Friedreich’s Ataxia is caused by a deficiency in frataxin resulting in an increase in oxidative stress. ‘Oxidative stress’ occurs when there is an imbalance between the production of harmful free radicals and the antioxidants that protect the body against the potential damage they cause. A protein called ‘nuclear factor erythroid 2-related factor 2’, or ‘Nrf2’ for short, helps to control the amount of antioxidants in the body. It has been shown that frataxin deficiency reduces the expression of Nrf2 in mouse models of the disease.
Although symptoms of FA normally don’t begin until the second decade of life, evidence suggests that problems may begin during the process of ‘foetal neurogenesis’, which is when the brain and spinal cord of a developing baby is formed. A recent study investigated the expression of Nrf2 in neural stem cells taken from embryos belonging to mice with FA to see what effect this would have on the development of the brain and spinal cord.
The researchers found that the level of Nrf2 in embryos taken from the mice with FA was reduced compared to controls, and confirmed that this affected the development of the brain and spinal cord. They also discovered that increasing the amount and activity of Nrf2 using the drugs Sulforaphane (SFN) and EPI-743 re-established normal development. The full article is available here.
SFN and EPI-743 are gaining positive attention as potential candidates for the treatment of neurodegenerative disorders including FA. In August last year Ataxia UK reported on a phase 2 clinical trial testing EPI-743 in patients with FA, which showed promising results.