Friedreich’s ataxia is an inherited, debilitating, and degenerative neuromuscular disorder that is normally diagnosed during adolescence and can lead to early death. Patients with FA experience progressive loss of coordination, muscle weakness, and fatigue, which commonly progresses to motor incapacitation and wheelchair reliance1. FA patients may also experience visual impairment, hearing loss, diabetes, and cardiomyopathy. Childhood-onset FA can occur as early as age five, is more common than later-onset FA, and typically involves more rapid disease progression. The majority of FA patients have disease onset by approximately 13 to 15 years of age, and thereafter have a mean duration until wheelchair use of 10 to 15 years. The median age of death is in the mid-30s2,3,4.
There are no currently approved therapies for the treatment of FA. Patients are usually given guidelines around certain lifestyle habits. They are recommended to follow a diet that is low in iron and encouraged to take vitamins and supplements5. Because omaveloxolone targets molecular pathways involved in impaired bioenergetics and chronic inflammation and penetrates the blood-brain barrier, we believe that the drug could provide a benefit to FA patients.
FA is an ultra-orphan disease. There are an estimated 22,000 people globally with FA, including an estimated 6,000 to 7,000 in the United States and approximately 9,500 in the European Union6.
Mechanism of Action
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- Vankan et al. Prevalence gradients of Friedreich’s Ataxia and R1b haplotype in Europe co-localize, suggesting a common Palaeolithic origin in the Franco-Cantabrian ice age refuge. J Neurochem. 2013 Aug;126 Suppl 1:11-20.
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- Shan Y, Schoenfeld RA, Hayashi G, et al. Frataxin deficiency leads to defects in expression of antioxidants and Nrf2 expression in dorsal root ganglia of the Friedreich’s ataxia YG8R mouse model. Antioxid Redox Signal 2013; 19:1481-93.
- D’Oria V, Petrini S, Travaglini L, et al. Frataxin deficiency leads to reduced expression and impaired translocation of NF-E2-Related Factor (Nrf2) in cultured motor neurons. Int J Mol Sci 2013; 14:7853-65.
- Paupe et al. Impaired nuclear Nrf2 translocation undermines the oxidative stress response in Friedreich ataxia. PLoS One 2009; 4:4253-64.
- Holmström KM, Baird L, Zhang Y, et al. Nrf2 impacts cellular bioenergetics by controlling substrate availability for mitochondrial respiration. Biol Open 2013; 0:1-10.