Todd Levine, MD, on the Syn-One Test and Its Role in Neurodgenerative Disorder Diagnosis

Todd Levine, MD

At the 2023 American Academy of Neurology (AAN) Annual Meeting, April 22-27, in Boston, Massachusetts, topline data were presented from the Synuclein-One Study of CND Life Sciences’ Syn-One Test, suggesting its sensitivity and specificity for the detection of phosphorylated α-synuclein is clinically relevant and useful.¹

The test is an α-synuclein skin biopsy test used for the detection of the pathology in Parkinson disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and pure autonomic failure (PAF). Across all patients with clinically diagnosed synucleinopathy, the test’s sensitivity was 95.5% and specificity—derived from healthy controls—was 96.7%. Among the various synucleinopathies included, the specific sensitivity rates were 92.7% with PD, 98.2% with MSA, 96.0% with DLB, and 100.0% with PAF.

In addition to its promising detection results, the test was deemed safe and tolerable, with only minimal, Grade 1 nonserious adverse events (AEs) reported in 0.4% of participants. That AE was minor bleeding from the biopsy site. No Grade 2 or 3 AEs were observed.

To further contextualize the study findings and the utility of this test—which CND noted has been ordered by more than 500 neurologists in the United States—NeurologyLive^® inquired briefly with Todd Levine, MD, the chief medical officer and cofounder of CND Life Sciences, who served as principal investigator of the study.

NeurologyLive: How important is the Syn-One Test in clinical diagnosis of PD? Can it aid in earlier detection of PD and other disorders?

Todd Levine, MD: Parkinson disease overlaps clinically with several other conditions, particularly early in the disease course. Some patients can have Parkinsonism from medications, or from other diseases like progressive supranuclear palsy, or complex essential tremor progression. The Syn-One Test is highly accurate in identifying the phosphorylated alpha-synuclein to confirm Parkinson disease and distinguish it from these other nonsynuclein related conditions.

The ability to visualize this synuclein accumulation directly within the nerve is what makes this test so helpful even early in the disease course. Previously reported work in patients with isolated REM sleep behavior disorder have confirmed that phosphorylated alpha-synuclein can be detected in the skin prior to the typical motor manifestations of Parkinson’s disease with relatively high levels of sensitivity (85% to 90%).^2,3

In addition to the high level of sensitivity and specificity, the Syn-One Test has significant ease-of-use advantages over other testing modalities like spinal tap and imaging. This has been evident in the rapid growth of Syn-One over the last 3 years with nearly 10,000 tests performed by nearly 700 neurologists.

How far does the potential of such a test stretch in terms of the number of diseases/conditions for which it might be applicable?

The Syn-One Test is the easiest and most sensitive way to detect and visualize the misfolded form of alpha-synuclein. This means it can help diagnose not just Parkinson’s disease, but also dementia with Lewy bodies, multiple system atrophy, pure autonomic failure, and REM behavior disorder. Doctors throughout the country have been using this test for the past 3 years to help diagnose patients with these conditions. A positive test helps to rule out nonsynuclein based disorders such as progressive supranuclear palsy, essential tremor, medication induced Parkinsonism and other related conditions.

We also continue to publish encouraging findings that the Syn-One Test can reveal distinct “synuclein signatures” in the skin that may help us differentiate among the synucleinopathies, including PD vs MSA vs DLB. These are very promising findings that we plan to further investigate and know practicing physicians would find useful in their care of patients.

Transcript edited for clarity. Click here for more coverage of AAN 2023.

REFERENCES
1. Gibbons C, Levine T, Bellaire B, et al. The Synuclein-One Study: Skin Biopsy Detection of Phosphorylated alpha-synuclein for Diagnosis of the Synucleinopathies. Presented at: AAN Annual Meeting; April 22-27, 2023; Boston, MA and Virtual. Presentation 6545.
2. Liguori R, Donadio V, Wang Z et al. A comparative blind study between skin biopsy and seed amplification assay to disclose pathological α-synuclein in RBD. NPJ Parkinsons Dis. 2023;9(1):34. doi:10.1038/s41531-023-00473-5
3. Miglis MG, Zitser J, Schneider L, et al. Cutaneous α-synuclein is correlated with autonomic impairment in isolated rapid eye movement sleep behavior disorder. Sleep. 2021;44(12):zsab172. doi: 10.1093/sleep/zsab172. PMID: 34244806