Therapy for Friedreich's ataxia
FRDA is a rare autosomal recessive neurological disease that leads to an inability to walk and perform many activities. The disease is caused by mutations in the frataxin gene and some patients also present with cardiomyopathy, visual and auditory loss or kyphoscoliosis. The rarity of the disease, and the fact that clinicians specialising in FRDA are dispersed, hinder the provision of healthcare to patients. To address this and improve current knowledge on the disease, the EU-funded EFACTS (European Friedreich's ataxia consortium for translational studies) brought together all European FRDA experts who had made significant contributions in the FRDA field. The rationale was to defragment FRDA research and integrate European scientific efforts towards novel therapies. Apart from progressing our understanding on FRDA, the consortium aimed to improve the clinical assessment and diagnosis of FRDA patients. In addition, it set out to implement the first pan-European FRDA database registry of nearly 600 patients, linked to bio banks of patient material. Researchers delineated frataxin’s essential role in human iron-sulphur cluster (ISC) biogenesis and identified the interactions in the mitochondrial matrix. Defective ISC synthesis was recognised as the primary cause leading to cellular dysfunction and death due to frataxin deficiency. The identification of novel pathways implicated in FRDA pathogenesis indicated new potential therapeutic targets. Equally important was the generation of cellular and animal models of the disease that would facilitate future studies. From a clinical perspective, the follow-up of patients provided important data on disease progression and identified robust progression markers and performance tests. Clinicians also updated existing evidence on FRDA healthcare and generated recommendations for provision of improved clinical care. Importantly, the EFACTS network of clinical sites provided an essential infrastructure for future clinical trials in Europe, combining medical expertise and patient availability. Finally, the consortium made considerable progress towards the identification of novel therapeutics and their clinical development. In this context, two clinical trials commenced based on EFACTS-generated data. Project dissemination activities improved awareness of FRDA and made an impact on the quality of life of patients and families. The consortium envisions its efforts on diagnosis, disease management and expert care provision will improve the clinical outcome of FRDA sufferers.
Keywords
Friedreich ataxia, frataxin, , iron-sulphur cluster, pathway, therapeutic
