SUI GENERIS

Friedreich’s Ataxia is an autosomal recessively inherited, slowly-progressing disorder which is caused by the GAA trinucleotide repeat expansion in the first intron of the frataxin (FXN) gene. The transcriptional suppression of FXN results in a decrease in the production of the mitochondrial protein frataxin. There is a strong link between the number of GAA repeats and the onset of the disease. Several gene therapy studies have been carried about FA, to restore the frataxin deficiencies in the central nervous system, specifically in dorsal root ganglia, proprioceptive neurons, and motor neurons using frataxin-expression vectors. Here, we are aiming to deliver the human FXN gene into AAV with novel PHP.eB capsid, pAAV-CAG-GFP transfer vector in order to increase the frataxin levels in CNS, more specifically, the proprioceptive cells, and motor neurons using the conditional mouse model YG8sR (Fxntm1MknTg(FXN)YG8Pook/2J ) with complete frataxin deletion in both alleles. Multiple tests and analysis will be performed before and after transfection on the YG8sR conditional mouse model and the C57BL/6J wild-type mice as our control group at both pre-symptomatic and post-symptomatic stages. After comparing the test results of both mice models, we expect an increase in the frataxin levels and a rapid rescue and restoration of the sensory neuropathy, thereby introducing a gene therapy with the optimized capsid vectors. Delivering frataxin expressing pAAV-CAG-GFP intravenously and intracerebrally into mice is expected to increase the frataxin translation activity in the proprioceptive neurons, motor neurons in the dorsal root ganglia of patients with FA.