AAN 2023: Skin test ably detects alpha-synuclein clumps in trial

Via biopsies, evidence of Parkinson's seen in more than 92% of study's patients

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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An illustration for the AAN conference showing a nerve cell.

An assay using skin biopsies, called the Syn-One Test, was able to detect the alpha-synuclein protein that characterizes Parkinson’s disease and like conditions in more than 90% of the patients enrolled in a clinical trial.

“These results validate cutaneous [skin-based] alpha-synuclein as a reliable biomarker for Parkinson’s disease and related disorders, allowing us to offer the Syn-One Test as an accessible, patient-friendly diagnostic solution for clinical practice and … trials targeting alpha-synuclein,” Todd Levine, MD, chief medical officer of CND Life Sciences, the test’s developer, said in a company press release.

Christopher Gibbons, MD, senior scientific advisor at CND, presented these findings at the American Academy of Neurology (AAN)’s recent annual meeting, in the talk, “The Synuclein-One Study: Skin Biopsy Detection of Phosphorylated alpha-synuclein for Diagnosis of the Synucleinopathiesm.” The study was sponsored by the National Institutes of Health (NIH).

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In this illustration for the American Academy of Neurology annual meeting, an older woman is seen walking with the help of a cane.

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Trial enrolled 96 Parkinson’s patients, 127 people with other synucleinopathies

“These findings provide immediate benefit to patient care and will help advance novel drug development for neurodegenerative diseases,” said Gibbons, who is also a neurologist with Beth Israel Deaconess Medical Center in Boston.

Parkinson’s disease is marked by the formation of aggregates, or clumps, of alpha-synuclein in brain cells. These protein clumps are toxic to cells and are thought to be a major driver of disease progression.

Clumps of alpha-synuclein in the brain are also characteristic of rarer conditions, including dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and pure autonomic failure (PAF). Collectively, these disorders are known as synucleinopathies.

Despite the suspected role of alpha-synuclein aggregates in disease, current technologies cannot reliably detect these clumps in the brains of living people.

“Finding an easily accessible and reliable clinical tool” to diagnose Parkinson’s and other synucleinopathies “has really been an urgent, unmet priority,” Gibbons said.

In the Syn-One Test, a physician collects biopsies of a patient’s skin from three points on the body, at the neck, thigh, and calf. The procedure is minimally invasive and usually takes about 15 minutes, the company reports. Samples then are sent to a laboratory for analysis to see whether alpha-synuclein is detectable in skin nerve fibers.

The Synuclein-One Study (NCT04700722) is a clinical trial funded by the NIH to understand whether this test could be used to detect disease-associated alpha-synuclein. The primary analysis included 96 people with Parkinson’s, as well as 127 people with other types of synucleinopathies, and 120 people with no known neurological disease.

Results showed that the Syn-One Test was positive in 95.5% of patients with synucleinopathies, whereas the test was negative in 96.7% of the people without such disease — working out to a total overall accuracy of 95.9%. Among Parkinson’s patients specifically, 92.7% were positive, and the test’s overall accuracy was 94.9%.

“No study has ever demonstrated higher sensitivity and specificity across the synucleinopathies, including those using spinal fluid,” Levine said.

Skin tissue seen as ‘unique window into the central nervous system’

Gibbons noted that the amount of detected alpha-synuclein tended to vary across the diseases, and at the different biopsy sites tested. Generally, Parkinson’s patients had lower detected levels of the protein than patients with other synucleinopathies, and neck biopsy samples showed higher levels than leg samples in people with Parkinson’s.

“The results confirm a decade of research demonstrating that nerves in the skin serve as a unique window into the central nervous system and support the thesis that distinct synuclein deposition signatures and other cutaneous markers can differentiate among the synucleinopathies,” Gibbons said.

The diagnostic test was generally safe. Two patients experienced some minor bleeding at biopsy sites, but no other noteworthy safety findings were reported.

“Skin biopsies are a simple, low-risk, outpatient procedure to test for phosphorylated alpha-synuclein as a diagnostic biomarker,” Gibbons said. Phosphorylated alpha-synuclein is the version of the protein most prone to clumping.

“With a minimally invasive skin-based test like Syn-One, we can offer our patients a higher degree of confidence and accuracy in the diagnosis of Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy, and differentiate these disorders from other neurodegenerative diseases,” said Joseph Jankovic, MD, a professor of neurology at Baylor College of Medicine. “This will change how many of these patients are evaluated and treated.”

Note: The Parkinson’s News Today team is providing coverage of the American Academy of Neurology (AAN) 2023 Annual Meeting April 22-27. Go here to see the latest stories from the conference.