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Funded Studies

Resolving the Pathophysiology of Parkinson's Disease with GBA Mutations

Study Rationale:
Mutations in the GBA gene are the greatest genetic risk factor for developing Parkinson’s disease (PD). We will systematically examine pathophysiological pathways in PD patients with a GBA mutation (referred to as PD-GBA), compared to PD patients who do not have a GBA mutation and compared to controls in order to identify novel pathways and therapeutic targets.

We hypothesize that pathological pathways differ between PD and PD-GBA patients, which could potentially be responsible for the earlier onset of symptoms and increased cognitive challenges observed in PD-GBA patients.

Study Design:
We will carry out high-throughput, next-generation sequencing (RNAseq and proteomics) using a unique human brain tissue collection assembled via the Queen’s Square Brain Bank. This collection consists of tissues from five brain regions of 21 control, 21 PD and 21 PD-GBA patients, all age- and sex-matched. We will perform high-throughput analyses in these brain areas, which include areas primarily affected in PD (i.e., the substantia nigra) and areas that are less-well studied but in which significant pathology is observed.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
Identifying possible unique pathological pathways associated with PD-GBA could lead to novel therapeutic interventions. While pathology associated with nigrostriatal (dopamine) pathways is treated similarly in both PD-GBA and PD patients, we believe that delineating, and eventually targeting, other pathways should provide hope for treatment of PD-GBA.

Next Steps for Development:
If we are able to identify novel pathophysiological pathways in PD-GBA patients, then these might be targets for currently existing therapies. For instance, if neuroinflammatory pathways are differentially affected in PD-GBA, then currently available neuroinflammatory drugs could be re-positioned to target these pathways in PD-GBA patients.


  • Anthony H. Futerman, PhD

    Rehovot Israel

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