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Funded Studies

Identifying Genes that Enhance the Activity of Glucocerebrosidase

Study Rationale: Parkinson’s disease (PD) causes uncontrollable trembling, progressive rigidity of muscles and an inability to walk. We do not yet understand why certain people are more prone than others to develop the disease or why symptoms and progression differ greatly between individuals. Studies have shown that the activity of a protein called β-glucocerebrosidase is impaired in many people with PD, and mutations in this protein are an important risk factor for the disease — although not all people with a mutation will develop PD. In our laboratory, we wish to discover genes that regulate and potentially improve the function of glucocerebrosidase. 

Hypothesis: The goal of our study is to better understand why certain people with a malfunctioning glucocerebrosidase develop PD, while others do not.  

Study Design: We tested over 1,600 genes for their ability to improve the functioning of glucocerebrosidase. Our next step will be to further assess the ability of candidate genes to enhance the activity of this protein in nerve cells derived from individuals with PD. This testing will involve the use of specialized chemicals that can reliably measure the activity of glucocerebrosidase in these cells. 

Impact on Diagnosis/Treatment of Parkinson’s disease: Our findings could help explain why certain people are more likely to develop PD than others. In addition, a better understanding of the mechanisms involved in the proper functioning of glucocerebrosidase might enable the development of new treatment strategies tailored to people with PD based on their genetic risk factors.  

Next Steps for Development: Further testing of the genes and mechanisms identified in our study in more complex preclinical models will be the next step towards the development of treatment approaches improving the functioning of glucocerebrosidase. 


  • Adriano Aguzzie, MD, DVM, FRCP

    Zurich Switzerland

  • David Vocadlo, PhD

    Burnaby BC Canada

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