Project goal: Develop a gene therapy1 to prevent ataxia and neurodegeneration linked to a dysfunction of the PEX16 gene.
The PEX genes are required for the formation and function of peroxisomes, which are small but important compartments of the cell. These little organelles have several big roles, including regulating the production and breakdown of fats (lipids). Some of these lipids are essential components of myelin, a fatty layer that surrounds and protects nerve cells and ensures proper nerve function.
Mutations in PEX genes cause problems in peroxisome formation and hence lipid metabolism. Our project focuses on peroxisome disorders regulated by the PEX16 gene. Patients who have a problem with the PEX16 gene present symptoms mainly related to the brain, characterized by ataxia and progressive spasticity. There is no cure, nor are there any models useful to study the brain disease and develop a therapy.
To address this need, we will:
- Develop the first Pex16-deficient mouse model related to the clinical disease.
- Study how well the mouse mimics the disease, i.e. shows symptoms like those of patients. To do this, we will perform neurological tests on the mouse and examine its brain and lipids. If the mouse mimics the disease well, it can be used to develop a therapy.
- We will test whether the mouse’s symptoms can be prevented or improved by gene therapy using the human PEX16 gene.
If successful, this would be a first (preclinical) step towards the development of a PEX16 gene therapy that could help alleviate this disease and radically improve patients’ quality of life.
In addition, this study would help us to increase our knowledge of how peroxisomes function, their role in the brain and could encourage other researchers to investigate the matter. Our study involves renowned, multidisciplinary researchers from different countries, and our team has already successfully completed a similar study for another gene.
1 What is gene therapy? Gene therapy makes it possible to repair defective genes in cells or add missing genes to treat various diseases.