title: Milestones in Friedreich ataxia: more than a century and still learning.
abstract: Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia worldwide. This review highlights the main clinical features, pathophysiological mechanisms, and therapeutic approaches for FRDA patients. The disease is characterized by a combination of neurological involvement (ataxia and neuropathy), cardiomyopathy, skeletal abnormalities, and glucose metabolism disturbances. FRDA is caused by expanded guanine-adenine-adenine (GAA) triplet repeats in the first intron of the frataxin gene (FXN), resulting in reduction of messenger RNA and protein levels of frataxin in different tissues. The molecular and metabolic disturbances, including iron accumulation, lead to pathological changes characterized by spinal cord and dorsal root ganglia atrophy, dentate nucleus atrophy without global cerebellar volume reduction, and hypertrophic cardiomyopathy. DNA analysis is the hallmark for the diagnosis of FRDA. There is no specific treatment to stop the disease progression in FRDA patients. However, a number of drugs are under investigation. Therapeutic approaches intend to improve mitochondrial functioning and to increase FXN expression.
authors: Division of General Neurology and Ataxia Unit, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, Rua Pedro de Toledo 650 Vila Clementino, São Paulo, 04039-002, SP, Brazil, agessandro.junior@unifesp.br.
authors: Agessandro
authors: A
authors: Abrahão
authors: José Luiz
authors: JL
authors: Pedroso
authors: Pedro
authors: P
authors: Braga-Neto
authors: Edson
authors: E
authors: Bor-Seng-Shu
authors: Patricia
authors: P
authors: de Carvalho Aguiar
authors: Orlando Graziani Povoas
authors: OG
authors: Barsottini
mesh_terms: D000818:Animals; D018450:Disease Progression; D005621:Friedreich Ataxia / Q000150:complications* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics; D000096923:Frataxin
chemical_list: D033862:Iron-Binding Proteins; D000096923:Frataxin