Friedreich ataxia is the most frequent hereditary ataxia, with an estimated prevalence of 3-4 cases per 100,000 individuals. This autosomal-recessive neurodegenerative disease is characterized by progressive gait and limb ataxia, dysarthria, lower-limb areflexia, decreased vibration sense, muscular weakness in the legs, and a positive extensor plantar response. Non-neurological signs include hypertrophic cardiomyopathy and diabetes mellitus. Symptom onset typically occurs around puberty, and life expectancy is 40-50 years. Friedreich ataxia is usually caused by a large GAA-triplet-repeat expansion within the first intron of the frataxin (FXN) gene. FXN mutations cause deficiencies of the iron-sulfur cluster-containing subunits of the mitochondrial electron transport complexes I, II, and III, and of the iron-sulfur protein aconitase. Mitochondrial dysfunction has been addressed in several open-label, non-placebo-controlled trials, which indicated that treatment with idebenone might ameliorate hypertrophic cardiomyopathy; a well-designed phase II trial suggested concentration-dependent functional improvements in non-wheelchair-bound children and adolescents. Other current experimental approaches address iron-mediated toxicity, or aim to increase FXN expression through the use of erythropoietin and histone deacetylase inhibitors. This Review provides guidelines, from a European perspective, for the diagnosis of Friedreich ataxia, differential diagnosis of ataxias and genetic counseling, and treatment of neurological and non-neurological symptoms.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1038/nrneurol.2009.26 | DOI Listing |
Neurol Ther
December 2024
Patient-Reported Outcomes and Health Economics Research, Deutsches Zentrum für Neurodegenerative Erkrankungen/German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Ellernholzstrasse 1-2, 17489, Greifswald, Germany.
Introduction: Friedreich Ataxia (FA) is a multisystem neurodegenerative disease. Affected individuals rely on mobility assistive technologies (MAT) (e.g.
View Article and Find Full Text PDFOrphanet J Rare Dis
December 2024
Discovery Research Division, Indian Council of Medical Research (ICMR) Headquarters, V. Ramalingaswami Bhawan, Ansari Nagar, P.O. Box 4911, New Delhi, 110029, India.
Background: Friedreich's ataxia (FA) is a rare genetic disorder caused by silencing of the frataxin gene (FXN), which leads to multiorgan damage. Nrf2 is a regulator of FXN, which is a modulator of oxidative stress in animals and humans. Omaveloxolone (Omav) is an Nrf2 activator and has been reported to have antioxidative potential in various disease conditions.
View Article and Find Full Text PDFNanomaterials (Basel)
December 2024
Center for Genomics and Precision Medicine, Institute of Bioscience and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
Harsh acid oxidation of activated charcoal transforms an insoluble carbon-rich source into water-soluble, disc structures of graphene decorated with multiple oxygen-containing functionalities. We term these pleiotropic nano-enzymes as "pleozymes". A broad redox potential spans many crucial redox reactions including the oxidation of hydrogen sulfide (HS) to polysulfides and thiosulfate, dismutation of the superoxide radical (O*), and oxidation of NADH to NAD.
View Article and Find Full Text PDFFront Cell Dev Biol
December 2024
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, United States.
Background And Objectives: Friedreich's Ataxia (FRDA) is a genetic disease that affects a variety of different tissues. The disease is caused by a mutation in the gene ( which is important for the synthesis of iron-sulfur clusters. The primary pathologies of FRDA are loss of motor control and cardiomyopathy.
View Article and Find Full Text PDFNAR Mol Med
October 2024
Department of Biology, Tufts University, 200 Boston Ave., Medford, MA 02155, USA.
H-DNA is an intramolecular DNA triplex formed by homopurine/homopyrimidine mirror repeats. Since its discovery, the field has advanced from characterizing the structure to discovering its existence and role . H-DNA interacts with cellular machinery in unique ways, stalling DNA and RNA polymerases and causing genome instability.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!