2,787 results match your criteria Friedreich Ataxia


Expanding the genetic basis of ataxia.

Nat Genet 2019 04;51(4):580-581

Department of Neurology, University of Michigan, Ann Arbor, MI, USA.

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http://dx.doi.org/10.1038/s41588-019-0387-xDOI Listing

Randomized, double-blind, placebo-controlled study of interferon- 1b in Friedreich Ataxia.

Ann Clin Transl Neurol 2019 Mar 27;6(3):546-553. Epub 2019 Feb 27.

Friedreich's Ataxia Research Alliance 533 W Uwchlan Ave Downingtown Pennsylvania 19335.

Objective: In vitro, in vivo, and open-label studies suggest that interferon gamma (IFN- 1b) may improve clinical features in Friedreich Ataxia through an increase in frataxin levels. The present study evaluates the efficacy and safety of IFN- 1b in the treatment of Friedreich Ataxia through a double-blind, multicenter, placebo-controlled trial.

Methods: Ninety-two subjects with FRDA between 10 and 25 years of age were enrolled. Read More

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http://dx.doi.org/10.1002/acn3.731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414489PMC

Therapeutic Prospects for Friedreich's Ataxia.

Trends Pharmacol Sci 2019 04;40(4):229-233

Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham (UAB), 1825 University Boulevard, Birmingham, AL 35294, USA. Electronic address:

Friedreich's ataxia (FRDA) is a progressive disease affecting multiple organs that is caused by systemic insufficiency of the mitochondrial protein frataxin. Current therapeutic strategies aim to elevate frataxin levels and/or alleviate the consequences of frataxin deficiency. Recent significant advances in the FRDA therapeutic pipeline are bringing patients closer to a cure. Read More

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http://dx.doi.org/10.1016/j.tips.2019.02.001DOI Listing
April 2019
1 Read

Patient-reported outcomes in Friedreich's ataxia after withdrawal from idebenone.

Acta Neurol Scand 2019 Mar 18. Epub 2019 Mar 18.

Department of Molecular Neuroscience, Ataxia Centre, UCL Institute of Neurology, Queen Square, London, UK.

Objectives: Friedreich's ataxia is the most common inherited ataxia, and pathogenesis is known to involve mitochondrial oxidative stress. Idebenone is a potent antioxidant which has already been evaluated in several clinical trials in FRDA, with reports of symptomatic benefit but inconclusive objective results. Following patient consultation on design, we have completed a treatment-withdrawal study to establish whether patients could correctly determine their treatment allocation to placebo or idebenone. Read More

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http://dx.doi.org/10.1111/ane.13088DOI Listing
March 2019
2 Reads

The role of robotic gait training and tDCS in Friedrich ataxia rehabilitation: A case report.

Medicine (Baltimore) 2019 Feb;98(8):e14447

IRCCS Centro Neurolesi "Bonino Pulejo", Messina, Italy.

Rationale: Friedrich ataxia (FA) is the most common inherited neurodegenerative cerebellar ataxic syndrome. In patients with FA, physiotherapy is highly recommended to improve motor function outcome. Cerebellar transcranial direct current stimulation (tDCS) has been demonstrated to be effective in improving symptoms by modulating cerebellar excitability. Read More

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http://Insights.ovid.com/crossref?an=00005792-201902220-0002
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http://dx.doi.org/10.1097/MD.0000000000014447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407999PMC
February 2019
2 Reads

In Vitro interaction between yeast frataxin and superoxide dismutases: Influence of mitochondrial metals.

Biochim Biophys Acta Gen Subj 2019 May 21;1863(5):883-892. Epub 2019 Feb 21.

Interfaces, Traitements, Organisation et Dynamique des Systèmes (ITODYS), CNRS UMR 7086, Univ Paris Diderot, Sorbonne Paris Cité, 15 rue Jean-Antoine de Baïf, F-75205 Paris Cedex 13, France. Electronic address:

Background: Friedreich's ataxia results from a decreased expression of the nuclear gene encoding the mitochondrial protein, frataxin. Frataxin participates in the biosynthesis of iron-sulfur clusters and heme cofactors, as well as in iron storage and protection against oxidative stress. How frataxin interacts with the antioxidant defence components is poorly understood. Read More

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http://dx.doi.org/10.1016/j.bbagen.2019.02.011DOI Listing
May 2019
1 Read
4.381 Impact Factor

Case 3: Gait Instability and Elevated Troponin Level in a 16-year-old Boy.

Pediatr Rev 2019 Feb;40(2):85-87

Department of Pediatrics-Joint Pediatric Heart Care Program, University of Kentucky, Lexington, KY.

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http://dx.doi.org/10.1542/pir.2017-0095DOI Listing
February 2019
1 Read

OGTT is recommended for glucose homeostasis assessments in Friedreich ataxia.

Ann Clin Transl Neurol 2019 Jan 25;6(1):161-166. Epub 2018 Nov 25.

Division of Endocrinology Erasmus Hospital Université Libre de Bruxelles Brussels Belgium.

Diabetes is a common complication of Friedreich ataxia, requiring sensitive diagnostic methods. Here, we compared the performance of different tests that assess glucose tolerance, insulin sensitivity, and -cell function in Friedreich ataxia patients, heterozygous mutation carriers and controls. We find that diabetes is underdiagnosed with fasting glucose alone. Read More

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http://doi.wiley.com/10.1002/acn3.686
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http://dx.doi.org/10.1002/acn3.686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331656PMC
January 2019
8 Reads

Safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia.

Ann Clin Transl Neurol 2019 Jan 10;6(1):15-26. Epub 2018 Nov 10.

Reata Pharmaceuticals 2801 Gateway Drive Suite 150 Irving Texas 75063.

Objective: Previous studies have demonstrated that suppression of Nrf2 in Friedreich ataxia tissues contributes to excess oxidative stress, mitochondrial dysfunction, and reduced ATP production. Omaveloxolone, an Nrf2 activator and NF-kB suppressor, targets dysfunctional inflammatory, metabolic, and bioenergetic pathways. The dose-ranging portion of this Phase 2 study assessed the safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia patients (NCT02255435). Read More

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http://dx.doi.org/10.1002/acn3.660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331199PMC
January 2019
4 Reads

Young adult with Friedreich ataxia.

Heart 2019 Jan 15. Epub 2019 Jan 15.

CMR Unit, Bristol Heart Institute, University of Bristol and University Hospitals Bristol NHS Foundation Trust, Bristol, UK.

Clinical Introduction: A young adult with Friedreich ataxia complaining of exertional breathlessness underwent a cardiological evaluation. On physical examination, high blood pressure and a loud systolic murmur were noted. ECG showed sinus rhythm with voltage criteria for left ventricular hypertrophy (LVH) and T-wave changes in the inferolateral leads. Read More

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http://heart.bmj.com/lookup/doi/10.1136/heartjnl-2018-314387
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http://dx.doi.org/10.1136/heartjnl-2018-314387DOI Listing
January 2019
13 Reads

Structural and functional characterization of a frataxin from a thermophilic organism.

FEBS J 2019 Feb 30;286(3):495-506. Epub 2019 Jan 30.

King's College London, UK.

Frataxins form an interesting family of iron-binding proteins with an almost unique fold and are highly conserved from bacteria to primates. They have a pivotal role in iron-sulfur cluster biogenesis as regulators of the rates of cluster formation, as it is testified by the fact that frataxin absence is incompatible with life and reduced levels of the protein lead to the recessive neurodegenerative disease Friedreich's ataxia. Despite its importance, the structure of frataxin has been solved only from relatively few species. Read More

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http://doi.wiley.com/10.1111/febs.14750
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http://dx.doi.org/10.1111/febs.14750DOI Listing
February 2019
5 Reads

Ferroptosis as a Novel Therapeutic Target for Friedreich's Ataxia.

J Pharmacol Exp Ther 2019 Apr 11;369(1):47-54. Epub 2019 Jan 11.

Department of Pathology and Laboratory Medicine, Children's Hospital Philadelphia, Philadelphia, Pennsylvania (M.G.C., S.X., D.L., T.L., R.B.W.); The Penn Medicine/CHOP Center of Excellence for Friedreich's Ataxia Research, Philadelphia, Pennsylvania (M.G.C., S.X., D.L., T.L., R.B.W.); Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania (L.T., P.W.); Department of Chemistry (D.M.H.), and Perelman School of Medicine (R.B.W.), University of Pennsylvania, Philadelphia, Pennsylvania

Friedreich ataxia (FRDA) is a progressive neuro- and cardio-degenerative disorder characterized by ataxia, sensory loss, and hypertrophic cardiomyopathy. In most cases, the disorder is caused by GAA repeat expansions in the first introns of both alleles of the gene, resulting in decreased expression of the encoded protein, frataxin. Frataxin localizes to the mitochondrial matrix and is required for iron-sulfur-cluster biosynthesis. Read More

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http://dx.doi.org/10.1124/jpet.118.252759DOI Listing
April 2019
20 Reads

Longitudinal evaluation of iron concentration and atrophy in the dentate nuclei in friedreich ataxia.

Mov Disord 2019 Mar 9;34(3):335-343. Epub 2019 Jan 9.

Monash Biomedical Imaging, Monash University, Melbourne, Australia.

Background: Friedreich ataxia is a recessively inherited, progressive neurological disease characterized by impaired mitochondrial iron metabolism. The dentate nuclei of the cerebellum are characteristic sites of neurodegeneration in the disease, but little is known of the longitudinal progression of abnormalities in these structures.

Methods: Using in vivo magnetic resonance imaging, including quantitative susceptibility mapping, we investigated changes in iron concentration and volume in the dentate nuclei in individuals with Friedreich ataxia (n = 20) and healthy controls (n = 18) over a 2-year period. Read More

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http://dx.doi.org/10.1002/mds.27606DOI Listing
March 2019
1 Read

Drug repositioning screening identifies etravirine as a potential therapeutic for friedreich's ataxia.

Mov Disord 2019 Mar 9;34(3):323-334. Epub 2019 Jan 9.

Laboratory of Signal Transduction, Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy.

Background: Friedreich's ataxia is an autosomal-recessive cerebellar ataxia caused by mutation of the frataxin gene, resulting in decreased frataxin expression, mitochondrial dysfunction, and oxidative stress. Currently, no treatment is available for Friedreich's ataxia patients. Given that levels of residual frataxin critically affect disease severity, the main goal of a specific therapy for Friedreich's ataxia is to increase frataxin levels. Read More

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http://dx.doi.org/10.1002/mds.27604DOI Listing
March 2019
22 Reads

A new MRI marker of ataxia with oculomotor apraxia.

Eur J Radiol 2019 Jan 29;110:187-192. Epub 2018 Nov 29.

Hospices Civils de Lyon, Neurology D and Neuro-Ophthalmology Unit, Hôpital Neurologique Pierre Wertheimer, Bron, F-69677, France; Université de Lyon, Lyon 1 University, Lyon, F-69373, France; Lyon Neuroscience Research Center, INSERM U1028 CNRS UMR5292, Team ImpAct, Bron, F-69676, France. Electronic address:

Purpose: Evaluate the specificity and sensitivity of disappearance of susceptibility weighted imaging (SWI) dentate nuclei (DN) hypointensity in oculomotor apraxia patients (AOA).

Method: In this prospective study, 27 patients with autosomal genetic ataxia (AOA (n = 11), Friedreich ataxia and ataxia with vitamin E deficit (n = 4), and dominant genetic ataxia (n = 12)) were included along with fifteen healthy controls. MRIs were qualitatively classified for the presence or absence of DN hypointensity on FLAIR and SWI sequences. Read More

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http://dx.doi.org/10.1016/j.ejrad.2018.11.035DOI Listing
January 2019
3 Reads
2.369 Impact Factor

Differences in the determinants of right ventricular and regional left ventricular long-axis dysfunction in Friedreich ataxia.

PLoS One 2018 31;13(12):e0209410. Epub 2018 Dec 31.

Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Parkville, Victoria, Australia.

Background: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative condition which also has effects on the heart. In 96% of affected individuals FRDA is due to homozygosity of a GAA repeat expansion in intron 1 of the frataxin (FXN) gene. The number of GAA repeats have been shown to relate to disease severity in FRDA, this thought to be via an inverse relationship of GAA repeat number and cellular frataxin levels. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209410PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312254PMC
December 2018

GRP75 overexpression rescues frataxin deficiency and mitochondrial phenotypes in Friedreich Ataxia cellular models.

Hum Mol Genet 2018 Dec 26. Epub 2018 Dec 26.

Department of Pediatrics and Neurology, The Children's Hospital of Philadelphia; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by the deficiency of frataxin, a mitochondrial protein crucial for iron-sulphur cluster biogenesis and ATP production. Currently there is no therapy to slow down the progression of FRDA. Recent evidence indicates that posttranslational regulation of residual frataxin levels can rescue some of the functional deficit of FRDA, raising the possibility of enhancing levels of residual frataxin as a treatment for FRDA. Read More

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https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg
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http://dx.doi.org/10.1093/hmg/ddy448DOI Listing
December 2018
15 Reads

Transcriptional profiling of isogenic Friedreich ataxia neurons and effect of an HDAC inhibitor on disease signatures.

J Biol Chem 2019 Feb 14;294(6):1846-1859. Epub 2018 Dec 14.

From the Departments of Molecular Medicine and

Friedreich ataxia (FRDA) is a neurodegenerative disorder caused by transcriptional silencing of the frataxin () gene, resulting in loss of the essential mitochondrial protein frataxin. Based on the knowledge that a GAA·TTC repeat expansion in the first intron of induces heterochromatin, we previously showed that 2-aminobenzamide-type histone deacetylase inhibitors (HDACi) increase mRNA levels in induced pluripotent stem cell (iPSC)-derived FRDA neurons and in circulating lymphocytes from patients after HDACi oral administration. How the reduced expression of frataxin leads to neurological and other systemic symptoms in FRDA patients remains unclear. Read More

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http://www.jbc.org/lookup/doi/10.1074/jbc.RA118.006515
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http://dx.doi.org/10.1074/jbc.RA118.006515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369281PMC
February 2019
9 Reads

Correction of half the cardiomyocytes fully rescue Friedreich ataxia mitochondrial cardiomyopathy through cell-autonomous mechanisms.

Hum Mol Genet 2019 Apr;28(8):1274-1285

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Department of Translational Medicine and Neurogenetics, Illkirch, France.

Friedreich ataxia (FA) is currently an incurable inherited mitochondrial neurodegenerative disease caused by reduced levels of frataxin. Cardiac failure constitutes the main cause of premature death in FA. While adeno-associated virus-mediated cardiac gene therapy was shown to fully reverse the cardiac and mitochondrial phenotype in mouse models, this was achieved at high dose of vector resulting in the transduction of almost all cardiomyocytes, a dose and biodistribution that is unlikely to be replicated in clinic. Read More

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http://dx.doi.org/10.1093/hmg/ddy427DOI Listing
April 2019
1 Read

Large Interruptions of GAA Repeat Expansion Mutations in Friedreich Ataxia Are Very Rare.

Front Cell Neurosci 2018 21;12:443. Epub 2018 Nov 21.

Ataxia Research Group, Division of Biosciences, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, United Kingdom.

Friedreich ataxia is a multi-system autosomal recessive inherited disorder primarily caused by homozygous GAA repeat expansion mutations within intron 1 of the frataxin gene. The resulting deficiency of frataxin protein leads to progressive mitochondrial dysfunction, oxidative stress, and cell death, with the main affected sites being the large sensory neurons of the dorsal root ganglia and the dentate nucleus of the cerebellum. The GAA repeat expansions may be pure (GAA) in sequence or may be interrupted with regions of non-GAA sequence. Read More

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http://dx.doi.org/10.3389/fncel.2018.00443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258883PMC
November 2018
2 Reads
4.289 Impact Factor

Depressive symptoms in Friedreich ataxia.

Int J Clin Health Psychol 2018 Jan-Apr;18(1):18-26. Epub 2017 Dec 8.

Universidad de La Laguna, Spain.

Almost no attention has been paid to depression in Friedreich ataxia (FRDA), a highly disabling cerebellar degenerative disease. Our aim was to study the presence and the profile of depressive symptoms in FRDA and their relationship with demographic-disease variables and cognitive processing speed. The study groups consisted of 57 patients with a diagnosis of FRDA. Read More

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http://dx.doi.org/10.1016/j.ijchp.2017.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220911PMC
December 2017

Neuroimaging Applications in Chronic Ataxias.

Int Rev Neurobiol 2018 29;143:109-162. Epub 2018 Oct 29.

Nuclear Medicine, "Le Scotte" University Hospital, Siena, Italy.

Magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET) are the main instruments for neuroimaging investigation of patients with chronic ataxia. MRI has a predominant diagnostic role in the single patient, based on the visual detection of three patterns of atrophy, namely, spinal atrophy, cortical cerebellar atrophy and olivopontocerebellar atrophy, which correlate with the aetiologies of inherited or sporadic ataxia. In fact spinal atrophy is observed in Friedreich ataxia, cortical cerebellar atrophy in Ataxia Telangectasia, gluten ataxia and Sporadic Adult Onset Ataxia and olivopontocerebellar atrophy in Multiple System Atrophy cerebellar type. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00747742183011
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http://dx.doi.org/10.1016/bs.irn.2018.09.011DOI Listing
October 2018
12 Reads

FAST-1 antisense RNA epigenetically alters FXN expression.

Sci Rep 2018 Nov 21;8(1):17217. Epub 2018 Nov 21.

Division of Biosciences, Department of Life Sciences, College of Health & Life Sciences, and Synthetic Biology Theme, Institute of Environment, Health & Societies, Brunel University London, Uxbridge, United Kingdom.

Friedreich ataxia (FRDA) is a multisystem genetic disorder caused by GAA repeat expansion mutations within the FXN gene, resulting in heterochromatin formation and deficiency of frataxin protein. Elevated levels of the FXN antisense transcript (FAST-1) have previously been detected in FRDA. To investigate the effects of FAST-1 on the FXN gene expression, we first stably overexpressed FAST-1 in non-FRDA cell lines and then we knocked down FAST-1 in FRDA fibroblast cells. Read More

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http://dx.doi.org/10.1038/s41598-018-35639-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249312PMC
November 2018
5.078 Impact Factor

Cardiac Phenotypes in Hereditary Muscle Disorders: JACC State-of-the-Art Review.

J Am Coll Cardiol 2018 Nov;72(20):2485-2506

Centre for Inherited Cardiovascular Diseases, IRCCS Foundation, University Hospital Policlinico San Matteo, Pavia, Italy.

Hereditary muscular diseases commonly involve the heart. Cardiac manifestations encompass a spectrum of phenotypes, including both cardiomyopathies and rhythm disorders. Common biomarkers suggesting cardiomuscular diseases include increased circulating creatine kinase and/or lactic acid levels or disease-specific metabolic indicators. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S07351097183858
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http://dx.doi.org/10.1016/j.jacc.2018.08.2182DOI Listing
November 2018
22 Reads

The impact of histone post-translational modifications in neurodegenerative diseases.

Biochim Biophys Acta Mol Basis Dis 2018 Oct 20. Epub 2018 Oct 20.

Chemistry Department of Brooklyn College, Brooklyn, New York 11210, United States; Ph.D. Programs in Chemistry, Biochemistry, and Biology, The Graduate Center of the City University of New York, New York 10016, United States. Electronic address:

Every year, neurodegenerative disorders take more than 5000 lives in the US alone. Cures have not yet been found for many of the multitude of neuropathies. The majority of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Parkinson's disease (PD) cases have no known genetic basis. Read More

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http://dx.doi.org/10.1016/j.bbadis.2018.10.019DOI Listing
October 2018
2 Reads

Ion Mobility-Mass Spectrometry Reveals Details of Formation and Structure for GAA·TCC DNA and RNA Triplexes.

J Am Soc Mass Spectrom 2019 Jan 19;30(1):103-112. Epub 2018 Oct 19.

School of Physical Sciences, The University of Adelaide, Adelaide, South Australia, 5005, Australia.

DNA and RNA triplexes are thought to play key roles in a range of cellular processes such as gene regulation and epigenetic remodeling and have been implicated in human disease such as Friedreich's ataxia. In this work, ion mobility-mass spectrometry (IM-MS) is used with supporting UV-visible spectroscopy to investigate DNA triplex assembly, considering stability and specificity, for GAA·TTC oligonucleotide sequences of relevance to Friedreich's ataxia. We demonstrate that, contrary to other examples, parallel triplex structures are favored for these sequences and that stability is enhanced by increasing oligonucleotide length and decreasing pH. Read More

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http://link.springer.com/10.1007/s13361-018-2077-9
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http://dx.doi.org/10.1007/s13361-018-2077-9DOI Listing
January 2019
12 Reads

Developmental and neurodegenerative damage in Friedreich's ataxia.

Eur J Neurol 2019 Mar 5;26(3):483-489. Epub 2018 Dec 5.

Department of Neurology and Neuroimaging Laboratory, School of Medical Sciences, University of Campinas (UNICAMP), Campinas.

Background And Purpose: Friedreich's ataxia (FRDA) is the most common autosomal-recessive ataxia worldwide. It is characterized by early onset, sensory abnormalities and slowly progressive ataxia. All magnetic resonance imaging (MRI)-based studies have focused on the evaluation of adult patients. Read More

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http://dx.doi.org/10.1111/ene.13843DOI Listing
March 2019
28 Reads

Corneal confocal microscopy: Neurologic disease biomarker in Friedreich ataxia.

Ann Neurol 2018 Dec;84(6):893-904

Department of Genetic Medicine, Weill Cornell Medical College, New York, NY.

Objective: Friedreich ataxia (FRDA), an autosomal recessive neurodegenerative disease caused by mutations in the gene encoding for the mitochondrial protein frataxin, is characterized by ataxia and gait instability, immobility, and eventual death. We evaluated corneal confocal microscopy (CCM) quantification of corneal nerve morphology as a novel, noninvasive, in vivo quantitative imaging biomarker for the severity of neurological manifestations in FRDA.

Methods: Corneal nerve fiber density, branch density, and fiber length were quantified in individuals with FRDA (n = 23) and healthy age-matched controls (n = 14). Read More

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http://dx.doi.org/10.1002/ana.25355DOI Listing
December 2018
6 Reads

Automated functional upper limb evaluation of patients with Friedreich ataxia using serious games rehabilitation exercises.

J Neuroeng Rehabil 2018 Oct 4;15(1):87. Epub 2018 Oct 4.

Department of Neurology, Erasme Hospital, Brussels, Belgium.

Background: Friedreich ataxia (FRDA) is a disease with neurological and systemic involvement. Clinical assessment tools commonly used for FRDA become less effective in evaluating decay in patients with advanced FRDA, particularly when they are in a wheelchair. Further motor worsening mainly impairs upper limb function. Read More

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https://jneuroengrehab.biomedcentral.com/articles/10.1186/s1
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http://dx.doi.org/10.1186/s12984-018-0430-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172838PMC
October 2018
2 Reads

Functional and Structural Brain Damage in Friedreich's Ataxia.

Front Neurol 2018 6;9:747. Epub 2018 Sep 6.

Severe Developmental Disabilities Unit, Scientific Institute, IRCCS "Eugenio Medea", Conegliano, Italy.

Friedreich's ataxia (FRDA) is a rare hereditary neurodegenerative disorder caused by a GAA repeat expansion in the gene. There is still no cure or quantitative biomarkers reliaby correlating with the progression rate and disease severity. Investigation of functional and structural alterations characterizing white (WM) and gray matter (GM) in FRDA are needed prerequisite to monitor progression and response to treatment. Read More

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http://dx.doi.org/10.3389/fneur.2018.00747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135889PMC
September 2018
14 Reads

Iron in Friedreich Ataxia: A Central Role in the Pathophysiology or an Epiphenomenon?

Pharmaceuticals (Basel) 2018 Sep 19;11(3). Epub 2018 Sep 19.

Departament de Ciències Mèdiques Bàsiques, IRBLleida, Universitat de Lleida, 25198 Lleida, Spain.

Friedreich ataxia is a neurodegenerative disease with an autosomal recessive inheritance. In most patients, the disease is caused by the presence of trinucleotide GAA expansions in the first intron of the frataxin gene. These expansions cause the decreased expression of this mitochondrial protein. Read More

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http://www.mdpi.com/1424-8247/11/3/89
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http://dx.doi.org/10.3390/ph11030089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161073PMC
September 2018
3 Reads

Sudomotor dysfunction is frequent and correlates with disability in Friedreich ataxia.

Clin Neurophysiol 2018 Nov 31;129(11):2290-2295. Epub 2018 Aug 31.

Departments of Neurology, School of Medical Sciences, University of Campinas - UNICAMP, Campinas, SP, Brazil. Electronic address:

Objectives: To evaluate autonomic symptoms and function in Friedreich's Ataxia (FRDA).

Methods: Twenty-eight FRDA patients and 24 controls underwent clinical/electrophysiological testing. We employed the Friedreich's Ataxia Rating Scale (FARS) and the Scales for Outcomes in Parkinson's Disease: Autonomic Questionnaire-SCOPA-AUT to estimate the intensity of ataxia and autonomic complaints, respectively. Read More

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http://dx.doi.org/10.1016/j.clinph.2018.08.017DOI Listing
November 2018
9 Reads

Rare Diseases Inform Myocardial Phenotypes for Precision Medicine.

Authors:
Calum A Macrae

J Card Fail 2018 10 13;24(10):680-681. Epub 2018 Sep 13.

Department of Cardiovascular Medicine, Genetics and Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address:

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https://linkinghub.elsevier.com/retrieve/pii/S10719164183098
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http://dx.doi.org/10.1016/j.cardfail.2018.09.005DOI Listing
October 2018
13 Reads

Increased Frataxin Expression Induced in Friedreich Ataxia Cells by Platinum TALE-VP64s or Platinum TALE-SunTag.

Mol Ther Nucleic Acids 2018 Sep 27;12:19-32. Epub 2018 Apr 27.

Centre de Recherche du CHU, Québec-Université Laval, Québec, QC, Canada; Département de Médecine Moléculaire, l'Université Laval Québec, Québec, QC, Canada. Electronic address:

Frataxin gene (FXN) expression is reduced in Friedreich's ataxia patients due to an increase in the number of GAA trinucleotides in intron 1. The frataxin protein, encoded by that gene, plays an important role in mitochondria's iron metabolism. Platinum TALE (plTALE) proteins targeting the regulatory region of the FXN gene, fused with a transcriptional activator (TA) such as VP64 or P300, were used to increase the expression of that gene. Read More

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https://www.sciencedirect.com/science/article/pii/S216225311
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https://linkinghub.elsevier.com/retrieve/pii/S21622531183006
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http://dx.doi.org/10.1016/j.omtn.2018.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019861PMC
September 2018
2 Reads

Child Neurology: Friedreich ataxia with upper motor neuron findings: A case study.

Neurology 2018 Aug;91(9):426-428

From the University of Kentucky College of Medicine, Lexington.

A 16-year-old boy with hypertrophic cardiomyopathy, gait abnormalities, and balance problems was found to have Friedreich ataxia. Though Friedreich ataxia typically renders patients areflexic, this child had upper motor neuron findings of spasticity in both lower extremities, with crossed adductors, and 4+ deep tendon reflexes at the patella and Achilles bilaterally. This unusual presentation of an uncommon genetic disorder led to uncertainty of the patient's true diagnosis until genetic testing confirmed that he had 2 alleles with the Friedreich ataxia mutation. Read More

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http://dx.doi.org/10.1212/WNL.0000000000006086DOI Listing
August 2018
13 Reads

Test-retest reliability of an instrumented electronic walkway system (GAITRite) for the measurement of spatio-temporal gait parameters in young patients with Friedreich's ataxia.

Gait Posture 2018 10 20;66:45-50. Epub 2018 Aug 20.

AP-HP, Robert Debré University Hospital, Physical Rehabilitation Department, France; INSERM UMR-S 1141, Robert Debré University Hospital, France.

Background: Friedreich ataxia (FRDA) affects the spatio-temporal parameters (STP) of gait. To our knowledge, proper tools to measure the variability of ataxic gait have not been validated yet. The aims of the present study were: (1) to measure the reproducibility of STP and gait scores in young patients with FRDA and (2) to describe the characteristics of gait parameters in this population. Read More

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http://dx.doi.org/10.1016/j.gaitpost.2018.08.017DOI Listing
October 2018
2 Reads

Fly screens for FA.

Authors:
Ellen P Neff

Lab Anim (NY) 2018 09;47(9):233

Lab Animal, .

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http://dx.doi.org/10.1038/s41684-018-0143-3DOI Listing
September 2018

Nonataxia symptoms in Friedreich Ataxia: Report from the Registry of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS).

Neurology 2018 Sep 10;91(10):e917-e930. Epub 2018 Aug 10.

From the Department of Neurology (K.R., I.D., C.H., C.D., J.B.S.), RWTH Aachen University; JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging (K.R., I.D., C.H., C.D., J.B.S.), Forschungszentrum Jülich GmbH and RWTH Aachen University, Germany; Department of Molecular Neuroscience (P.G.), Ataxia Center, UCL Institute of Neurology, London, UK; Unit of Genetics of Neurodegenerative and Metabolic Diseases (C.M.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; ICM (Brain and Spine Institute) Sorbonne Universités (A.D.), UPMC Univ Paris 06 UMR S 1127, and INSERM U 1127, CNRS UMR 7225 and APHP, Pitié-Salpêtrière University Hospital, Genetic Department, Paris, France; Department of Neurology (S.B.), Medical University Innsbruck, Austria; Department of Neurology (T.K.), Friedrich Baur Institute, University Hospital of the Ludwig-Maximilians-Universität München; German Center for Neurodegenerative Diseases (DZNE) (T.K.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich, Germany; Reference Unit of Hereditary Ataxias and Paraplegias (F.J.R.d.R.G.), Department of Neurology, IdiPAZ, Hospital Universitario La Paz, Madrid, Spain; Department of Neurodegenerative Diseases (L.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (I.G.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G.), Bonn; Department of Neurology (K.B.), Philipps University of Marburg, Germany; and Laboratory of Experimental Neurology (M.P.), Université Libre de Bruxelles, Brussels, Belgium.

Objective: To provide a systematic evaluation of the broad clinical variability in Friedreich ataxia (FRDA), a multisystem disorder presenting mainly with afferent ataxia but also a complex phenotype of nonataxia symptoms.

Methods: From the large database of the European Friedreich's Ataxia Consortium for Translational Studies, 650 patients with genetically confirmed FRDA were included. Detailed data of medical history documentation, questionnaires, and reports on clinical features were analyzed to provide in-depth description of the clinical profile and frequency rates of phenotypical features with a focus on differences between typical-onset and late-onset FRDA. Read More

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http://dx.doi.org/10.1212/WNL.0000000000006121DOI Listing
September 2018
16 Reads

Frataxin Restoration in the Nervous System: Possibilities for Gene Therapy.

Mol Ther 2018 08 30;26(8):1880-1882. Epub 2018 Jun 30.

Division of Neurology, Children's Hospital of Philadelphia, 502 Abramson Research Center, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.

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http://dx.doi.org/10.1016/j.ymthe.2018.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094393PMC
August 2018
1 Read

Activating frataxin expression by single-stranded siRNAs targeting the GAA repeat expansion.

Bioorg Med Chem Lett 2018 09 21;28(17):2850-2855. Epub 2018 Jul 21.

Department of Pharmacology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, United States; Department of Biochemistry, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, United States. Electronic address:

Friedreich's ataxia (FRDA) is an incurable neurodegenerative disorder caused by reduced expression of the mitochondrial protein frataxin (FXN). The genetic cause of the disease is an expanded GAA repeat within the FXN gene. Agents that increase expression of FXN protein are a potential approach to therapy. Read More

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http://dx.doi.org/10.1016/j.bmcl.2018.07.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129981PMC
September 2018
4 Reads

Longitudinal analysis of contrast acuity in Friedreich ataxia.

Neurol Genet 2018 Aug 23;4(4):e250. Epub 2018 Jul 23.

Department of Neurology (A.G.H., D.R.L.), University of Pennsylvania; Divisions of Neurology and Pediatrics (L.A.H., D.R.L.), Children's Hospital of Philadelphia, PA; Department of Neurology (S.P.), University of California at Los Angeles; Departments of Neurology and Pediatrics (K.M.), University of Iowa; Department of Neurology (G.R.W.), Emory University, Atlanta, GA; Department of Neurology (T.Z.), University of South Florida, Tampa Bay; Department of Neurology (S.H.S.), University of Florida, Gainesville; Department of Neurology (T.A.), Houston Methodist Hospital, TX; Murdoch Children's Research Institute (M.B.D.), Melbourne, Victoria, Australia; and Department of Neurology (A.B.), University of Rochester, NY.

Objective: To determine the natural history of contrast acuity in Friedreich ataxia.

Methods: In the Friedreich Ataxia-Clinical Outcome Measures Study, participants (n = 764) underwent binocular high- and low-contrast visual acuity testing at annual study visits. Mixed-effects linear regression was used to model visual acuity as a function of time, with random intercepts and slopes to account for intraindividual correlation of repeated measurements. Read More

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http://dx.doi.org/10.1212/NXG.0000000000000250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066362PMC
August 2018
3 Reads

Double-blind, randomized and controlled trial of EPI-743 in Friedreich's ataxia.

Neurodegener Dis Manag 2018 08 27;8(4):233-242. Epub 2018 Jul 27.

Bioelectron Technology Corporation, Mountain View, CA, 94043 USA.

Aim: To evaluate the safety and clinical effects of EPI-743 in Friedreich's ataxia patients. EPI-743 is a compound that targets oxidoreductase enzymes essential for redox control of metabolism.

Methods: We conducted a multicenter trial that evaluated EPI-743 during a 6-month placebo-controlled phase, followed by an 18-month open-label phase. Read More

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http://dx.doi.org/10.2217/nmt-2018-0013DOI Listing
August 2018
1 Read

Zinc(II) binding on human wild-type ISCU and Met140 variants modulates NFS1 desulfurase activity.

Biochimie 2018 Sep 20;152:211-218. Epub 2018 Jul 20.

Structural Genomics Consortium, Nuffield Department of Clinical Medicine, University of Oxford, OX3 7DQ, UK. Electronic address:

Human de novo iron-sulfur (Fe-S) assembly complex consists of cysteine desulfurase NFS1, accessory protein ISD11, acyl carrier protein ACP, scaffold protein ISCU, and allosteric activator frataxin (FXN). FXN binds the NFS1-ISD11-ACP-ISCU complex (SDAU), to activate the desulfurase activity and Fe-S cluster biosynthesis. In the absence of FXN, the NFS1-ISD11-ACP (SDA) complex was reportedly inhibited by binding of recombinant ISCU. Read More

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http://dx.doi.org/10.1016/j.biochi.2018.07.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098246PMC
September 2018
14 Reads

Impact of Models in the Study and Treatment of Friedreich's Ataxia.

Int J Mol Sci 2018 07 7;19(7). Epub 2018 Jul 7.

Lehrstuhl für Entwicklungsbiologie, Universität Regensburg, 93040 Regensburg, Germany.

has been for over a century the model of choice of several neurobiologists to decipher the formation and development of the nervous system as well as to mirror the pathophysiological conditions of many human neurodegenerative diseases. The rare disease Friedreich’s ataxia (FRDA) is not an exception. Since the isolation of the responsible gene more than two decades ago, the analysis of the fly orthologue has proven to be an excellent avenue to understand the development and progression of the disease, to unravel pivotal mechanisms underpinning the pathology and to identify genes and molecules that might well be either disease biomarkers or promising targets for therapeutic interventions. Read More

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http://dx.doi.org/10.3390/ijms19071989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073496PMC
July 2018
2 Reads

The Etiologies of Chronic Progressive Cerebellar Ataxia in a Korean Population.

J Clin Neurol 2018 Jul;14(3):374-380

Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background And Purpose: The etiologies and frequencies of cerebellar ataxias vary between countries. Our primary aim was to determine the frequency of each diagnostic group of cerebellar ataxia patients in a Korean population.

Methods: We reviewed the medical records of patients who were being followed up between November 1994 and February 2016. Read More

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http://dx.doi.org/10.3988/jcn.2018.14.3.374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032000PMC
July 2018
1 Read

Autonomic function testing in Friedreich's ataxia.

J Neurol 2018 Sep 27;265(9):2015-2022. Epub 2018 Jun 27.

Department of Neurology, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria.

Background: Friedreich ataxia (FRDA) is an inherited movement disorder which manifests with progressive gait instability, sensory loss and cardiomyopathy. Peripheral neuropathy is an established feature of FRDA. At neuropathological examination, a depletion of large, myelinated axons is evident, but also unmyelinated fibers are affected which may result in a variety of sensory and autonomic signs and symptoms. Read More

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http://dx.doi.org/10.1007/s00415-018-8946-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132658PMC
September 2018
16 Reads
3.380 Impact Factor

Friedreich Ataxia: Diagnostic Yield and Minimal Frequency in South Brazil.

Cerebellum 2019 Feb;18(1):147-151

Programa de Pós-Graduação em Saúde da Criança e do Adolescente, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2400, sala 220, Porto Alegre, 90035-003, Brazil.

Friedreich ataxia (FRDA) is an autosomal recessive disorder due to mutations in the FXN gene. FRDA is characterized by the classical triad of ataxia, absent reflexes, and Babinski sign, but atypical presentations might also occur. Our aims were to describe the proportion of FRDA diagnoses in suspected families living in Rio Grande do Sul, South Brazil, and to estimate a minimum frequency of symptomatic subjects. Read More

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http://dx.doi.org/10.1007/s12311-018-0958-xDOI Listing
February 2019

Scales for the clinical evaluation of cerebellar disorders.

Handb Clin Neurol 2018 ;154:329-339

Beatrix Kinderziekenhuis, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Clinical scales represent an important tool not only for the initial grading/scoring of disease and assessment of progression, but also for the quantification of therapeutic effects in clinical trials. There are several scales available for the clinical evaluation of cerebellar symptoms. While some scales have been developed and evaluated for specific cerebellar disorders such as Friedreich ataxia, others reliably capture cerebellar symptoms with no respect to the underlying etiology. Read More

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http://dx.doi.org/10.1016/B978-0-444-63956-1.00020-5DOI Listing
September 2018
1 Read

The neuropathology of the adult cerebellum.

Authors:
Arnulf H Koeppen

Handb Clin Neurol 2018 ;154:129-149

Research, Neurology, and Pathology Services, Veterans Affairs Medical Center and Departments of Neurology and Pathology, Albany Medical College, Albany, NY, United States. Electronic address:

This chapter summarizes the neuropathologic features of nonneoplastic disorders of the adult cerebellum. Gait ataxia and extremity dysmetria are clinical manifestations of diseases that interrupt the complex cerebellar circuitry between the neurons of the cerebellar cortex, the cerebellar nuclei (especially the dentate nuclei), and the inferior olivary nuclei. The cerebellum is a prominent target of several sporadic and hereditary neurodegenerative diseases, including multiple system atrophy, spinocerebellar ataxia, and Friedreich ataxia. Read More

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http://dx.doi.org/10.1016/B978-0-444-63956-1.00008-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279249PMC
September 2018
8 Reads