Emerging therapies in Friedreich's Ataxia

Friedreich's ataxia (FRDA) is a progressive, neurodegenerative disease that results in gait and limb ataxia, diabetes, cardiac hypertrophy, and scoliosis. At the cellular level, FRDA results in the deficiency of frataxin, a mitochondrial protein that plays a vital role in iron homeostasis and amelioration of oxidative stress. No cure currently exists for FRDA, but exciting therapeutic developments which target different parts of the pathological cascade are on the horizon.

Areas covered include past and emerging therapies for FRDA, including antioxidants and mitochondrial-related agents, nuclear factor erythroid-derived 2-related factor 2 (Nrf2) activators, deuterated polyunsaturated fatty acids, iron chelators, histone deacetylase (HDAC) inhibitors, trans-activator of transcription (TAT)-frataxin, interferon gamma (IFNγ), erythropoietin, resveratrol, gene therapy, and anti-sense oligonucleotides (ASOs), among others.

While drug discovery has been challenging, new and exciting prospective treatments for FRDA are currently on the horizon, including pharmaceutical agents and gene therapy. Agents that enhance mitochondrial function, such as Nrf2 activators, dPUFAs and catalytic antioxidants, as well as novel methods of frataxin augmentation and genetic modulation will hopefully provide treatment for this devastating disease.