Friedreich’s ataxia: clinical features, pathogenesis and management

Abstract

Management of Freidreich's ataxia is currently focussed on symptomatic management, delivered by the multidisciplinary team. Phase II clinical trials in agents that address the abberrant silencing of the frataxin gene need to be translated into large placebo-controlled Phase III trials to help establish their therapeutic potential.

A Comprehensive Transcriptome Analysis Identifies FXN and BDNF as Novel Targets of miRNAs in Friedreich’s Ataxia Patients

“…Friedreich's ataxia (FRDA, FA) is an autosomal recessive neurodegenerative disease that affects about 15,000 people worldwide, making it the most common inherited ataxia [1][2][3][4]. The vast majority of FRDA patients are homozygous for expanded GAA trinucleotide repeats in the first intron of the frataxin (FXN) gene.…”

Molecular and Cellular Substrates for the Friedreich Ataxia. Significance of Contactin Expression and of Antioxidant Administration

“…In this study, rodent models of the inherited neurological disorder known as the Friedreich Ataxia (FA) [ 1 , 3 , 8 , 13 , 22 , 60 ] have been used to address the significance in the corresponding phenotype of the profiles of neuronal and glial cell lineages, with a specific concern on the underlying cell-type-specific molecular substrates. At the same time, the protective effects have been evaluated of specific treatments based on antioxidants/nutraceuticals administration, in particular of polyphenol derivation.…”

“…The Friedreich Ataxia (FA) is an autosomal neurodegenerative disorder, which affects the development of the long-range axonal trajectories, which grow along the spinal cord and include both sensory and spino-cerebellar afferents [ 1 , 2 , 3 ]. The corresponding tissue alteration affects sensory as well as spino-cerebellar functions [ 2 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ] and, as such, it results in an ataxic phenotype [ 9 , 14 , 15 , 16 ].…”

“…As for their derivation at the tissue level, the perikarya of most of the neurons affected by the Frataxin gene mutation map within the dorsal root ganglia as well as within the cerebellar dentate gyrus, which therefore represents the primary targets of the disorder [ 33 ]. At the cellular level, Frataxin gene mutation results in high sensitivity of the affected tissues to oxidative stress [ 7 , 12 , 34 ], which, in turn, is also relevant for devising potential therapeutic approaches, based on the administration of antioxidants components, demonstrated to be helpful also in other neurodegenerative disorders as shown for Idebenone, Mitochinone, Q10 coenzyme, vitamin E and for polyphenol components [ 1 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. The administration of such compounds attenuated the consequences of the disorder at the tissue level [ 11 , 37 ] thus exerting protective effects against the associated degeneration.…”

The magnificent quintet of trinucleotid repeat disorders: Spinal and bulbar muscular atrophy, Huntington’s disease, Friedreich ataxia, myotonic dystrophy, and fragile X syndrome

“…Friedreich ataksisinde GAA segmentinde tekrarlanma genellikle 600-900 arasında görülür. [22] Bu tekrarlanmayla birlikte FXN geni fraxin proteini yapımını baskılamaya balar. [21] Hastalı¤ın karakteristik bulguları anormal göz hareketleri (%90.5), skolyoz (%73.5), ayak deformiteleri (%58.8), üriner disfonksiyon (%42.8), kardiyak miyopati ve kardiyak hipertrofi (%40.3), azalmı görme keskinli¤i (%36.8); daha az olarak da depresyon (%14.1) ve diyabet (%7.1)'dir.…”