It may be possible to diagnose Parkinson’s disease with a skin test, a new study suggests.
For the study, researchers used a chemical assay to detect clumping of the protein alpha-synuclein, a hallmark of Parkinson’s disease, in autopsy skin samples taken from patients who had Parkinson’s disease confirmed by brain pathology and from controls without the disease. The test showed a high degree of sensitivity and specificity for the diagnosis of Parkinson’s.
The study was published online in the scientific journal Movement Disorders.
“This test has a lot of promise,” senior author Anumantha Kanthasamy, PhD, professor of biomedical sciences at Iowa State University in Ames, told Medscape Medical News.
“At present there are no peripheral biomarkers for Parkinson’s disease. The current diagnosis is just based on symptoms and the symptoms can be similar to many other neurological diseases,” he added. “It can take many years to establish a correct diagnosis and the accuracy is low even with experienced neurologists.”
If the current results can be replicated in samples from live patients and in those with very early stages of Parkinson’s, a skin test could allow early diagnosis and the possibility of starting preventive treatments to slow disease progression before symptoms develop too severely, the researchers suggest.
The blinded study used a seeding assay — used previously to detect misfolded proteins in prion diseases — to analyze 50 skin samples provided by the Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program based at Banner Sun Health Research Institute.
Half of the skin samples came from patients with Parkinson’s disease and half came from people without neurologic disease. The protein assay correctly diagnosed 24 out of 25 Parkinson’s disease patients and only one of the 25 controls had the protein clumping.
“At present, the only way to definitely diagnose Parkinson’s disease is on autopsy — by the detection of alpha synuclein clumps (Lewy bodies) in the brain,” Charles Adler, MD, professor of neurology at Mayo Clinic Arizona in Scottsdale and a co-investigator of the study, commented to Medscape Medical News. “In our research, we have also seen clumping of alpha synuclein in many other organs including submandibular gland, colon, skin, heart, and stomach, but in terms of access, the skin is probably the easiest source.”
In this study, “we found this seeding assay for alpha synuclein clumps to be extremely sensitive and specific in the diagnosis of Parkinson’s,” he added. “This is very valuable data as we have samples from autopsy-validated Parkinson’s patients.”
The researchers are now starting a study in living patients with funding from the National Institutes of Health in which they will repeat the process comparing skin samples from patients with clinically diagnosed PD and controls.
“We need to know whether analyzing alpha-synuclein clumping in skin biopsies from live Parkinson’s patients would serve as a reliable biomarker for disease progression. Will clumping of this protein in skin samples increase over time and does it correspond with disease progression?” Adler said.
In future they are also hoping to test individuals who have not yet developed Parkinson’s disease but may have some prodromal type symptoms, and to test whether this assay could measure a treatment effect of drug therapy.
Adler noted that they are currently conducting an autopsy study of skin samples from individuals who did not have clinical Parkinson’s disease when alive but in whom Lewy bodies have been found postmortem.
“This suggests that the disease pathology starts before Parkinson’s symptoms develop, and in the future, if we can diagnose Parkinson’s earlier then we may be able to stop progression,” he said.
“There is a long list of compounds that have been studied to try and slow progression but haven’t shown benefits, but by the time patients develop symptoms they already have significant disease and [have] lost most of their dopamine neurons,” he added. “If we could backtrack by 10 years, then these drugs may well make a difference.”
Adler also noted that currently more advanced patients may undergo invasive procedures such as deep brain stimulation or surgery. “It is of utmost importance that they have an accurate diagnosis before being subjected to such procedures.”
In addition, he pointed out that an accurate test would help the drug development process. “It is vitally important to enroll patients with an accurate diagnosis in clinical trials of new drugs. At present, a large percentage of patients in these trials may not actually have Parkinson’s disease, which makes it very difficult to show a treatment effect.”
Important Step, but Preliminary
Commenting for Medscape Medical News, James Beck, PhD, chief scientific officer of the Parkinson’s Foundation, said the study “is an important step toward the creation of a new way to potentially diagnose Parkinson’s disease.”
But he cautioned that this is a preliminary study. “To really confirm the possibility of using this approach for diagnosing Parkinson’s, a larger study will be necessary. And it will be important to test this in a population with early disease — the most difficult group to accurately diagnose.”
Also commenting on the findings, Beate Ritz, MD, PhD, an epidemiologist at UCLA Fielding School of Public Health in Los Angeles, who is part of a team also working on ways to measure abnormal alpha-synuclein to diagnose Parkinson’s, described the current study of skin samples as “pretty nifty.”
“Their research shows clearly that they can distinguish between Parkinson’s patients and controls in this way,” she said. “The big advantage of this study is that they have brain pathology, so they know exactly which individuals had Parkinson’s.”
Ritz is working with Gal Bitan, PhD, from the UCLA Brain Research Institute on a potential blood test to measure abnormal alpha-synuclein.
She explained that it is not possible to measure alpha-synuclein pathology in regular blood samples as it is expressed normally in red blood cells, but they are measuring the protein and its more toxic phosphorylated form from exosomes, which contain the waste discarded by cells using technology that determines the origin of these exosomes.
“Alpha-synuclein itself is not a problem. It is the way it misfolds that causes toxicity and disrupts the workings of the cell,” Ritz added. “In Parkinson’s, it is particularly toxic to dopaminergic neurons, and in multiple system atrophy, it is toxic to glial cells, so if we can identify the source of the protein then that could be helpful.”
The study was funded by the National Institutes of Health and the US Army Medical Research Materiel Command. The study authors, Beck, and Ritz have disclosed no relevant financial relationships.
Movement Disorders. Published online September 22, 2020. Abstract