Postdoctoral Research Scientist
Friedreich’s ataxia (FRDA) is the most common inherited recessive ataxia affecting children and young adults and is caused by a trinucleotide (GAA) repeat expansion in intron 1 of the frataxin gene (FXN). This expansion results in reduced levels of the mitochondrial protein frataxin (FXN) leading to increased susceptibility to oxidative stress and premature death of a subset of cells in the spinal cord and cerebellum. In FRDA, the GAA trinucleotide repeat expansion induces a repressive heterochromatin environment at the FXN locus resulting in expression of only ~10% of normal FXN expression levels. It is likely that increasing FXN protein levels in patients to 50% of wild-type (ie: to the level present in asymptomatic carriers) will be sufficient to arrest the pathological process. Increasing FXN levels is therefore key to treating the disease and is the focus of my current project.
The Wade-Martins laboratory has previously identified novel therapeutic targets and small molecule therapies which are able to increase FXN protein levels as a potential therapy. In this project I will test a lead series of compounds for biological efficacy in expression models and patient cell lines, including patient-derived induced pluripotent stem cell (iPSC)-derived neurons.