Study Rationale: Parkinson’s disease (PD) is an umbrella term that encompasses a highly heterogeneous domain of clinical manifestations, which makes the development of effective therapeutic strategies and the prediction of clinical outcomes extremely challenging. Our work aims to characterize the PD subtypes previously proposed by the scientific community using data from the Parkinson’s Progression Marker Initiative (PPMI). We will attempt to identify immunologic markers that could drive the different disease outcomes for each subtype, explore the potential of genetic data to improve the current subtyping strategies and provide insights on novel biomarkers and therapeutic targets.
Hypothesis: We hypothesize that genetic data related to the immune system holds valuable information regarding the onset and progression of the different PD subtypes, which could help identify causes of the disease, assist the diagnosis and accelerate the development of more appropriate therapies for each subtype.
Study Design: We will begin by classifying individuals from the PPMI on the different clinical subtypes previously proposed by three different studies. We will conduct a full characterization of these groups based on the available genetic data, focusing on the immune system. From these characterizations, we will extract potential biomarkers associated with the different clinical features observed in each subtype, including disease progression and severity. Finally, we will explore whether these biomarkers can be successfully used for the prediction of disease features on an independent dataset, available from the Parkinson’s Disease Biomarkers Program.
Impact on Diagnosis/Treatment of Parkinson’s disease: By successfully characterizing the clinical PD subtypes, we can gain insight into the different mechanisms involved in PD onset and progression in each subtype, providing novel approaches to therapeutic targets and strategies for the development of more efficient, subtype-directed clinical trials.
Next Steps for Development: We will translate the findings into studies on repurposing drug candidates, which could help on the development of novel subtype-directed clinical trials, and we will engage with the community to develop feasible ways of using the biomarkers and subtyping strategies for counseling and management of people with PD.