EXCITING GENETIC DISCOVERIES FUNDED BY APDA

May 6, 2021

In an exciting new study, researchers at the APDA Center for Advanced Research at Brigham and Women’s Hospital studied the genetic changes that increase the rate of progression of Parkinson’s disease (PD).

Currently, there are many genes that are associated with an increased risk of developing PD. But once a person has been given a diagnosis of PD, doctors can predict very little about how the disease will progress. This uncertainty is frustrating for people with PD who are understandably very concerned about what direction their disease might take.

The new study, led by Dr. Clemens Scherzer, Director of the APDA Center for Advanced Research at Brigham and Women’s Hospital and member of the APDA Scientific Advisory Board, looked at genetic risk factors associated not with developing PD, but with rate of progression of PD. A massive effort screened genetic variants in thousands of PD patients and correlated the variants with progression of cognitive decline as captured by cognitive testing performed over time.

Researchers found five genetic locations associated with a more rapid progression of PD and developed a risk score for predicting development of dementia in PD. Three of the genes discovered had not previously been linked to PD: RIMS2 is a gene involved in synaptic vesicle docking; TMEM108, is implicated in synaptic spine formation and cognition; and WWOX has very recently been associated with increased risk of Alzheimer’s disease. Two of the genes are already well connected to PD and dementia: GBA and APOE4. Interestingly, RIMS2 had a more than 2.5-times stronger effect on cognition than the GBA and APOE4 genes which have already been well studied.

Why is this research important? This research suggests that the risk factors for PD progression can be very different than the risk factors for developing the disease to begin with. It also suggests that drug development should focus not just on the genetic drivers that start the PD process, but on those that drive progression as well.

APDA is thrilled to have been a funding partner in this groundbreaking work. To help us continue to support vital PD research, please consider donating to APDA.

Paper cited: Liu G, et al. “Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson’s disease” Nature Genetics DOI: 10.1038/s41588-021-00847-6