To increase our understanding of the pathogenesis of atypical parkinsonian disorders through genetics and to build cohorts for future research.

The role of genetic factors in progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA) remains incompletely understood, due to the rarity of these diseases. Larger cohorts are needed for gene discovery efforts.

Participants are self-referred through outreach to CurePSP’s patient community and online advertising and 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 NIH 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 in genes thought to be linked PSP, CBS, or MSA, Clinical Laboratory Improvement Amendment (CLIA)-certified confirmation testing is performed.  Results disclosure and genetic counseling are provided to participants with positive results.

In the first week, 33 people registered: 23 with PSP, 4 with CBS, and 3 with MSA. Three registrants did not have these conditions and were screen-failed. Participants registered from across the US including Hawaii.  Eight (24%) registrants reported a positive family history of neurological disease. Participant numbers will be updated at the meeting including demographics and geographic location.

This study involves the creation of a genetic research program for individuals with PSP, CBS, and MSA. While there may be participant bias in enrollment, this early experience suggests that genetic factors in the pathogenesis of atypical parkinsonism may be greater than previously assumed.