Developing therapies for Parkinson's disease

Abstract

Parkinson's disease is one of the most common neurological disorders and its prevalence more than doubled between 1990 and 2016 to over 6 million patients worldwide. This increase cannot be solely attributed to population ageing. The relatively high contribution of Parkinson's disease to the global burden of neurological diseases reflects its progressive, debilitating nature. In recognition of the importance of and need for large-scale data collection efforts to enable meaningful progress in the development of new therapies to treat this disease, the Accelerating Medicines Partnership for Parkinson's Disease (AMP-PD) initiative was established in 2018. The project is now entering a second ambitious phase. AMP-PD was built on the public–private AMP model to accelerate drug development in Parkinson's disease by creating a platform for sharing data, across multiple studies, with the broader scientific community and providing the expertise and support needed to establish diagnostic and prognostic biomarkers. The initiative is a collaboration between multiple agencies from government (National Institutes of Health [NIH] National Institute of Neurological Disorders and Stroke [NINDS], National Institute on Aging [NIA], the US Food and Drug Administration [FDA]), the non-profit sector (The Michael J Fox Foundation for Parkinson's Research [MJFF] and the Aligning Science Across Parkinson's [ASAP] Initiative), and the pharmaceutical industry (Bristol-Myers Squibb, GSK, Pfizer, Sanofi, and Verily). It is managed through the Foundation for the NIH. The first phase of AMP-PD has accumulated biosamples (both DNA for whole genome-sequencing and RNA) and longitudinal clinical data that are collected under comparable protocols and using common data elements from four MJFF-supported or NINDS-supported cohorts: BioFIND, Harvard Biomarkers Study, the Parkinson's Disease Biomarkers Program, and the Parkinson's Progression Markers Initiative. Data from a further three cohorts will be added by the end of 2020: the NIH Intramural Research Program Lewy Body Dementia Case-Control Cohort, the MJFF-sponsored LRRK2 Cohort Consortium, and the cohort from the NINDS-supported Efficacy of Isradipine in Early Parkinson Disease, Phase 3 (STEADY-PD3) trial. Combined, these seven cohorts will provide intensive biological and clinical data on more than 10 000 individuals. By the end of 2021, the repository will also include unbiased and targeted proteomics on over 1400 individuals. The data being accrued as part of these collaborations represent the most intensive molecular characterisation of individuals with Parkinson's disease. The second phase of the AMP-PD project will also include collaboration with the Global Parkinson's Genetics Program (GP2) to substantially increase the number of samples available. GP2 is a resource of the ASAP initiative and aims to collect and genotype samples from more than 150 000 individuals globally over the next 5 years. Two features of the data collection process are particularly notable. Firstly, the project will recruit participants from Africa, Asia, Europe, and the American continent, offering the opportunity to explore the genetic basis of Parkinson's disease across diverse populations that have traditionally been underrepresented in research. Secondly, recruitment will include individuals with rare familial forms of Parkinson's disease and utilise intensive gene discovery techniques to identify novel disease causing mutations. A feature of AMP-PD is commitment to collaboration and to open science. Andrew Singleton, Chief of the Laboratory of Neurogenetics at NIH and a lead investigator of GP2, describes these efforts as “an attempt to democratise science”. Given the breadth of the data already in AMP-PD and plans to further expand, a major focus of the project is to grant the broader scientific community access to these data by harmonising the data and making access and interpretation as easy as possible. Given the complexity of the data being collected, this in itself is no easy task. Nonetheless, the extensive clinical, genomic, and transcriptomic and related data available through the AMP-PD and GP-2 collaborations will likely remain the largest and most intensively characterised cohorts of people with Parkinson's disease. Enabling and expanding access to these data maximises the probability that their full potential will be realised. The scope of AMP-PD is ambitious, and the resources being devoted across this collaboration and the commitment of the people and organisations involved provide confidence that they will identify and validate biomarkers for Parkinson's disease. In turn, this offers hope for the development of therapies to reduce or eliminate the large burden that Parkinson's disease places on patients, their families, and on society.