Molecular approaches for the treatment and prevention of Friedreich's ataxia.

Friedreich's ataxia (FRDA) is caused by an intronic guanine-adenine-adenine (GAA) trinucleotide expansion in the gene encoding frataxin (FXN). This triggers the transcriptional silencing of FXN and subsequent frataxin protein deficiency in affected cells, which accounts for the multisystemic symptoms of this condition. Current management strategies aim for symptomatic relief and no treatments can prevent disease onset or progression. Thus, research efforts have focused on targeting the molecular pathways that silence FXN and downstream pathological processes. However, progression of potential therapies into clinical use has been hindered by inconclusive clinical trials because of the small patient sample size associated with the low prevalence of this condition. Here, we discuss various molecular approaches and explore their therapeutic potential to alter the course of this progressive condition.