Objective:

Can the Global Parkinson’s Genetics Program (GP2, http://gp2.org/) leverage its rich data and connectivity to address the growing issue of identifying individuals that can participate in precision medicine initiatives, and facilitate the development of an effective recruitment protocol?

Background: GP2 aims to integrate clinico-genetic data from >200,000 participants and is a global research community dedicated to rapidly addressing emerging research needs in Parkinson’s disease (PD). The lack of disease-modifying treatments and the difficulty of recruiting participants for precision medicine initiatives are challenges for many biotech/pharmaceutical companies. As it has been estimated that the probability of success for drug mechanisms with genetic support is 2.6 times greater than those without1, we aim to investigate whether GP2 can help facilitate the development of an effective recruitment protocol.

Method: We analyzed whole genome sequence (WGS), raw genotype, and clinical data in the latest data releases in GP2 (v8 and 9), with genetic data for ~35,000 PD patients (6,113 WGS and 28,965 genotyped). To identify eligible participants, the main inclusion criteria were variants of interest in LRRK2 and GBA1 (mutations and established risk variants) and a mean time from diagnosis to age at last visit of ≤ 5 or 7 years in order to identify cohorts with at least 10 participants meeting these criteria, prioritizing those with ongoing recruitment.

Results: We identified 1,283 participants (3.7%) with LRRK2 variants with detailed clinical data collected for 647 of these (61% non-PPMI). Approximately 215 (16.8%) had a mean time from diagnosis to present ≤5 years and 260 (40.2%) ≤7 years. A total of 2,872 GBA1 carriers (8.2%) were identified and 914 (82% non-PPMI) had extended clinical data. Over 340 (12.0%) of those had a mean time from diagnosis to present ≤ 5 years and 413 (45.2%)  ≤7 years, meeting a primary inclusion criterion for many clinical trials. For LRRK2, 12 cohorts with ongoing recruitment had ≥10 carriers vs 13 cohorts for GBA1.

Conclusion: Here we present a guide to assist with concepts of trial recruitment resources, leveraging existing data and collaborations to aid the unmet needs in PD research. Utilizing the data and network within GP2, we anticipate this to be a valuable resource for future precision medicine projects with >110,000 PD patients expected to be genotyped.

References: Minikel, E. V., Painter, J. L., Dong, C. C., & Nelson, M. R. (2024). Refining the impact of genetic evidence on clinical success. Nature, 629(8012), 624–629. https://doi.org/10.1038/s41586-024-07316-0

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MDS Abstracts - https://www.mdsabstracts.org/abstract/utilizing-the-global-parkinsons-genetics-program-gp2-to-develop-a-precision-medicine-recruitment-protocol/