Objective: The Synuclein-One study is an NIH-funded 30-site, multicenter trial of 428 patients with synucleinopathies  including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA) and pure autonomic failure (PAF). The study was designed to describe the sensitivity, specificity, accuracy and precision of cutaneous phosphorylated alpha-synuclein detection in patients with synucleinopathies. Enrollment closed in January 2023, with final data analysis by April, 2023

Background: An important unmet need exists for a validated, well-characterized, simple, reproducible marker of synuclein pathology. The number of individuals with neurodegenerative diseases continues to grow and misdiagnosis within and among synuclein and non-synuclein pathologies continues to occur, resulting in incorrect medication choices, iatrogenic complications, poor prognostication and patient frustration.

Method: After signing informed consent, all participants completed detailed neurologic examinations (MDS-UPDRS, Hoehn and Yahr scale), medical and neurological history review, cognitive evaluation (MOCA), orthostatic vital signs, RBD questionnaire, orthostatic hypotension questionnaire, MSA red flags and Parkinson’s Disease Questionnaire-39. Skin biopsies at the distal leg, distal thigh and posterior cervical sites were performed on all participants. All clinical data were reviewed by a blinded expert consensus panel to confirm the referring diagnosis or move the subject to an ‘indeterminate’ category. The Syn-One Test was performed at CND Life Sciences and the Neurocutaneous Laboratory at Beth Israel Deaconess Medical Center. Phosphorylated alpha-synuclein deposition was quantified by 2 readers, blinded to referring diagnosis and results of the other reader.

Results: Final un-blinded results will be presented at the MDS 2023 annual meeting with a focus on test sensitivity, specificity, accuracy and precision.  In addition, synucleinopathy subgroup analysis will be performed to define unique pathological characteristics of disease (PD, MSA, DLB or PAF).

Conclusion: The Synuclein-One study is the largest investigation of cutaneous phosphorylated alpha-synuclein detection across all four synucleinopathies and will advance the field of neuro-diagnostic testing in neurodegenerative disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-synuclein-one-study-detection-of-cutaneous-phosphorylated-alpha-synuclein-for-the-diagnosis-of-the-synucleinopathies/