Skip to main content
Funded Studies

From Genetic Risk Toward Genetic Prognosis

The progression and prognosis of Parkinson’s disease (PD) varies considerably between individual patients — ranging from a manageable, functional decline to an aggressive course. This variation is a major source of noise and inefficiency in clinical drug trials. To overcome this roadblock, markers that predict prognosis are needed — for improving trial design as well as for a personalized clinical care.

Project Description:             
Variants in a known PD risk gene will be systematically identified through resequencing of the locus in the ~ 400 PD patients with available DNA enrolled and longitudinally followed in the DATATOP (Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism) study. Statistical analyses will be performed to determine whether these variants predict disease progression.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:                     
Prognostic markers will enable recruiting trial populations with a more homogeneous disease course thereby increasing power, lowering sample sizes, saving costs and facilitating mechanism-directed therapies.

Anticipated Outcome:          
Consistent with our preliminary studies, DATATOP participants carrying these gene variants will have a more rapid disease progression.

Final Outcome

The effect of gene mutations on cognitive and motor outcomes were evaluated in DATATOP (current award) and additional cohorts (additional MJFF support) comprising 2,304 patients with PD using sequencing (in 1,921) or genotyping (in 383). Patients carrying a mutation had a 63% increased risk of developing dementia over ten years compared to patients free of a mutation. They had a 46% increased risk of rapid motor disease progression.

Much progress has been made in delineating genome variation associated with susceptibility for developing PD, but little is known about the genetic architecture controlling disease progression. With this study we propose to shift the paradigm from genetic risk to genetic prognosis. Progression genes should facilitate patient stratification and recruiting trial populations with a more homogeneous disease course thereby increasing power, lowering costs, and facilitating mechanism-directed therapies.


  • Clemens Scherzer, MD

    Boston, MA United States

  • Brendon P. Boot, MBBS

    Boston, MA United States

Discover More Grants

Search by Related Keywords

Within the Same Program

Within the Same Funding Year

We use cookies to ensure that you get the best experience. By continuing to use this website, you indicate that you have read our Terms of Service and Privacy Policy.