Ataxia Telangiectasia: International Clinical Trial Readiness for Phase 3 Trials Correcting Mitochondrial Dysfunction

A-T is a rare genetic with an incidence of approximately 3 in one million births. Patients with A-T are wheelchair bound by the end of the first decade and life expectancy is ~25years, with neurodegenerative cerebellar ataxia, lung disease from immune deficiency, and cancer, accounting for a high mortality and disease burden. Recent focus has been on the role of mitochondria in terms of creating symptoms in A-T patients, and as a potential treatment target. Mitochondria are energy packets inside human cells that are essential for human life. Australian investigators have published detailed causes of mitochondrial dysfunction in A-T cells, that are corrected with supplementation of a compound called triheptanoin (C7) which is an oil used to treat genetic disorders of fat metabolism. This group has also completed a successful clinical trial for the use of C7 in A-T patients, with statically significant and clinically significant improvements across the clinical trial assessment outcomes. Dutch colleagues have completed a successful trial of nicotinamide riboside (NR) supplementation in A-T patients. NR serves to improve mitochondrial function via different mechanisms to C7. The Australian group have demonstrated that combining C7 and NR improved A-T cell function in the laboratory. The A-T International community is highly collegial and supported by patient run support groups. The community would like to explore testing the combination of C7 and NR in a multi-national phase 3 clinical trial. This networking grant will assist greatly in the preliminary planning and organisation for the trial.