in PD patients relative to healthy controls.

While the team looked at the levels of two additional proteins, CC chemokine ligand 2 and DJ-1 (Parkinson’s disease protein 7), neither of them varied significantly between PD patients and non-PD controls.

“We’re cautiously optimistic, and I don’t want to overstate the results because it’s still a relatively small group of subjects – we need to more than double the control population to make sure our results are maintained,” Dr. Lew said in an interview in advance of the meeting. “But it’s very exciting.”

At AAN, Dr. Lew’s research group will present findings from a larger cohort of both patients and controls. “Our expectation is that things will look similar and we will continue to see a significant difference in the oligomeric form of alpha-synuclein,” the tear protein associated with PD.

The idea of using tear proteins as biomarkers for PD came as a result of a collaboration with scientists working in USC’s ophthalmology lab, who had previously worked on tear biomarkers in other disorders, including Sjogren’s syndrome, Dr. Lew said.

Dr. Lew said that, if the initial results bear out in a larger cohort, the next step is to test the tears of people with genetic or atypical forms of PD and compare the results with those for idiopathic forms. “These atypical forms, like progressive supranuclear palsy [PSP] and multiple system atrophy [MSA], can be very difficult to tell apart clinically in the early stages. If we had a simple test to do that, it would be very helpful.”

A reliable biomarker, if it can be shown to be sensitive early in disease, also would have implications for the timing of disease-modifying interventions, such as the monoclonal antibodies or gene therapies that are currently being investigated.

“We don’t have those therapies now, but in a few years we very well could,” Dr. Lew said. “If we could identify patients early and if we had a therapy that we could give them that was disease-modifying, or neuroprotective, you’d want to start much earlier than we currently do.”

This study from Dr. Lew and his colleagues was supported by the Michael J. Fox Foundation and the Plotkin Foundation. Dr. Lew has received personal compensation for consulting for, serving on a scientific advisory board for, speaking for, or other activities with Teva Pharmaceutical Industries, US WorldMeds, AbbVie, Lundbeck, Acadia Pharmaceuticals, UCB, Revance Therapeutics, and Adamas Pharmaceuticals. Dr. Lew has received research support from Acorda Therapeutics, Biotie Therapies, NeuroDerm, and Lilly. None of the other authors had anything to disclose.

SOURCE: Feigenbaum D et al. Abstract 4209.

The tears of people with established Parkinson’s disease have protein signatures distinct from those of healthy controls, researchers have learned.

Mark Lew, MD, and his colleagues at the University of Southern California, Los Angeles, used a noninvasive method to collect the tears and readily available assays to detect the proteins, paving the way for future studies of these proteins as biomarkers in early Parkinson’s disease (PD).

The researchers will report on their study at the annual meeting of the American Academy of Neurology in Los Angeles on April 22.

This research from Dr. Lew and his colleagues joins a host of ongoing efforts to find biomarkers for PD that can be used in the early stages of the disease, before motor dysfunction occurs. Other research groups are working on biomarkers in saliva and salivary glands, skin, blood, and cerebrospinal fluid. “Right now, a diagnosis of Parkinson’s disease is based on clinical history and then examination and then, potentially, on response to medication,” said Dr. Lew, professor of neurology, the vice chair of the department of neurology, and the director of the division of movement disorders at USC. “The difficulty is really being able to definitively be able to diagnose patients with early disease.”

Dr. Lew and his coinvestigators measured the levels of the protein alpha-synuclein in the tears of 55 people with PD and compared them with levels in the tears of 27 age- and sex-matched controls. They also measured oligomeric alpha-synuclein, an abnormal form of the protein whose aggregates are implicated in nerve damage in PD.

The test administered is based on a Schirmer’s test, which is used in ophthalmology to measure tear production. A strip of paper is placed in the lower eyelid pouch to collect tears, which the researchers then can analyze using commercially available assays.

Dr. Lew and his colleagues found levels of the oligomeric form of alpha-synuclein to be significantly greater in PD patients than they were in controls: an average of 1.45 ng/mg of tear protein, compared with 0.27 ng/mg in controls (P = .0007).

Total alpha-synuclein was decreased significantly in PD patients relative to healthy controls.

While the team looked at the levels of two additional proteins, CC chemokine ligand 2 and DJ-1 (Parkinson’s disease protein 7), neither of them varied significantly between PD patients and non-PD controls.

“We’re cautiously optimistic, and I don’t want to overstate the results because it’s still a relatively small group of subjects – we need to more than double the control population to make sure our results are maintained,” Dr. Lew said in an interview in advance of the meeting. “But it’s very exciting.”

At AAN, Dr. Lew’s research group will present findings from a larger cohort of both patients and controls. “Our expectation is that things will look similar and we will continue to see a significant difference in the oligomeric form of alpha-synuclein,” the tear protein associated with PD.

The idea of using tear proteins as biomarkers for PD came as a result of a collaboration with scientists working in USC’s ophthalmology lab, who had previously worked on tear biomarkers in other disorders, including Sjogren’s syndrome, Dr. Lew said.

Dr. Lew said that, if the initial results bear out in a larger cohort, the next step is to test the tears of people with genetic or atypical forms of PD and compare the results with those for idiopathic forms. “These atypical forms, like progressive supranuclear palsy [PSP] and multiple system atrophy [MSA], can be very difficult to tell apart clinically in the early stages. If we had a simple test to do that, it would be very helpful.”

A reliable biomarker, if it can be shown to be sensitive early in disease, also would have implications for the timing of disease-modifying interventions, such as the monoclonal antibodies or gene therapies that are currently being investigated.

“We don’t have those therapies now, but in a few years we very well could,” Dr. Lew said. “If we could identify patients early and if we had a therapy that we could give them that was disease-modifying, or neuroprotective, you’d want to start much earlier than we currently do.”

This study from Dr. Lew and his colleagues was supported by the Michael J. Fox Foundation and the Plotkin Foundation. Dr. Lew has received personal compensation for consulting for, serving on a scientific advisory board for, speaking for, or other activities with Teva Pharmaceutical Industries, US WorldMeds, AbbVie, Lundbeck, Acadia Pharmaceuticals, UCB, Revance Therapeutics, and Adamas Pharmaceuticals. Dr. Lew has received research support from Acorda Therapeutics, Biotie Therapies, NeuroDerm, and Lilly. None of the other authors had anything to disclose.

SOURCE: Feigenbaum D et al. Abstract 4209.