Baylor Study Links Mutations in Lysosomal Genes to Parkinson’s Disease

Baylor Study Links Mutations in Lysosomal Genes to Parkinson’s Disease

A  new study by researchers at Houston’s Baylor College of Medicine has linked a group of genes associated with lysosomal storage disorders, such as Gaucher disease, to the onset and progression of Parkinson’s disease.

The study, “Excessive burden of lysosomal storage disorder gene variants in Parkinson’s disease,” appeared in the journal Brain.

Parkinson’s has a significant genetic component, with more than 30 genes contributing to it — especially mutations in the glucocerebrosidase gene (GBA), the cause of Gaucher.

“Individuals with Gaucher disease can have family members with Parkinson’s disease,” Dr. Laurie Robak said in a Baylor press release. “People who carry one defective copy of the GBA gene have a 5- to 8-fold increase in the risk of having Parkinson’s disease later in life.”

As Gaucher is a lysosomal storage disorder (LSD), researchers hypothesized that other LSD genes could be associated with susceptibility to Parkinson’s. The lysosomes are also referred to as the waste clearing system of a cell.

That led Baylor researchers to use data from the largest Parkinson’s whole exome sequencing dataset — which contains information about mutations — in order to determine whether an overlap of gene mutations wee responsible for development of both LSDs and Parkinson’s.

Results from the study, obtained from two independent cohorts, revealed a significant number of LSD gene variants linked to Parkinson’s development. Even when GBA was excluded from the data set, the association between LSD gene variants and Parkinson’s was very strong.

When looking at specific genes that were correlated with a high risk for Parkinson’s, the known genes GBA and SMPD1 were confirmed. Researchers also implicated CTSD, SLC17A5 and ASAH1 as new Parkinson’s disease risk factor genes.

In this group of patients, 56 percent had at least one LSD gene variant and 21 percent had more than one LSD gene variant. Authors note that having multiple LSD gene variants could act jointly to increase lysosome damage and make patients more susceptible to Parkinson’s.

“Although more research remains to be done, these data suggest the interesting possibility that damage to the lysosome might be at the core of Parkinson’s disease,” said Dr. Joshua Shulman, assistant professor at Baylor. “It might be possible that Parkinson’s disease and lysosomal storage disorders have similar fundamental biological mechanisms.”

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