On the heels of a big breakthrough — a spinal fluid (CSF) test for Parkinson’s, or alpha-synuclein seed amplification assay (α-syn SAA in CSF) — The Michael J. Fox Foundation for Parkinson’s Research (MJFF) has announced another. This time, it’s a possible skin test for Parkinson’s disease (PD).
Recently, the National Institutes of Health (NIH) supported a multicenter study evaluating skin biopsy in 428 people with PD and related disorders as well as 120 control volunteers. Results showed the test was very accurate. In scientific terms, it had an overall 95.5 percent sensitivity (positive in people diagnosed with disease) and 96.7 percent specificity (negative in people not diagnosed with disease). In those with Parkinson’s, sensitivity was 92.7 percent. The test was also well-tolerated with minimal side effects, such as bleeding. These results have not yet been published in a peer-reviewed journal but were presented at the April 2023 American Academy of Neurology annual meeting.
Here’s what MJFF has shared about the skin test:
Researchers recently shared results of a Parkinson’s skin test that can, with high accuracy, identify abnormal protein in the skin. This protein — alpha-synuclein — is the hallmark of Parkinson’s and related disorders, like Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB). It’s a protein we all, disease or not, have. It helps nerves and other cells communicate. But in PD, alpha-synuclein changes shape, misfolds and clumps, clogging cells and impacting their ability to work. Previously, this misfolded protein could only be seen in the brain at autopsy. But with recent advances, researchers can now detect abnormal alpha-synuclein in both spinal fluid and skin. And ongoing work aims to measure the protein in blood and other tissues, like the lining of the nose and salivary gland, as well as to visualize it in the living brain.
What does the Parkinson’s skin test involve?
The test involves three small tissue samples (biopsies) from the skin of the neck, thigh and ankle. The tissue is sent to a lab, where it’s treated with a tool that stains, or highlights, abnormal alpha-synuclein. Doctors look for this highlighted protein using a microscope. They also look for other helpful information, such as how many nerve (feeling, or sensory) fibers are present and whether they’re damaged.
What will the skin test reveal?
The test tells whether, at the time it’s done, a person has abnormal alpha-synuclein in their skin. It can point, generally, toward or away from Parkinson’s and other diseases of alpha-synuclein, like MSA or DLB. It cannot yet, on its own or in a person without symptoms, diagnose or predict a specific disease. Your doctor must interpret the results in the context of your symptoms and physical examination to confirm or rule out a suspected disease.
Will the Parkinson’s skin test change how PD is diagnosed?
The diagnosis of PD remains clinical — not based on a test, but on your medical history and an expert doctor’s examination. Only when a person has the cardinal motor symptoms of Parkinson’s — slowness plus tremor or stiffness — can a diagnosis be made. The test doesn’t change that yet. But soon, the skin test, like α-syn SAA in CSF and others in the pipeline, will, hopefully, transform how and when doctors can diagnose and care for disease.
These tests also give us the first glimpses of disease biology — what’s happening in the cells of people with PD — during life (vs. at autopsy). They’re also uncovering how and why symptoms and progression differ from person to person. These tests should lead to better understanding of the disease and, ultimately, toward more personalized treatment.
Will this test change research?
Like α-syn SAA in CSF, it already is! These tests help ensure “the right people get into the right trials.” Many trials are testing therapies against alpha-synuclein with the goal of slowing Parkinson’s disease change over time. These tests can confirm research volunteers have abnormal alpha-synuclein and, in doing so, give more confidence in results. If an alpha-synuclein drug study is negative, for example, researchers can be sure it’s because an intervention didn’t work. They aren’t left wondering if, perhaps, some participants didn’t have the protein of interest so the drug might not help, regardless.
What does it mean for me?
Like α-syn SAA in CSF, this is a promising development in the field. It has immediate and broad implications for research and more efficient clinical trial testing. And it will likely have widespread effects on diagnosis, care and prognosis of Parkinson’s and related disease in the future. For now, if you’re considering one of these tests, meet with a movement disorder specialist who can talk you through the pros, cons and limitations of today’s testing.
