Objective: To i) establish an expert consortium on PRKN/PINK1-linked Parkinson’s disease (PD), ii) improve our understanding of genotype-phenotype relationships and disease mechanisms, and iii) establish a biorepository based on 500 participants.

Background: Increasing evidence suggests different mechanisms to drive the pathology of PD, complicating the identification of biomarkers and treatment targets. To address this heterogeneity, efforts are being made to stratify PD into genetically defined subtypes. Mitochondrial dysfunction is the driving mechanism in PRKN/PINK1-associated PD. Elucidating the pathophysiology requires a large and ethnically diverse study population, detailed clinical data, and a comprehensive set of biomaterials – potentially resulting in a clinical trial-ready cohort.

Method: From previous monogenic team cohort efforts, we identified a group of PRKN/PINK1 experts and the corresponding study centers(1–3). All study centers will recruit affected and unaffected carriers of pathogenic variants in PRKN/PINK1 and matched idiopathic PD (iPD) patients, and healthy controls. To estimate recruitment numbers, we conducted an online survey. Using the PPMI dataset as template, we developed an eCRF and tracking system. Assessments include demographic and clinical data, (non-)motor scales, treatment, and imaging. Biomaterials (DNA, serum, plasma, RNA, urine, whole blood for PBMCs, and CSF) will be collected and preprocessed in a standardized fashion and stored in a central biorepository.

Results: We identified 13 study centers worldwide (4 Asian, 8 European, and 1 North American) to contribute ideas to our project and to enroll participants. Currently identified individuals include for PRKN/PINK1:  n=141/n=29 bi-allelic, n=83/n=14 mono-allelic affected carriers of pathogenic variants, and n=44/n=9 unaffected carriers of mono-allelic pathogenic variants. Each individual carrying a pathogenic variant will be matched with one individual with iPD and one healthy control person. Out of 13 centers, 9 have obtained IRB approval, and we successfully recruited the first two participants in February 2025.

Conclusion: Building on previous team science efforts, we have established a framework for the comprehensive study of PRKN/PINK1 PD, along with the generation of a large biorepository on PRKN/PINK1.

References: 1. Kasten M, Hartmann C, Hampf J, Schaake S, Westenberger A, Vollstedt E-J, et al. Genotype-Phenotype Relations for the Parkinson’s Disease Genes Parkin , PINK1 , DJ1: MDSGene Systematic Review. Mov Disord. 2018 May 11;33(5):730–41.
2. Vollstedt E-J, Kasten M, Klein C, MJFF Global Genetic Parkinson’s Disease Study Group. Using global team science to identify genetic parkinson’s disease worldwide. Ann Neurol. 2019 Aug;86(2):153–7.
3. Skrahina V, Gaber H, Vollstedt E, Förster TM, Usnich T, Curado F, et al. The Rostock International Parkinson’s Disease (ROPAD) Study: Protocol and Initial Findings. Mov Disord. 2020 Dec 14;mds.28416.

« Back to 2025 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/the-mjff-prkn-pink1-project/