Evaluation of oligonucleotides for therapy of Friedreich ataxia

The aim of this project is firstly to characterise a novel transgenic mouse model of the multi-system autosomal inherited genetic disorder, Friedreich ataxia (FRDA). This mouse model, designated YG8LR, contains the human frataxin transgene together with an inserted 410 GAA repeat expansion mutation.

Our studies aim to characterise the FRDA mouse model at molecular, biochemical, histopathological and behavioural levels. Once characterised, the FRDA mouse model will then be used in preclinical studies to investigate the potential of specific frataxin oligonucleotides generated by Translate Bio to stabilize frataxin mRNA and hence increase frataxin expression.

The generation and characterisation of a mouse model for Friedreich ataxia will be a most useful tool that will be deposited in the Jackson Laboratory for distribution to Friedreich ataxia research investigators throughout the world.

The identification of oligonucleotides that have the ability to increase frataxin expression in a FRDA mouse model will provide important evidence for potential future clinical trials of Friedreich ataxia. This is a lethal devastating genetic disorder for which there is currently no effective therapy. Therefore, successful preclinical and clinical trials will have a major impact on the wellbeing of individuals who suffer with this disease. Furthermore, the technique of oligonucleotide therapy may have impact upon similar therapeutic strategies for other diseases caused by protein deficiency.