Study Rationale:
Predicting the prognosis of Parkinson’s disease (PD) for a patient is currently not possible. Genetic predictors of prognosis would help inform clinical trial design and, possibly, patient care.
Hypothesis:
We hypothesize that genetic variants in the glucocerebrosidase (GBA) and the alpha-synuclein (SNCA) genes are clinically relevant, powerful predictors of prognosis in sporadic PD.
Study Design:
Sequence variants in the GBA and SNCA genes will be analyzed using highly multiplexed, next-generation sequencing of 785 patients with PD enrolled in three longitudinal studies. Analysis will be performed for each study separately and across the studies in this international consortium.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Prognosis predictors will improve trial design and precision care for patients with PD. They can enable recruiting of trial populations with a more homogeneous disease course thereby increasing power, lowering sample sizes, saving costs and facilitating mechanism-directed therapies.
Next Steps for Development:
Confirmed genetic prognosis predictors will be used to shape future clinical trials for mechanism-directed therapies.