Clinical management of Friedreich’s Ataxia: a report of two cases

Yannis Dionyssiotis, Athina Kapsokoulou, Anna Danopoulou, Maria Kokolaki & Athina Vadalouka; Spinal Cord Series and Casesvolume 4, Article number: 38 (2018) doi:10.1038/s41394-018-0071-x

We present two cases, a brother (54 years old) and sister (56 years old), with FDRA that are chronically institutionalized for incomplete quadriplegia without spasticity. Gait and postural ataxia, cerebellar dysarthria, oculomotor dysfunction, musculoskeletal deformities, hearing impairment, hypertrophic cardiomyopathy, and diabetes mellitus are also present. Neurological examination reveals extensor plantar responses and diminished to absent tendon reflexes. Both are wheelchair bound, cannot perform daily tasks and need assistance.
Although there is no cure that can alter the natural course of the disease physiotherapy, management of spasticity and neuropathic pain, symptomatic treatment of heart failure and diabetes and nursing care can grant the patients quality of life.

Increased frataxin expression induced in Friedreich ataxia cells by platinum TALE-VP64s or platinum TALE-SunTag

Khadija Cherif, Catherine Gérard, Joël Rousseau, Dominique L. Ouellet, Pierre Chapdelaine, Jacques P. Tremblay, Molecular Therapy - Nucleic Acids, Available online 27 April 2018, ISSN 2162-2531, doi:10.1016/j.omtn.2018.04.009

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. Many effectors plTALEVP64, plTALEp300 and plTALESunTag targeting 14 sequences of the FXN gene promoter or intron 1 were produced. This permitted to select 3 plTALEVP64s and 2 plTALESunTag that increased FXN gene expression by up to 19 folds in different FRDA primary fibroblasts. Adeno-Associated Viruses were used to deliver the best effectors to the YG8R mouse model to validate their efficiencies in vivo. Our results showed that these selected plTALEVP64s or plTALESunTag induced transcriptional activity of the endogenous FXN gene as well as expression of the frataxin protein in YG8R mouse heart by 10 folds and in skeletal muscles by up to 35 folds. The aconitase activity is positively modulated by the frataxin level in mitochondria and was thus increased in vitro and in vivo by the increased frataxin expression.

BMN 290 for Friedreich's Ataxia

SAN RAFAEL, Calif., April 25, 2018 /PRNewswire

In the fourth quarter of 2017, BioMarin announced that it had selected as its next clinical drug development candidate, BMN 290, a selective chromatin modulation therapy intended for treatment of Friedreich's ataxia. Friedreich's ataxia is a rare autosomal recessive disorder that results in disabling neurologic and cardiac progressive decline associated with a deficiency in frataxin. Prior to the lead compound being acquired by BioMarin from Repligen Corporation (Repligen), it demonstrated increases in frataxin in Friedreich's ataxia patients. On the basis of these results, the Company selected an improved candidate, BMN 290, for its favorable penetration into the central nervous system and cardiac target tissues, and its preservation of the selectivity of the original Repligen compound. In preclinical models conducted by BioMarin, BMN 290, a compound derived from the original Repligen compound, increases frataxin message expression in brain tissues more than two-fold. Currently, there are no approved disease modifying therapies for Friedreich's ataxia. The Company expects to submit the IND application for BMN 290 in the second half of 2018.

Reata Announces New Preclinical Data Demonstrating the Potential of Omaveloxolone in the Treatment of Friedreich’s Ataxia and Other Severe Neurological Diseases

IRVING, Texas, April 24, 2018 (GLOBE NEWSWIRE) -- Reata Pharmaceuticals, Inc. (Nasdaq:RETA) (Reata or Company), a clinical-stage biopharmaceutical company, today announced new preclinical data demonstrating that omaveloxolone potently activates the Keap1/Nrf2 pathway, significantly reduces production of reactive oxygen species, and improves mitochondrial function in two different models of severe neurological diseases. These results support the rationale for clinical studies of omaveloxolone in neurodegenerative and neuromuscular disorders, including the ongoing pivotal MOXIe trial in patients with Friedreich’s ataxia.

Patient reported outcome measures in rare diseases: a narrative review

Anita Slade, Fatima Isa, Derek Kyte, Tanya Pankhurst, Larissa Kerecuk, James Ferguson, Graham Lipkin and Melanie Calvert, Orphanet Journal of Rare Diseases 2018 13:61 doi:10.1186/s13023-018-0810-x

Rare diseases can lead to a significant reduction in quality of life for patients and their families. Ensuring the patients voice is central to clinical decision making is key to delivering, evaluating and understanding the efficacy of therapeutic interventions. Patient reported outcome measures (PROMs) are used to capture the patient’s views about their health status and facilitate our understanding of the impact of these diseases and their treatments on patient’s quality of life and symptoms.

Emergence of breath testing as a new non-invasive diagnostic modality for neurodegenerative diseases

N. Siva Subramaniam, C.S. Bawden, H. Waldvogel, R.M.L. Faull, G.S. Howarth, R.G. Snell, , Brain Research, Available online 22 April 2018, ISSN 0006-8993, doi:10.1016/j.brainres.2018.04.017.

Neurodegenerative diseases (NDDs) are incapacitating disorders that result in progressive motor and cognitive impairment. These disease include Alzheimer’s disease the most common cause of dementia, frontotemporal dementia, amyotrophic lateral sclerosis, dementia with Lewy bodies, Parkinson’s, Huntington’s, Friedreich’s ataxia, and prion disease.
The use of breath testing, as a means of monitoring neurodegenerative disease onset and progression, has the potential to have a significant impact on augmenting the diagnosis of NDDs as the approach is non-invasive, relatively cost effective and straight forward to implement. This review highlights key features of current diagnostic methods utilised to identif.

The idebenone metabolite QS10 restores electron transfer in complex I and coenzyme Q defects

Valentina Giorgio, Marco Schiavone, Chiara Galber, Marco Carini, Tatiana Da Ros, Valeria Petronilli, Francesco Argenton, Valerio Carelli, Manuel J. Acosta Lopez, Leonardo Salviati, Maurizio Prato, Paolo Bernardi, Biochimica et Biophysica Acta (BBA) - Bioenergetics, Available online 22 April 2018, ISSN 0005-2728, doi:10.1016/j.bbabio.2018.04.006.

Here we have studied the effects of quinones generated during in vivo metabolism of idebenone with specific emphasis on 6-(9-carboxynonyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (QS10). QS10 partially restored respiration in cells deficient of complex I or of CoQ without inducing the mitochondrial permeability transition, a detrimental effect of idebenone that may offset its potential benefits.

GoFAR reinforces partnership with Powell Gene Therapy Center at University of Florida (UF) to develop a gene therapy for Friedreich’s ataxia

Torino-Italia, April 20-2018. In January, GoFAR awarded an additional grant of $450,000 to Manuela Corti, P.T., Ph.D., assistant professor of Dr. Barry Byrne M.D., Ph.D director of the UF Powell Gene Therapy Center. GoFAR originally began a collaboration with the UF Powell Gene Therapy Center in 2016 to develop AVV-mediated gene therapy for FA awarding a grant of $750,000.The total award of $1.2Ml has been staged to reach milestones toward the clinical implantation of the therapeutic strategy for FA. The most recent award will be used to complete preclinical studies and prepare data for submission to the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Italian regulatory authority, Instituto Superiore della Sanità (ISS). Hopefully trials are expected to begin later this year.

International advocacy group GoFAR funds UF Health research for Friedreich’s ataxia gene therapy program


GoFAR reinforces partnership with Powell Gene Therapy Center at University of Florida (UF) to develop a gene therapy for Friedreich’s ataxia

Retrotope Announces Peer-Reviewed Publication of Positive Phase 1b/2a Findings for RT001 in Friedreich’s Ataxia

Retrotope, April 18, 2018.
Protocol for Pivotal Clinical Trial Has Been Submitted to the US FDA
LOS ALTOS, Calif., April 18, 2018 (GLOBE NEWSWIRE) -- Retrotope announced today peer-reviewed publication of positive Phase 1b/2a trial results for the company's lead candidate, RT001, in patients with Friedreich's ataxia (FA). RT001 is the first in class of a new category of drugs called D-PUFAs (deuterated polyunsaturated fatty acids), which are designed to protect against free radical damage resulting in cell death that is a hallmark of several degenerative diseases, including FA. In an article titled, "Randomized, Clinical Trial of RT001: Early Signals of Efficacy in Friedreich's Ataxia" (DOI:10.1002/mds.27353), appearing online in Movement Disorders, results of the randomized, double-blind, comparator-controlled Phase 1b/2a trial demonstrated early signals of drug effect (including statistically significant improvements in peak exercise workload compared to placebo) and positive safety and tolerability.

Could stem cell therapy be an effective treatment for Friedreich’s ataxia?

University of Bristol, Press release issued: 17 April 2018

Researchers at the University of Bristol are looking for people with an inherited neurological condition called Friedreich's ataxia (FA) to take part in a study into whether a stem cell therapy could be a treatment for FA.
The small, pilot study aims to recruit seven people to find out if the bone marrow stem cell mobilising drug, granulocyte-colony stimulating factor (GCSF), could improve blood markers and potentially treat the condition.

Could statins ease deadly heart condition in rare neuromuscular disease?

AAS and EurekAlert, Public Release: 17-Apr-2018.  University of Pennsylvania School of Medicine.
PHILADELPHIA - In preclinical studies using cell models that mimicked liver cells of patients with the rare disease Friedreich's ataxia (FA), a widely used cholesterol-lowering drug increased a precursor of HDL (high-density lipoprotein), the "good cholesterol," according to new research published in PLOS ONE from the Perelman School of Medicine at the University of Pennsylvania. Statins may be able to help Friedreich's ataxia patients increase their naturally low ApoA-I levels and so increase their HDL levels, which might help prevent heart disease.

Mitochondria in the nervous system: From Health to disease, part II

Maria Teresa Carrì, Brian M. Polster, Philip M. Beart, Mitochondria in the nervous system: From Health to disease, part II, Neurochemistry International, Available online 10 April 2018, ISSN 0197-0186, doi:10.1016/j.neuint.2018.04.006.

In Part II of this Special Issue on "Mitochondria in the Nervous System: From Health to Disease", the editors bring together more reviews and original articles from researchers in the field of mitochondrial metabolism in the healthy and diseased nervous system. Subjects span from basic mitochondrial physiology to papers on mitochondrial dynamics and to those altered states of the nervous system that can be considered “mitopathologies”. Finally, a few papers approach aspects of mitochondrial biology linked to the feasibility and validity of a mitochondrial therapy.

The fact that lack of a single protein affects all of these processes supports the concept that they are all interconnected, albeit it is difficult to pinpoint the “primum movens” in the chain of events leading to neurodegeneration. Furthermore, Friedreich's ataxia is another example of a disease where mutations in a gene coding for a ubiquitously expressed protein mostly affect a specific tissue or cell type.

Caso práctico enfermería: Intento de autolisis en Ataxia de Friedreich

Rocío del Carmen Ortiz Gutiérrez; Laura Quintana Pérez; María Romero Palomar; Revista Médica Electrónica PortalesMedicos.com, 10 abril, 2018


Con un plan de cuidados de enfermería, junto con el trabajo del resto de profesionales del equipo multidisciplinar, el ingreso en la unidad de agudos de la paciente ha resultado satisfactoria, en cuanto al afrontamiento de su patología crónica.
No obstante, se derivará a la unidad de salud mental de su centro de atención primaria, para posterior seguimiento. Se aconseja a su vez la asistencia a asociaciones de afectados de Ataxia de Friedreich para socialización con pacientes de igual a igual.

Silent pauses in aphasia

Georgia Angelopoulou, Dimitrios Kasselimis, George Makrydakis, Maria Varkanitsa, Petros Roussos, Dionysis Goutsos, Ioannis Evdokimidis, Constantin Potagas, Neuropsychologia, Available online 7 April 2018, ISSN 0028-3932, doi:10.1016/j.neuropsychologia.2018.04.006.

Several studies have demonstrated that pausing may be affected by neurological conditions. Individuals with amyotrophic lateral sclerosis and Friedreich’s Ataxia have been shown to produce longer pauses in conversational speech compared to controls. These studies clearly show prominent differences in pausing between healthy participants and pathological populations. These studies have also demonstrated how pausing measures may be used as diagnostic markers and/or as markers of cognitive changes over time. Taken together, these findings suggest that pauses could be an integral aspect of cognitive assessment in clinical practice and research.

Randomized, clinical trial of RT001: Early signals of efficacy in Friedreich's ataxia

Theresa Zesiewicz MD, FAAN, Frederic Heerinckx MPharm, Robert De Jager MD, FACP, Omid Omidvar MD, Marcus Kilpatrick PhD, Jessica Shaw MPH, Mikhail S. Shchepinov PhD, Movement Disorders : Official Journal of the Movement Disorder Society, First published: 6 April 2018 doi:10.1002/mds.27353

RT001 was found to be safe and tolerable over 28 days, and improved peak workload. Further research into the effect of RT001 in Friedreich's ataxia is warranted.

Strong correlations among four measures of disease progression in Friedreich's ataxia

Harry J. Saal PhD, Frederic Heerinckx, Rezi Zawadzki DrPH, Omid Omidvar MD, Marcus Kilpatrick PhD, Theresa Zesiewicz MD, Movement Disorders : Official Journal of the Movement Disorder Society [06 Apr 2018] Letter DOI: 10.1002/mds.27351

Using the data from a double-blind, placebo-controlled trial in 19 FRDA patients testing RT001 a linoleic acid derivative, baseline FARS-Neuro scores were compared with T25FW and CPET to measure peak workload/kg and peak oxygen consumption.

Drosophila melanogaster Models of Friedreich’s Ataxia

P. Calap-Quintana, J. A. Navarro, J. González-Fernández, M. J. Martínez-Sebastián, M. D. Moltó, and J. V. Llorens, BioMed Research International, vol. 2018, Article ID 5065190, 20 pages, 2018. doi:10.1155/2018/5065190

FXN is evolutionarily conserved, with orthologs in essentially all eukaryotes and some prokaryotes, leading to the development of experimental models of this disease in different organisms. These FRDA models have contributed substantially to our current knowledge of frataxin function and the pathogenesis of the disease, as well as to explorations of suitable treatments. Drosophila melanogaster, an organism that is easy to manipulate genetically, has also become important in FRDA research. This review describes the substantial contribution of Drosophila to FRDA research since the characterization of the fly frataxin ortholog more than 15 years ago. Fly models have provided a comprehensive characterization of the defects associated with frataxin deficiency and have revealed genetic modifiers of disease phenotypes. In addition, these models are now being used in the search for potential therapeutic compounds for the treatment of this severe and still incurable disease.

Clinical and genetic aspects of defects in the mitochondrial iron–sulfur cluster synthesis pathway

Vanlander, A.V. & Van Coster, R. J Biol Inorg Chem (2018). doi:10.1007/s00775-018-1550-z

Iron–sulfur clusters are evolutionarily conserved biological structures which play an important role as cofactor for multiple enzymes in eukaryotic cells. The biosynthesis pathways of the iron–sulfur clusters are located in the mitochondria and in the cytosol. The mitochondrial iron–sulfur cluster biosynthesis pathway (ISC) can be divided into at least twenty enzymatic steps. Since the description of frataxin deficiency as the cause of Friedreich’s ataxia, multiple other deficiencies in ISC biosynthesis pathway have been reported. In this paper, an overview is given of the clinical, biochemical and genetic aspects reported in humans affected by a defect in iron–sulfur cluster biosynthesis.

Brain mitochondrial iron accumulates in Huntington's disease, mediates mitochondrial dysfunction, and can be removed pharmacologically

Sonal Agrawal, Julia Fox, Baskaran Thyagarajan, Jonathan Fox, Free Radical Biology and Medicine, Available online 4 April 2018, ISSN 0891-5849, doi:10.1016/j.freeradbiomed.2018.04.002.

We demonstrate here that human Huntington's disease and mouse model HD (12-week R6/2 and 12-month YAC128) brains accumulated mitochondrial iron and showed increased expression of iron uptake protein mitoferrin 2 and decreased iron-sulfur cluster synthesis protein frataxin.

Friedreich Ataxia Scientific News: Monthly update: March 8- April 5, 2018

Monthly update: March 8- April 5, 2018 The transcriptional regulator CCCTC-binding factor limits oxidative stress in endothelial cells Suggest a potential mechanism for endothelial dysfunction in FRDA. Read more »

Idebenone: Novel Strategies to Improve Its Systemic and Local Efficacy Liposomes, cyclodextrins and lipid-based nanoparticles could open new perspectives in the therapeutic outcomes of this strong antioxidant agent. Read more »

Impact of Mobility Device Use on Quality of Life in Children With Friedreich Ataxia Mobility device use is associated with significant worsening of all domains of quality of life in children with Friedreich ataxia. Read more »

Management of Pediatric Movement Disorders: Present and Future Treatment such as gene therapy, epigenetic modulation, and stem cell therapy hold promise for improving outcomes in both primary and secondary causes of movement disorders. Read more »

Structure and mechanism of mitochondrial electron transport chain This work provided solid evidence for the existence of megacomplex of human respirasome. This is a great step forward into conquering many severe neurodegenerative diseases, including Alzheimer's syndrome, Parkinson's disease, multiple sclerosis, friedreich's ataxia, Amyotrophic lateral sclerosis, etc. Read more »

Dysfunction in the mitochondrial Fe-S assembly machinery leads to formation of the chemoresistant truncated VDAC1 isoform without HIF-1α activation We show that hypoxia promotes the downregulation of several proteins (ISCU, NFS1, FXN) involved in the early steps of mitochondrial Fe-S cluster biogenesis. Read more »

Rapid exhaustion of auditory neural conduction in a prototypical mitochondrial disease, Friedreich ataxia A large decrease in conduction velocity along auditory neurons occurs within seconds, attributed to fast energetic failure. Read more »

Cell Therapy Instigates Neural Repair In Friedreich’s Ataxia Mice Transplantation of bone marrow cells that express frataxin into the FRDA mice caused the upregulation of frataxin as well as a number of antioxidative proteins, as well as improving movement and coordination in the mice. Read more »

Assistance circulatoire et transplantation d’organes thoraciques chez l’enfant Les maladies neuro-dégénératives (Friedreich, Duchenne) ou certaines maladies mitochondriales, ainsi que des séquelles graves d'accident vasculaire cérébral, sont considérées comme des contre-indications à la greffe. Read more »

Caractéristiques cliniques ; électrophysiologiques et évolutives des formes atypiques de l’ataxie héréditaire de Friedreich : à propos sept cas Devant un tableau d’ataxie atypique avec un début tardif et des réflexes vifs ou conservés l’ataxie de Freidreich doit être évoquée et une étude génétique doit être envisagée. Read more »

L’accumulation intracérébrale de fer, un aspect IRM atypique de l’ataxie de Friedreich L’AF devrait systématiquement être envisagée devant un syndrome cérébelleux lentement progressif même chez les sujets âgés et même en l’absence d’antécédent familial en cas de dépôt de fer au niveau du cervelet ou des noyaux gris centraux à l’IRM. Read more »

L’atteinte du système nerveux périphérique au cours des ataxies cérébelleuses héréditaires autosomiques récessives (ACAR) : étude de 33 cas Read more »

Étude de la population réunionnaise atteinte d’ataxie de Friedreich La Réunion possède un cluster d’ataxie de Friedreich à faible nombre de répétition GAA, dont les caractéristiques peuvent rappeler les formes acadiennes, qui sont également le résultat d’un effet fondateur. Read more »

Mitofusin-Dependent ER Stress Triggers Glial Dysfunction and Nervous System Degeneration in a Drosophila Model of Friedreich’s Ataxia Marf and ER stress represent a hub in the neurodegenerative process of FRDA and uncover both as important elements substantially involved the FRDA pathology. Read more »

Identification of p38 MAPK as a novel therapeutic target for Friedreich’s ataxia The involvement of the p38 MAPK pathway in the pathogenesis of FRDA and the potential use of p38 inhibitors as a treatment for FRDA. Read more »

Mutations in PMPCB Encoding the Catalytic Subunit of the Mitochondrial Presequence Protease Cause Neurodegeneration in Early Childhood Biallelic mutations in PMPCB cause defects in MPP proteolytic activity leading to dysregulation of iron-sulfur cluster biogenesis and triggering a complex neurological phenotype of neurodegeneration in early childhood. Read more »

Iron regulatory protein deficiency compromises mitochondrial function in murine embryonic fibroblasts Overexpression of human ISCU and frataxin in Irp1 or Irp2-null cells was able to rescue the defects in iron-sulfur cluster biogenesis and mitochondrial quality. Read more »

Frataxin overexpression in Müller cells protects retinal ganglion cells in a mouse model of ischemia/reperfusion injury in vivo The aim of this study was to evaluate the effect of frataxin overexpression in Müller cells on neuronal survival after retinal ischemia/reperfusion in the mouse in vivo. Read more »

Genetic Infiltrative Cardiomyopathies Friedreich ataxia: cardiac dysfunction from congestive heart failure or arrhythmia accounts for an estimated 59% of death.  Read more »

Resting-state connectivity in neurodegenerative disorders: Is there potential for an imaging biomarker? For rare neurodegenerative diseases, no clear conclusions can be drawn due to the few published results.  Read more »

Optical coherence tomography in autosomal recessive spastic ataxia of Charlevoix-Saguenay This is a useful tool in identifying cases of autosomal recessive spastic ataxia of Charlevoix-Saguenay from other causes of ataxia. Read more »

Distinct effects of frataxin missence point mutations on mitochondrial localization, protein processing, and cellular metabolism These studies will examine the mechanism by which FRDA-associated missense mutations impair FXN processing and explore the influence they have on cellular metabolism, in addition to exploring the use of fatty acids as a potential therapeutic strategy. Read more »

Interactions of iron-bound frataxin with ISCU and ferredoxin on the cysteine desulfurase complex leading to Fe-S cluster assembly Our results show that FXN tightly binds a single Fe2+ but not Fe3+. While FXN (with or without bound Fe2+) does not bind the scaffold protein ISCU directly. Read more »

Biomarcadores epigenéticos: hacia su implantación en la rutina clínica / Epigenetic biomarkers: towards their incorporation into clinical routine En un futuro cercano, este tipo de tecnologías se incorporarán a los laboratorios clínicos y, por lo tanto, el uso de estos biomarcadores se implementará en la rutina de diagnóstico clínico, contribuyendo así a la aplicación real de la teragnosis y mejorando la medicina de precisión. Read more »

Large-scale computational drug repositioning to find treatments for rare diseases eMatchSite is combined with virtual screening to systematically explore opportunities to reposition known drugs to proteins associated with rare diseases. Read more »

The transcriptional regulator CCCTC-binding factor limits oxidative stress in endothelial cells

Anna R Roy, Abdalla Ahmed, Peter V DiStefano, Lijun Chi, Nadiya Khyzha, Niels Galjart, Michael D Wilson, Jason E Fish and Paul Delgado Olguin; J. Biol. Chem., First Published on April 2, 2018 doi: 10.1074/jbc.M117.814699

Ctcf promotes vascular development, and limits oxidative stress in endothelial cells. These results reveal a function for Ctcf in vascular development, and suggest a potential mechanism for endothelial dysfunction in FRDA.

Idebenone: Novel Strategies to Improve Its Systemic and Local Efficacy

Lucia Montenegro, Rita Turnaturi, Carmela Parenti and Lorella Pasquinucci; Nanomaterials 2018, 8(2), 87; doi:10.3390/nano8020087

Due to IDE poor bioavailability after oral and topical administration, many researchers attempted different strategies to increase IDE efficacy in the treatment of neurodegenerative diseases and skin disorders. IDE chemical modifications mainly focused on increasing IDE activity at cellular or mitochondrial level while nanotechnology approaches aimed at designing novel formulations to improve IDE systemic and local efficacy. The encouraging results obtained loading IDE in different delivery systems such as liposomes, cyclodextrins and lipid-based nanoparticles could open new perspectives in the therapeutic outcomes of this strong antioxidant agent

Impact of Mobility Device Use on Quality of Life in Children With Friedreich Ataxia

Resham Ejaz, MD, Shiyi Chen, MSc, Charles J. Isaacs, BA, , Amanda Carnevale, MSc, Judith Wilson, RN(EC), MN, NP-Paediatrics, Kristen George, NP-Paediatrics, Martin B. Delatycki, MBBS, FRACP, PhD, Susan L. Perlman, MD, Katherine D. Mathews, MD, George R. Wilmot, MD, PhD, J. Chad Hoyle, MD, Sub H. Subramony, MD, Theresa Zesiewicz, MD, Jennifer M. Farmer, MS, , David R. Lynch, MD, PhD, , , Grace Yoon, MD, FRCPC, Journal of Child Neurology First Published April 2, 2018 doi:10.1177/0883073818764941

Mobility device use is associated with significant worsening of all domains of quality of life in children with Friedreich ataxia.