Study Rationale:
Multiple system atrophy (MSA) and Parkinson’s disease present with similar clinical symptoms, especially at early stages. Though both involve the abnormal accumulation of α-synuclein protein, MSA progresses more rapidly than PD and does not respond well to dopaminergic therapy, indicating unique biological dysregulation for each disease. Uncovering these differences will provide important insights for therapeutic development for both disorders. Changes in the levels of proteins and other molecules in biological fluids (biomarkers) during the disease course in MSA and PD can serve to reveal these differences.
Hypothesis:
Our goal is to identify biological markers that distinguish MSA from PD and that change with disease progression for both disorders.
Study Design:
Since MSA is a rare disorder, we formed a collaborative consortium of 5 major clinical centers in the U.S. and Europe that will pool together our MSA patient populations to obtain enough samples for consistent measurements. Each site will collect detailed clinical data and biological specimens, including blood and cerebrospinal fluid, in a standardize way to be stored in a centralized location. From these fluids, we will measure the levels of neurological disease-related proteins, metabolites, and lipids as potential biomarkers.
Impact on Diagnosis/Treatment of Parkinson’s disease:
Identifying biomarkers that distinguish MSA from PD and track disease progression will instruct efforts to develop therapeutics, select the appropriate populations for clinical trials, and allow the assessment of whether potential therapeutics are effective.
Next Steps for Development:
The information learned from this study will be used to select targets for basic science studies to further understand which biological processes are dysregulated in MSA and PD. Importantly, once the targets are validated in larger patient cohorts, they can be used to track the disease progression and for monitoring the efficacy of new therapeutics.