150 years of Friedreich Ataxia: From its discovery to therapy

摘要

In 1863, Nikolaus Friedreich (1825-1882), a German pathologist from Heidelberg, described a new spinal disease for the first time (Friedreich 1863a,b,c). However, it was only in 1876 that he had articulated the hereditary nature of the disorder (Koeppen 2013). It took a staggering 120 years to discover the genetic defect underlying Friedreich Ataxia (FRDA) (Campuzano et al. 1996). The identification of mutations in the gene encoding frataxin (FXN) initiated the rapid growth of a scientific field in which FRDA became a model disorder. Frataxin has been found to locate to mitochondria, control mitochondrial iron homoeostasis and, if deficient, lead to oxidative stress. Genetically, it is a recessively inherited disorder caused by an expansion mutation of GAA repeats in the first intron within the FXN gene, leading to a largely reduced expression of the frataxin protein.