Syn-One Test Reports High Sensitivity and Specificity Across Multiple Synucleinopathies

Christopher H. Gibbons, MD, FAAN

Topline data from the Synuclein-One Study of CND Life Sciences’ Syn-One Test, 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), suggest that the test is sensitive and specific in said detection of phosphorylated α-synuclein.^1,2 As misdiagnosis remains a consistent challenge in neurodegenerative disorders—some estimates suggest a misdiagnosis rate of 30%³—this represents an opportunity to address this clinical obstacle.

All told, 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. Among those who were clinically diagnosed, 214 tests were positive and 10 were negative; among healthy controls, 4 tests were positive and 116 were negative.

The results of the study were presented at the 2023 American Academy of Neurology (AAN) Annual Meeting, April 22-27, in Boston, Massachusetts, by Christopher H. Gibbons, MD, FAAN, the study’s lead author and senior scientific advisor to CND Life Sciences, who is also an associate professor of neurology at Harvard Medical School and the director of the Joslin Diabetes Center Neuropathy Clinic and the neurocutaneous skin biopsy lab at Beth Israel Deaconess Medical Center. 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. These findings provide immediate benefit to patient care and will help advance novel drug development for neurodegenerative diseases,” Gibbons said in a statement.²

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"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," Todd Levine, MD, chief medical officer of CND Life Sciences and the principal investigator of the study, told NeurologyLive^®. "These are very promising findings that we plan to further investigate and know practicing physicians would find useful in their care of patients."

The study included 428 patients in total—108 with PD, 69 with MSA, 67 with DLB, 33 with PAF, and 151 healthy controls—with the primary analysis including 343 of these individuals and a secondary analysis including 85 individuals. At baseline, those with PD, MSA, DLB, and PAF were 70 (±8), 67.3 (±8.9), 75.1 (±8.1), and 71.6 (±7.7) years of age, respectively, with mean Unified Parkinson’s Disease Rating Scale (UPDRS) Part II scores of 8.5 (±7.5), 23.5 (±12.2), 15.7 (±10.6), and 5.8 (±6.6), respectively. The healthy control group, on the other hand, had a mean age of 59.5 years (±11.1) and a mean UPDRS-II score of 0.2 (±0.8).

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.

“No study has ever demonstrated higher sensitivity and specificity across the synucleinopathies, including those using spinal fluid,” Levine said in a statement.² “These results validate cutaneous α-synuclein as a reliable biomarker for Parkinson disease and related disorders, allowing us to offer the Syn-One Test as an accessible, patient-friendly diagnostic solution for clinical practice and an important technology for biopharmaceutical trials targeting α-synuclein.”

According to CND Life Sceinces,² thus far, more than 10,000 of these tests have been ordered by more than 700 neurologists in the United States since 2019. The Syn-One Test analyzes 3 small skin biopsies collected from patients in an office visit, taking about 15 minutes as a minimally invasive procedure, and includes an assessment of intraepidermal nerve fiber density, among other pathologic evaluations. The study was funded by a $2.4-million phase 2 Small Business Innovation Research grant from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health.

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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. CND Life Sciences’ Syn-One Test® Detects Alpha-Synuclein in the Skin with High Sensitivity and Specificity in Patients with Parkinson’s Disease and Related Disorders. News release. CND Life Sciences. April 26, 2023. Accessed April 26, 2023.
3. Adler CH, Beach TG, Hentz JG et al. Low clinical diagnostic accuracy of early vs advanced Parkinson disease: clinicopathologic study. Neurology. 2014;83(5):406-12. doi:10.1212/WNL.0000000000000641.