Dr. Benjamin Delprat

University of Montpellier, France

 

In my lab, we are developing concomitantly two therapeutic strategies: a pharmacological approach and a gene therapy. To achieve these goals, we are working with suited animal models: two transgenic mouse lines and one zebrafish line. One mouse model and the zebrafish line are deficient for Wolframin, the protein responsible for Wolfram syndrome type 1. The other mouse model has been genetically engineered to mimic a human mutation, recapitulating sensorial deficits (vision and hearing loss) and diabetes. We are hoping to treat vision and hearing, as well as central neurodegeneration.

 

– Update –

 

* We have explored the impact of the absence of Wolframin or the presence of an abnormal protein in the neurons of our mouse models (neurons of the hippocampus and cortex) as well as in patients’ fibroblast (cells cultured from the skin). Our findings suggest considering the use of the same therapeutic targets in both cases, thus opening treatment perspectives for patients carrying a mutation leading to an abnormal protein (Wolfram-like syndrome).

 

* Using our zebrafish model of the disease, we have validated our gene therapy strategy. Based on these encouraging results, we are now investigating the outcomes of this approach in our mouse models.

Our gene therapy approach corrected the memory deficit and locomotor coordination alteration at least one month after the injection of the virus. In addition, the virus is efficiently transducing the affected brain structure such as cerebellum, hippocampus, or cortex and lasting in time.

We are now exploring vision and hearing loss of our preclinical models, following the injection of the virus.