3,011 results match your criteria Friedreich Ataxia

Friedreich ataxia in a family from Mali, West Africa/Friedreich ataxia in a Malian family.

Clin Case Rep 2021 May 24;9(5):e04065. Epub 2021 Mar 24.

Faculté de Médecine et d'Odontostomatologie USTTB Bamako Mali.

Friedreich ataxia is the most common inherited ataxia in the world, but yet to be reported in black African. We report the first genetically confirmed case in a West African family. Studying genetic diseases in populations with diverse backgrounds may give new insights into their pathophysiology for future therapeutic targets. Read More

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Mitochondrial and metabolic dysfunction in Friedreich ataxia: update on pathophysiological relevance and clinical interventions.

Neuronal Signal 2021 Jun 17;5(2):NS20200093. Epub 2021 May 17.

Division of Neurology, Departments of Neurology and Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, U.S.A.

Friedreich ataxia (FRDA) is a recessive disorder resulting from relative deficiency of the mitochondrial protein frataxin. Frataxin functions in the process of iron-sulfur (Fe-S) cluster synthesis. In this review, we update some of the processes downstream of frataxin deficiency that may mediate the pathophysiology. Read More

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Results of a randomized double-blind study evaluating luvadaxistat in adults with Friedreich ataxia.

Ann Clin Transl Neurol 2021 Jun 20;8(6):1343-1352. Epub 2021 May 20.

Friedreich's Ataxia Research Alliance (FARA), Downingtown, Pennsylvania, USA.

Objectives: Friedreich ataxia (FRDA) is a rare disorder with progressive neurodegeneration and cardiomyopathy. Luvadaxistat (also known as TAK-831; NBI-1065844), an inhibitor of the enzyme d-amino acid oxidase, has demonstrated beneficial effects in preclinical models relevant to FRDA. This phase 2, randomized, double-blind, placebo-controlled, parallel-arm study evaluated the efficacy and safety of oral luvadaxistat in adults with FRDA. Read More

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Drp1-dependent peptide reverse mitochondrial fragmentation, a homeostatic response in Friedreich ataxia.

Pharmacol Res Perspect 2021 May;9(3):e00755

Department of Pediatrics and Neurology, University of Pennsylvania, Philadelphia, PA, USA.

Friedreich ataxia is an autosomal recessive, neurodegenerative disease characterized by the deficiency of the iron-sulfur cluster assembly protein frataxin. Loss of this protein impairs mitochondrial function. Mitochondria alter their morphology in response to various stresses; however, such alterations to morphology may be homeostatic or maladaptive depending upon the tissue and disease state. Read More

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Longitudinal structural brain changes in Friedreich ataxia depend on disease severity: the IMAGE-FRDA study.

J Neurol 2021 Apr 15. Epub 2021 Apr 15.

School of Psychological Sciences and Turner Institute for Brain and Mental Health, Monash University, Clayton Campus, Clayton, VIC, 3800, Australia.

Background: Friedreich ataxia is an inherited neurodegenerative disease, with cerebral and cerebellar pathology evident. Despite an increased understanding of its neuropathology, disease progression in this disease remains poorly understood. This study aimed to characterise longitudinal change in brain structure using a multi-modal approach across cerebral and cerebellar grey and white matter. Read More

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Childbirth and motherhood in women with motor disability due to a rare condition: an exploratory study.

Orphanet J Rare Dis 2021 Apr 13;16(1):176. Epub 2021 Apr 13.

Child Psychiatry, Hopital Pitié Salpêtrière APHP and Sorbonne Université, Paris, France.

Background: Rare diseases may result in motor impairment, which in turn may affect parenthood. Our purpose was to evaluate perinatal outcomes, parenting needs, mother-infant interactions and infant development in a set of volunteer women with motor impairment due to a rare disease. In a parenting support institution, we recruited a consecutive series of 22 volunteer pregnant women or young mothers, recorded perinatal outcomes, and followed mother-infant interaction and relationship and infant development up to 14 months postpartum. Read More

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Remember friedreich ataxia even in a toddler with apparently isolated dilated (not hypertrophic!) cardiomyopathy: revisited.

Minerva Pediatr (Torino) 2021 Apr 2. Epub 2021 Apr 2.

European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart HCP, Pediatric Cardiology and Arrhythmia/Syncope Units, Bambino Gesù Children Hospital and Research Institute, Rome, Italy -

Background: Friedreich Ataxia (FRDA) is the most common form of ataxia in late childhood. Neurological manifestations often precede cardiac involvement, presenting mainly as hypertrophic cardiomyopathy.

Methods: We describe a toddler with apparently isolated severe heart failure, successfully managed with heart transplant (HT). Read More

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Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study.

Neurologia (Engl Ed) 2021 Mar 25. Epub 2021 Mar 25.

Servicio de Neurología, Hospital Universitario de Albacete, Albacete, España.

Introduction: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019.

Patients And Methods: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. Read More

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Lessons for clinical trial design in Friedreich's ataxia.

Lancet Neurol 2021 05 23;20(5):330-332. Epub 2021 Mar 23.

NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI 48109, USA; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:

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Progression characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS): a 4-year cohort study.

Lancet Neurol 2021 05 23;20(5):362-372. Epub 2021 Mar 23.

Department of Neurology, RWTH Aachen University, Aachen, Germany; JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich and RWTH Aachen University, Aachen, Germany.

Background: The European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) investigates the natural history of Friedreich's ataxia. We aimed to assess progression characteristics and to identify patient groups with differential progression rates based on longitudinal 4-year data to inform upcoming clinical trials in Friedreich's ataxia.

Methods: EFACTS is a prospective, observational cohort study based on an ongoing and open-ended registry. Read More

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Quantitative Assessment of Friedreich Ataxia via Self-Drinking Activity.

IEEE J Biomed Health Inform 2021 Jun 3;25(6):1985-1996. Epub 2021 Jun 3.

Effective monitoring of the progression of neurodegenerative conditions can be significantly improved by objective assessments. Clinical assessments of conditions such as Friedreich's Ataxia (FA), currently rely on subjective measures commonly practiced in clinics as well as the ability of the affected individual to perform conventional tests of the neurological examination. In this study, we propose an ataxia measuring device, in the form of a pressure canister capable of sensing certain kinetic and kinematic parameters of interest to quantify the impairment levels of participants particularly when engaged in an activity that is closely associated with daily living. Read More

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The Role of Serum Levels of Neurofilament Light (NfL) Chain as a Biomarker in Friedreich Ataxia.

Front Neurosci 2021 2;15:653241. Epub 2021 Mar 2.

Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, United States.

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In vivo survival and differentiation of Friedreich ataxia iPSC-derived sensory neurons transplanted in the adult dorsal root ganglia.

Stem Cells Transl Med 2021 Mar 18. Epub 2021 Mar 18.

Department of Biomedical Engineering, The University of Melbourne, Parkville, Australia.

Friedreich ataxia (FRDA) is an autosomal recessive disease characterized by degeneration of dorsal root ganglia (DRG) sensory neurons, which is due to low levels of the mitochondrial protein Frataxin. To explore cell replacement therapies as a possible approach to treat FRDA, we examined transplantation of sensory neural progenitors derived from human embryonic stem cells (hESC) and FRDA induced pluripotent stem cells (iPSC) into adult rodent DRG regions. Our data showed survival and differentiation of hESC and FRDA iPSC-derived progenitors in the DRG 2 and 8 weeks post-transplantation, respectively. Read More

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Synthesis of 5-[(1H-indol-3-yl)methyl]-1,3,4-oxadiazole-2(3H)-thiones and their protective activity against oxidative stress.

Arch Pharm (Weinheim) 2021 Jun 18;354(6):e2100001. Epub 2021 Mar 18.

Department of Organic Chemistry, Kaunas University of Technology, Kaunas, Lithuania.

A small library of 2-[(1H-indol-3-yl)methyl]-5-(alkylthio)-1,3,4-oxadiazoles was prepared, starting from indole-3-acetic acid methyl ester and its 5-methyl-substituted derivative. The synthetic route involved the formation of intermediate hydrazides, their condensation with carbon disulfide, and intramolecular cyclization to corresponding 5-[(1H-indol-3-yl)methyl]-1,3,4-oxadiazole-2(3H)-thiones. The latter were then S-alkylated, and in case of ester derivatives, they were further hydrolyzed into corresponding carboxylic acids. Read More

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Nuclear Factor Erythroid 2-Related Factor 2 Activation Might Mitigate Clinical Symptoms in Friedreich's Ataxia: Clues of an "Out-Brain Origin" of the Disease From a Family Study.

Front Neurosci 2021 23;15:638810. Epub 2021 Feb 23.

Unit of Muscular and Neurodegenerative Diseases, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.

Friedreich's ataxia (FRDA) is the most frequent autosomal recessive ataxia in western countries, with a mean age of onset at 10-15 years. Patients manifest progressive cerebellar and sensory ataxia, dysarthria, lower limb pyramidal weakness, and other systemic manifestations. Previously, we described a family displaying two expanded GAA alleles not only in the proband affected by late-onset FRDA but also in the two asymptomatic family members: the mother and the younger sister. Read More

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February 2021

Mitochondrial iron and calcium homeostasis in Friedreich ataxia.

IUBMB Life 2021 Mar 5;73(3):543-553. Epub 2021 Mar 5.

Dept. Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, Lleida, Spain.

Friedreich Ataxia is a neuro-cardiodegenerative disease caused by the deficiency of frataxin, a mitochondrial protein. Many evidences indicate that frataxin deficiency causes an unbalance of iron homeostasis. Nevertheless, in the last decade many results also highlighted the importance of calcium unbalance in the deleterious downstream effects caused by frataxin deficiency. Read More

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Future Prospects of Gene Therapy for Friedreich's Ataxia.

Int J Mol Sci 2021 Feb 11;22(4). Epub 2021 Feb 11.

Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, Nicolás Cabrera 1, 28049 Madrid, Spain.

Friedreich's ataxia is an autosomal recessive neurogenetic disease that is mainly associated with atrophy of the spinal cord and progressive neurodegeneration in the cerebellum. The disease is caused by a GAA-expansion in the first intron of the frataxin gene leading to a decreased level of frataxin protein, which results in mitochondrial dysfunction. Currently, there is no effective treatment to delay neurodegeneration in Friedreich's ataxia. Read More

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February 2021

Ectopic Burden via Holter Monitors in Friedreich Ataxia.

Pediatr Neurol 2021 Apr 23;117:29-33. Epub 2021 Jan 23.

Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Friedreich ataxia is the most commonly inherited ataxia; nearly 60% of deaths are cardiac in nature, with one in eight deaths due to arrhythmia. Additional or irregular heartbeats, measured as ectopy, can be quantified using portable heart rhythm monitoring. We sought to describe the ectopic burden in Friedreich ataxia. Read More

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The displacement of frataxin from the mitochondrial cristae correlates with abnormal respiratory supercomplexes formation and bioenergetic defects in cells of Friedreich ataxia patients.

FASEB J 2021 Mar;35(3):e21362

Department of Biology, University of Padova, Padova, Italy.

Friedreich ataxia (FRDA) is a neurodegenerative disease resulting from a severe decrease of frataxin (FXN). Most patients carry a GAA repeat expansion in both alleles of the FXN gene, whereas a small fraction of them are compound heterozygous for the expansion and a point mutation in the other allele. FXN is involved in the mitochondrial biogenesis of the FeS-clusters. Read More

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Safety and feasibility of upper limb cardiopulmonary exercise test in Friedreich ataxia.

Eur J Prev Cardiol 2020 Dec 9. Epub 2020 Dec 9.

Department of Neurosciences, Reproductive and Odontostomatological Sciences (DNSRO), Federico II University, Via S. Pansini 5, Naples, Italy.

Aims: To explore the feasibility of upper limbs cardiopulmonary exercise test (CPET) in Friedreich ataxia (FRDA) patients and to compare the results with sex, age, and body mass index (BMI) matched cohort of healthy controls (HC).

Methods And Results: Cardiopulmonary exercise test was performed using an upper limbs cycle ergometer on fasting subjects. Peak oxygen uptake (peak VO2) was recorded as the mean value of VO2 during a 20 s period at the maximal effort of the test at an appropriate respiratory exchange rate. Read More

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December 2020

Prognostic value of longitudinal strain and ejection fraction in Friedreich's ataxia.

Int J Cardiol 2021 05 14;330:259-265. Epub 2021 Feb 14.

Sorbonne Université, Cardiology Department, AP-HP, Pitié-Salpêtrière University Hospital, Paris, France; ICAN (Institute for Cardiometabolism and Nutrition), Pitié-Salpêtrière University Hospital, Paris, France; ACTION (Allies in Cardiovascular Trials Initiatives and Organized Networks) Group, France. Electronic address:

Background: Friedreich's ataxia (FA) is a rare autosomal recessive mitochondrial disease most commonly due to a triplet repeat expansion guanine-adenine-adenine (GAA) in the FXN gene. Cardiac disease is the major cause of death, patients with reduced left ventricular ejection fraction (LVEF) having the worse prognosis. Longitudinal strain (LS) appeared to be a better predictor of outcome than LVEF in different diseases. Read More

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Modifiers of Somatic Repeat Instability in Mouse Models of Friedreich Ataxia and the Fragile X-Related Disorders: Implications for the Mechanism of Somatic Expansion in Huntington's Disease.

J Huntingtons Dis 2021 ;10(1):149-163

Laboratory of Cell and Molecular Biology, National Institutes of Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.

Huntington's disease (HD) is one of a large group of human disorders that are caused by expanded DNA repeats. These repeat expansion disorders can have repeat units of different size and sequence that can be located in any part of the gene and, while the pathological consequences of the expansion can differ widely, there is evidence to suggest that the underlying mutational mechanism may be similar. In the case of HD, the expanded repeat unit is a CAG trinucleotide located in exon 1 of the huntingtin (HTT) gene, resulting in an expanded polyglutamine tract in the huntingtin protein. Read More

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January 2021

Sensory neuronopathies: new genes, new antibodies and new concepts.

J Neurol Neurosurg Psychiatry 2021 Feb 9. Epub 2021 Feb 9.

Department of Neurology, APHP, CHU de Bicêtre, Le Kremlin-Bicêtre, France.

Degeneration of dorsal root ganglia (DRG) and its central and peripheral projections provokes sensory neuronopathy (SN), a rare disorder with multiple genetic and acquired causes. Clinically, patients with SN usually present with proprioceptive ataxia, patchy and asymmetric sensory abnormalities, widespread areflexia and no weakness. Classic causes of SN include cancer, Sjögren's syndrome, vitamin deficiency, chemotherapy, mitochondrial disorders and Friedreich ataxia. Read More

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February 2021

Gauging Gait Disorders with a Method Inspired by Motor Control Theories: A Pilot Study in Friedreich's Ataxia.

Sensors (Basel) 2021 Feb 6;21(4). Epub 2021 Feb 6.

Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.

To date, it has been challenging for clinicians and researchers alike to use the multiple outcome measures available to create a meaningful clinical picture and perform effective longitudinal follow-up. It has been found that instrumented gait analysis can provide information associated with a patient's performance and help to remedy the shortcomings of the currently available outcome measures. The goal of this methodological article is to set the background and justify a new outcome measure inspired by the motor control theories to analyze gait using spatiotemporal parameters. Read More

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February 2021

Defective palmitoylation of transferrin receptor triggers iron overload in Friedreich ataxia fibroblasts.

Blood 2021 Apr;137(15):2090-2102

UMR1163, Institut Imagine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Friedreich ataxia (FRDA) is a frequent autosomal recessive disease caused by a GAA repeat expansion in the FXN gene encoding frataxin, a mitochondrial protein involved in iron-sulfur cluster (ISC) biogenesis. Resulting frataxin deficiency affects ISC-containing proteins and causes iron to accumulate in the brain and heart of FRDA patients. Here we report on abnormal cellular iron homeostasis in FRDA fibroblasts inducing a massive iron overload in cytosol and mitochondria. Read More

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Eye-tracking-aided characterization of saccades and antisaccades in SYNE1 ataxia patients: a pilot study.

BMC Neurosci 2021 Feb 1;22(1). Epub 2021 Feb 1.

Department of Neurology, University of Szeged, Semmelweis u. 6, 6725, Szeged, Hungary.

Background: SYNE1 ataxia is an autosomal recessive hereditary condition, the main characteristic features of which are gait and limb ataxia and cerebellar dysarthria. Reports have revealed that the clinical phenotype of SYNE1 ataxia is more complex than the first published cases with pure cerebellar signs indicated. The aim of this study was to characterize eye movement alterations in the first diagnosed Hungarian SYNE1 ataxia patients. Read More

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February 2021

Methylated and unmethylated epialleles support variegated epigenetic silencing in Friedreich ataxia.

Hum Mol Genet 2021 02;29(23):3818-3829

Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

Friedreich ataxia (FRDA) is typically caused by homozygosity for an expanded GAA triplet-repeat in intron 1 of the FXN gene, which results in transcriptional deficiency via epigenetic silencing. Most patients are homozygous for alleles containing > 500 triplets, but a subset (~20%) have at least one expanded allele with < 500 triplets and a distinctly milder phenotype. We show that in FRDA DNA methylation spreads upstream from the expanded repeat, further than previously recognized, and establishes an FRDA-specific region of hypermethylation in intron 1 (~90% in FRDA versus < 10% in non-FRDA) as a novel epigenetic signature. Read More

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February 2021

Omaveloxolone: potential new agent for Friedreich ataxia.

Neurodegener Dis Manag 2021 04 12;11(2):91-98. Epub 2021 Jan 12.

Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Friedreich ataxia is a slowly progressive neurodegenerative disorder leading to ataxia, dyscoordination, dysarthria and in many individuals vision and hearing loss. It is associated with cardiomyopathy, the leading cause of death in Friedreich ataxia (FRDA), diabetes and scoliosis. There are no approved therapies, but elucidation of the pathophysiology of FRDA suggest that agents that increase the activity of the transcription factor Nrf2 may provide a mechanism for ameliorating disease progression or severity. Read More

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Hand Dexterity and Pyramidal Dysfunction in Friedreich Ataxia, A Finger Tapping Study.

Mov Disord Clin Pract 2021 Jan 21;8(1):85-91. Epub 2020 Dec 21.

Laboratoire de Cartographie Fonctionnelle du Cerveau, ULB Neuroscience Institute Université libre de Bruxelles (ULB) Brussels Belgium.

Background: Loss of hand dexterity has a profound impact on disability in patients with cerebellar, pyramidal, or extrapyramidal diseases. Analysis of multiple finger tapping (FT) parameters can contribute to identify the underlying physiopathology, while providing a quantitative clinical assessment tool, particularly in patients not reliably evaluated using clinical rating scales. Here, we used an automated method of FT analysis in Friedreich ataxia (FRDA) to disentangle cerebellar (prominent FT rate variability), extrapyramidal (FT progressive amplitude reduction without slowing of tapping rate), and pyramidal (progressive decrease of FT rate and amplitude) contribution to upper limb loss of dexterity. Read More

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January 2021

DNA repair pathways are altered in neural cell models of frataxin deficiency.

Mol Cell Neurosci 2021 03 6;111:103587. Epub 2021 Jan 6.

Departamento Biología Molecular and Centro de Biología Molecular "Severo Ochoa" (UAM-CSIC), Universidad Autónoma de Madrid, 28049 Madrid, Spain; Instituto de Investigación Sanitaria Puerta de Hierro-Majadahonda (IDIPHIM), Spain.

Friedreich's ataxia (FRDA) is a hereditary and predominantly neurodegenerative disease caused by a deficiency of the protein frataxin (FXN). As part of the overall efforts to understand the molecular basis of neurodegeneration in FRDA, a new human neural cell line with doxycycline-induced FXN knockdown was established. This cell line, hereafter referred to as iFKD-SY, is derived from the human neuroblastoma SH-SY5Y and retains the ability to differentiate into mature neuron-like cells. Read More

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