Objective: To increase our understanding of the pathogenesis of atypical parkinsonian disorders though genetics, and to build a cohort of individuals for future research.

Background: The role of genetics in progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA) remains incompletely understood. Due to their rare occurrence in the general population, large cohorts are required for gene discovery efforts.

Method: The CurePSP Genetics Program started enrollment on October 8, 2024. Participants are self-referred through online advertising by the CurePSP Foundation or recruited across the U.S. by CurePSP Centers of Care and other neurological specialists who confirm the diagnosis of PSP, CBS, or MSA. A centralized coordinating center at Massachusetts General Hospital obtains informed consent, family history, and disease history. Mobile phlebotomists collect blood samples at participants’ homes and send them to the National Institutes of Health for processing and whole genome sequencing (WGS). De-identified sequencing data will be available to researchers on publicly accessible data repositories. Samples will also be shared with the Global Parkinson’s Genetics Program (GP2). If pathogenic or likely pathogenic variants are found, Clinical Laboratory Improvement Amendment (CLIA)-certified confirmation testing is performed, with genetic counseling provided to participants with positive results.

Results: The first 100 participants consented include 74 individuals with PSP, 16 with CBS, and 10 with MSA-P, 48 females and 52 males, with an average age of 70.0 (S.D. 6.9) years and a time since diagnosis of 2.4 (S.D. 2.4) years across all diseases. Participants have an average of 16.3 (S.D. 2.8) years of formal education and come from across the US including Hawaii. Of the PSP participants, 8% report a relative diagnosed with PSP and 28% have a family history of other neurological conditions (CBS, MSA, amyotrophic lateral sclerosis, frontotemporal dementia, or Alzheimer’s disease). These numbers will be updated at the time of the conference.

Conclusion: This study demonstrates the feasibility of the CurePSP Genetics Program for DNA collection from individuals with PSP, CBS, and MSA. While there may be some bias or self-selection in enrollment, this initial cohort suggests that familial inheritance may play a larger role in the pathogenesis of atypical parkinsonism than previously estimated.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/disease-characteristics-of-the-first-100-participants-in-the-curepsp-genetics-program-cohort/