In an exciting new study, researchers at the APDA-funded Center studied the relationship between the activity of the glucocerebrosidase (GBA) enzyme and the risk of Parkinson’s disease (PD). This insight may help shed light on possible future treatments.
The glucocerebrosidase (GBA) enzyme, encoded by the GBA gene, is a protein used by the body to break down cellular products. Having two abnormal GBA genes causes Gaucher’s disease, which is characterized by the buildup of these cellular products resulting in fatigue, bone pain, easy bleeding and an enlarged spleen and liver. When a person inherits only one abnormal gene, he or she does not develop Gaucher’s disease, but does incur a small increased risk of PD.
Current research has established a correlation between particular GBA mutations and particular PD characteristics. For example, there are particular GBA mutations associated with cognitive decline in PD. In addition, certain GBA mutations are associated with an overall higher risk of developing PD than other mutations. The reasons that these mutations affect PD risk in different ways is poorly understood.
In newly-published work from the APDA Center for Advanced Research at Brigham and Women’s Hospital, the research group led by Dr. Clemens Scherzer, Director of the Center and member of APDA’s Scientific Advisory Board, delved into why different GBA mutations have different effects on PD. They demonstrated that different GBA mutations affect the enzymatic activity of the GBA protein differently. That means, that different mutations change the ability of the GBA protein to function to different degrees. GBA mutations that are associated with a higher risk of PD or more severe PD symptoms, had lower enzymatic activity than less severe mutations.
The study was particularly powerful, because the samples used were highly clinically characterized, that is, detailed clinical information was available on each person with PD who donated their bio-samples to the study. This allowed the study to correlate the enzymatic activity of GBA with PD progression. The study demonstrated that GBA activity decreased as PD progressed and that severe GBA mutations showed the steepest decline over time.
This work suggests that GBA mutations contribute to increased PD risk by affecting the enzymatic activity of GBA. This further suggests that improving GBA enzymatic activity could be a beneficial strategy for treating PD.
People with PD may be curious about whether they carry a GBA mutation. Read this article to learn more about the topic of genetic testing in PD.
APDA is proud to provide crucial support to the Center to enable and accelerate such ground-breaking work and salutes Dr. Scherzer and his team for their achievement.