Funded Studies
Objective/Rationale:
Recent studies have revealed that defects in a gene known as GBA1 are the most common genetic cause of Parkinson’s disease (PD). The GBA1 gene is known to play a role in fat metabolism, and this finding has led to a wide variety of models to explain how GBA1 gene defects cause PD. The goal of our work is to create similar GBA1 gene defects in a pre-clinical model.
Project Description:
In particular, we will test whether dopamine-secreting nerve cells in pre-clinical models with these gene defects degenerate, as is seen in humans with PD. We also plan to use these strains to begin to test models by which defects in the GBA1 gene cause PD, including the model that GBA1 gene defects interfere with the disposal of defective proteins and other cellular constituents that normally takes place within the cell.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
There are currently no preventative treatments for PD. Our work is aimed at an understanding of how defects in the GBA1 gene, the most common genetic form of PD, trigger the cascade of events that culminates in PD. This knowledge will prove crucial to the development of specific treatments for this disorder.
Anticipated Outcome:
We hope to learn whether our model will provide a good system in which to study the effects of GBA1 gene defects on PD, and to begin to define how these gene defects cause PD. If, at the completion of our studies, we have not yet defined how defects in GBA1 cause PD, we should be very well positioned to compete successfully for federal funding to complete these studies.
Progress Report
Recent studies have revealed that defects in a gene known as GBA1 are the most common genetic cause of Parkinson’s disease (PD). The GBA1 gene is known to play a role in fat metabolism, and this finding has led to a wide variety of models to explain how defects in the GBA1 gene cause PD. The goal of our work was to create similar GBA1 gene defects in a pre-clinical model.
Although we used a variety of genetic tools to create genetic defects in models of the GBA1 gene, we were unable to detect features of PD in these models. However, all of the strains we created likely retain some residual GBA1 gene activity. We have recently created a genetic strain that completely lacks GBA1 gene activity, and our future work will test whether this strain displays features of PD, and is thus suitable for experiments to test models by which defects in this gene cause PD.
November 2012
Researchers
-
Leo J. Pallanck, PhD