Hows and Whys of Skin Biopsy Test For Parkinson’s Disease

Approximately 20% of patients clinically diagnosed with Parkinson’s disease (PD) turn out not to have the movement disorder, resulting in unnecessary treatments, medications, and procedures. “Study after study has shown that even in the best of centers, we’re wrong 1 out of 4 times,” says Stuart Isaacson, MD, the director of the Parkinson’s Disease and Movement Disorders Center of Boca Raton, Florida.

But a new skin biopsy test is taking some of the guesswork out of the process. Called Syn-One Test, it identifies a potential biomarker for PD and when combined with other evaluation methods such as gene testing and DaTscans, it can help clinicians diagnose and manage PD earlier and with greater confidence.

“This type of testing shifts the paradigm,” says Isaacson. “It really changes how we approach, counsel, and treat patients.”

How Does the Test Work?

Until recently, the cellular biology of people with PD was a mystery. Although the German neurologist, Fritz Heinrich Lewy, detected abnormal proteins in the brains of those suffering from PD back in 1912, not much was known about them.

In the past decade, research has intensified on these Lewy bodies. The Syn-One Test developed by CND Life Sciences is the only commercially available test of its kind that can detect one of the main components of Lewy bodies, a protein called alpha-synuclein (aSyn).

“When a nerve wants to talk to another nerve, it releases a neurotransmitter,” explains Todd Levine, MD, chief medical officer for CND. “In the case of depression that neurotransmitter could be serotonin or norepinephrine. In the case of PD, it would be dopamine. It’s believed aSyn regulates the release of these neurochemicals.”

“Normal aSyn is soluble,” Levine continues, “which allows it to move freely throughout the nerve and then, after its job is done, degrade and be replaced. But with PD, something causes the protein to misfold and become insoluble.” Over time, it’s believed this highly phosphorylated and abnormally aggregated aSyn (pSyn) damages the nerves, he explains.

Previously, the only methods for detecting abnormal protein were autopsy and spinal tap. The development of a simple skin biopsy test could not only enable clinicians to confirm suspicions of PD and other neurodegenerative diseases much earlier but also help pharmaceutical companies create drugs that target pSyn. (According to Levine, there are 35-40 in the pipeline.)

How Accurate Is the Test?

Results from a National Institutes of Health–supported study that evaluated skin biopsy testing were presented at the American Academy of Neurology’s annual meeting in April 2023. Researchers administered the Syn-One Test to 428 people with PD and related disorders (plus 120 control volunteers). They found the test to be very accurate, with 95.5% sensitivity (positive in those diagnosed with disease) and 96.7% specificity (negative in those not diagnosed with disease). In those with PD, sensitivity was 92.7%. A smaller CND study published in Neurology suggests the test may also be able to differentiate PD from multiple system atrophy, which can look similar in its early stages.

Overall, Levine thinks that the situation is analogous to the evolution of HIV treatment. Breakthroughs didn’t occur until there was a test to dependably measure the virus. Then, dozens of drugs were developed. Today, a doctor can accurately measure the HIV virus, prescribe a combination of drugs, measure the virus again in a few months, and then either continue the treatment or try a new one. He believes that the management of PD will follow a similar path.

Isaacson, who consults for CND, says he has used the Syn-One Test on more than 100 patients. Although it can’t diagnose PD on its own, he’s made it “a part of his diagnostic algorithm” and is pleased with the results so far. In particular, he’s found it useful for patients in three scenarios: (1) those with early symptoms of PD who want a more accurate clinical diagnosis, (2) those with a PD diagnosis who are not responding to dopamine replacement medication, and (3) those who clearly have progressive PD and may not need DaTscan testing if synuclein degeneration can be detected with a skin biopsy.

“It’s one more useful tool in the toolbox,” says Mark Frasier, PhD, chief scientific officer for the Michael J. Fox Foundation, “but I hesitate to call it a breakthrough just yet. We still need additional data on how early this test can detect positive synuclein prior to motor symptoms developing, and we need to understand better how the company quantifies the amount that’s present.”

“Nonetheless,” he continues, “the field is shifting toward how early someone with PD can be treated, and it’s going to impact clinical trial design and research in the near term.”

How Do I Get a Test Kit?

Clinicians can order Syn-One kits, which have a shelf life of 1 year, here for free. CND is licensed in all states except New York. (Doctors there can still get the kit, but they must obtain permission from their state lab first). The test takes about 15 minutes to administer and involves taking biopsies from the patient’s neck, knee, and ankle. It requires no stitches and can be done by an MD, DO, NO, or PA in the office. The samples are then sent to the CND lab in Arizona, and results are promised within 21 days.

Clinicians can bill insurance for the biopsies using established CPT codes. For the Medicare population, Levine says 80% of the test is generally paid for, which leaves about $300-$400 for the patient. “If they have a supplement or secondary insurance, then there’s very little out of pocket,” he says.

The Future

Frasier points out that there are already medicines in trials targeting synuclein along with other proteins, “so things are going to move rapidly.” With the addition of this skin test, the trials themselves can be more efficient since researchers now have one more way to confirm PD in study participants. Saliva and blood tests for abnormal proteins are also being worked on.

What else is Levine excited about? “There have been a couple of trials looking at antibodies designed to soak up the bad protein, but those have not worked yet,” he says. “There are trials with vaccines, so maybe you could be vaccinated against synuclein [degeneration] and allow your immune system to stop it. And there are small molecules being developed to help prevent the proteins from forming into blobs in the first place.”

“People are really being very clever about targeting this,” he continues. “Right now, the mainstay for PD therapy is simply symptomatic therapy. But what we really want is disease-modifying therapy, and I’m optimistic about its development.”

Mark Frasier, PhD, reported the following relevant relationships: MJFF funded the development of the test early on (about 2013), but has no financial interest in it now. Stuart Isaacson, MD, reported consulting fees and research grants from CND Life Sciences and from a number of pharmaceutical companies looking into new drugs to slow PD progression and treat symptoms. Todd Levine, MD, is the CMO and co-founder of CND Life Sciences, the manufacturer of the Syn-One Test.