Friedreich's Ataxia This is an OPML file. It can be used to export all the MedWorm RSS feeds on this topic into your personal RSS reader (usually you have to save this file to your own computer before clicking on an Import OPML command in your own feed reader to upload the file which will then import all the feeds) or it can be used by webmasters to integrate MedWorm feeds with their own website. This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader, such as GoogleReader, or to display this data on your own website or blog. Subscribe to this data using MyMedWorm.Subscribe to this data using GoogleReader.Subscribe to this data using Bloglines.Subscribe to this data using MyYahoo.

This page shows you the latest news and research items in this category.

Erythropoietin Receptor (EpoR) Agonism Is Used to Treat a Wide Range of Disease.
Abstract The erythropoietin receptor (EpoR) was discovered and described in red blood cells (RBCs), stimulating its proliferation and survival. The target in humans for EpoR agonists drugs appears clear-to treat anemia. However, there is evidence of the pleitropic actions of erythropoietin (Epo). For that reason, rhEpo therapy was suggested as a reliable approach for treating a broad range of pathologies, including heart and cardiovascular diseases, neurodegenerative disorders (Parkinson's and Alzheimer's disease), spinal cord injury, stroke, diabetic retinopathy and rare diseases (Friedreich ataxia). Unfortunately...
Source: Molecular Medicine - May 23, 2013 Category: Molecular Biology Authors: Sanchis-Gomar F, Perez-Quilis C, Lippi G Tags: Mol Med Source Type: research

Triple Therapy with Darbepoetin Alfa, Idebenone, and Riboflavin in Friedreich's Ataxia: an Open-Label Trial.
Abstract Minimal objective evidence exists regarding management of Friedreich's ataxia (FRDA). Antioxidant and recombinant human erythropoietin therapies have been considered potential treatments to slow progression of FRDA in a small number of studies. The primary objective of the current study was to test the efficacy, safety, and tolerability of triple therapy-darbepoetin alfa, idebenone, and riboflavin-in FRDA in a clinical pilot study. Patients included in this study were nine females, 16 to 45 years of age (average 28 ± 8), diagnosed with FRDA with confirmed GAA repeat expansion mutations in the FXN gen...
Source: Cerebellum - April 27, 2013 Category: Neuroscience Authors: Arpa J, Sanz-Gallego I, Rodríguez-de-Rivera FJ, Domínguez-Melcón FJ, Prefasi D, Oliva-Navarro J, Moreno-Yangüela M, Pascual-Pascual SI Tags: Cerebellum Source Type: research

Cerebello-cerebral connectivity deficits in Friedreich ataxia.
Abstract Brain pathology in Friedreich ataxia is characterized by progressive degeneration of nervous tissue in the brainstem, cerebellum and cerebellar peduncles. Evidence of cerebral involvement is however equivocal. This brain imaging study investigates cerebello-cerebral white matter connectivity in Friedreich ataxia with diffusion MRI and tractography performed in 13 individuals homozygous for a GAA expansion in intron one of the frataxin gene and 14 age- and gender-matched control participants. New evidence is presented for disrupted cerebello-cerebral connectivity in the disease, leading to secondary effects...
Source: Brain Structure and Function - April 7, 2013 Category: Neuroscience Authors: Zalesky A, Akhlaghi H, Corben LA, Bradshaw JL, Delatycki MB, Storey E, Georgiou-Karistianis N, Egan GF Tags: Brain Struct Funct Source Type: research

Mitochondrial Diseases of the Brain.
Abstract Neurodegenerative disorders are debilitating diseases of the brain, characterized by behavioral, motor and cognitive impairments. Ample evidence underpins mitochondrial dysfunction as a central causal factor in the pathogenesis of neurodegenerative disorders including Parkinson's disease, Huntington's disease, Alzheimer's disease, Amyotrophic lateral sclerosis, Friedreich's ataxia and Charcot-Marie-Tooth disease. In this review, we discuss the role of mitochondrial dysfunction such as bioenergetics defects, mitochondrial DNA mutations, gene mutations, altered mitochondrial dynamics (mitochondrial fusion/fi...
Source: Free Radical Biology and Medicine - April 6, 2013 Category: Biology Authors: Chaturvedi RK, Flint Beal M Tags: Free Radic Biol Med Source Type: research

Triple therapy with deferiprone, idebenone and riboflavin in Friedreich's ataxia – open‐label trial
ConclusionOur results seem to indicate some uncertain benefit on the neurological and heart functions of this triple therapy in FRDA. (Source: Acta Neurologica Scandinavica)
Source: Acta Neurologica Scandinavica - April 1, 2013 Category: Neurology Authors: J. Arpa, I. Sanz‐Gallego, F. J. Rodríguez‐de‐Rivera, F. J. Domínguez‐Melcón, D. Prefasi, J. Oliva‐Navarro, M. Moreno‐Yangüela Tags: Original Article Source Type: research

Insertion mutants in Drosophila melanogaster Hsc20 halt larval growth and lead to reduced iron-sulfur cluster enzyme activities and impaired iron homeostasis.
Abstract Despite the prominence of iron-sulfur cluster (ISC) proteins in bioenergetics, intermediary metabolism, and redox regulation of cellular, mitochondrial, and nuclear processes, these proteins have been given scarce attention in Drosophila. Moreover, biosynthesis and delivery of ISCs to target proteins requires a highly regulated molecular network that spans different cellular compartments. The only Drosophila ISC biosynthetic protein studied to date is frataxin, in attempts to model Friedreich's ataxia, a disease arising from reduced expression of the human frataxin homologue. One of several proteins involv...
Source: Journal of Biological Inorganic Chemistry : JBIC - April 1, 2013 Category: Chemistry Authors: Uhrigshardt H, Rouault TA, Missirlis F Tags: J Biol Inorg Chem Source Type: research

Frataxin Deficiency Leads to Defects in Expression of Antioxidants and Nrf2 Expression in Dorsal Root Ganglia of the Friedreich's Ataxia YG8R Mouse Model
Antioxidants & Redox Signaling , Vol. 0, No. 0. (Source: Antioxidants and Redox Signaling)
Source: Antioxidants and Redox Signaling - March 28, 2013 Category: Research Tags: article Source Type: research

Assessment of upper limb function in young Friedreich ataxia patients compared to control subjects using a new three-dimensional kinematic protocol
Abstract: Background: The assessment of Friedreich ataxia effects on upper limb function in clinical follow-up remains a challenging issue. To complete the usual clinical scales, an upper limb kinematic protocol adapted to Friedreich ataxia children and young adults has been developed and applied to both patients and control subjects.Methods: Nineteen Friedreich ataxia patients (7–24years old) and fifteen healthy controls (9–24) were examined twice during three tasks (drawing, pointing, pro-supination) inspired from the “International Cooperative Ataxia Rating Scale”. A custom-made and adjustable device allowed sta...
Source: Clinical Biomechanics - March 27, 2013 Category: Orthopaedics Authors: Nathalie Maurel, Amadou Diop, Arnaud Gouelle, Corinne Alberti, Isabelle Husson Tags: Papers Source Type: research

What Is The Cost Of Rare Diseases Such As Friedreich's Ataxia?
What is the cost of rare diseases such as Friedreich's Ataxia? By analyzing direct and indirect costs of care research in BioMed Central's open access journal Orphanet Journal of Rare Diseases calculated that conservatively this rare disease costs between Â£11,000 and Â£19,000 per person per year. Proper understanding resource allocation is important in minimizing the effect of Friedreich's Ataxia on people's lives while maximizing their quality of life. Diseases are classified as "rare" if they affect less than 1 in 2000 people... (Source: Health News from Medical News Today)
Source: Health News from Medical News Today - March 1, 2013 Category: Consumer Health News Tags: Genetics Source Type: news

Impact of Friedreich's Ataxia on health-care resource utilization in the United Kingdom and Germany
Conclusion: It is hoped that these estimates of resource utilization, can help in understanding the previously unquantified burden of FRDA. Given the long disease duration, management strategies should seek to minimise the impact of the condition on individuals and their caregivers, while maximising quality of life. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - February 28, 2013 Category: Internal Medicine Authors: Paola GiuntiJulia GreenfieldAlison StevensonMichael ParkinsonJodie HartmannRuediger SandtmannJames PiercyJamie O¿HaraLeo CasasFiona Smith Source Type: research

Non-Ataxic Symptoms Contribute to Gait Dysfunction in Spinocerebellar Ataxias (PD2.009)
CONCLUSIONS: Non-ataxia symptoms, including spasticity, sensory,and motor dysfunction contribute to gait dysfunction in SCAs. Patients should be assessed in a systematic fashion to identify these symptoms. Further research is needed to determine the impact of treating non-ataxic symptoms on the overall function of patients with ataxia.Disclosure: Dr. Vu has nothing to disclose. Dr. Sullivan has nothing to disclose. Dr. Shaw has nothing to disclose. Dr. Jahan has nothing to disclose. Dr. Allison has nothing to disclose. Dr. Staffetti has nothing to disclose. Dr. Gooch has received personal compensation for activities with N...
Source: Neurology - February 14, 2013 Category: Neurology Authors: Vu, T., Sullivan, K., Shaw, J., Jahan, I., Allison, K., Staffetti, J., Gooch, C., Greenstein, P., Zesiewicz, T. Tags: PD2 Movement Disorders: Ataxias Source Type: research

A New Assessment Tool for Ataxia Syndromes: The "STAND" (Scale To Assess Ataxia and Neurologic Dysfunction) (PD2.001)
CONCLUSIONS: The STAND's quantification of non-ataxic neurologic symptoms should provide greater diagnostic and prognostic utility than scales that assess ataxic symptoms alone.Disclosure: Dr. Zesiewicz has received personal compensation for activities with Teva Neuroscience, GE, ProCE, and UCB Pharma as a speaker. Dr. Zesiewicz has received research support from Friedreich's Ataxia Research Alliance, Allon Pharmaceuticals, GlaxoSmithKline, Inc. and UCB Pharma. Dr. Zesiewicz has received research support from Friedreich's Ataxia Research Alliance. Dr. Shaw has nothing to disclose. Dr. Jahan has nothing to disclose. Dr. Sul...
Source: Neurology - February 14, 2013 Category: Neurology Authors: Zesiewicz, T., Shaw, J., Jahan, I., Sullivan, K., Allison, K., Staffetti, J., Greenstein, P., Gooch, C., Vu, T. Tags: PD2 Movement Disorders: Ataxias Source Type: research

The Cerebellum Looks Normal in Friedreich Ataxia [LETTERS]
(Source: American Journal of Neuroradiology)
Source: American Journal of Neuroradiology - February 13, 2013 Category: Radiology Authors: Mascalchi, M. Tags: LETTERS Source Type: research

Cognition in Late-Onset Friedreich Ataxia.
Abstract Friedreich ataxia (FRDA) is the most common hereditary ataxia. Since the discovery of the genetic cause of this disease, the phenotypic spectrum seems to be wider, including late-onset forms such as late-onset Friedreich ataxia-LOFA (25-39 years at onset). The neuropathological and clinical patterns in patients with LOFA are similar to those in patients with typical FRDA, but LOFA patients tend to have an overall milder, slowly evolving disease. Given the lack of data about cognitive performance of LOFA, we aimed to investigate whether differences in age at disease onset may be related also to differences...
Source: Cerebellum - February 9, 2013 Category: Neuroscience Authors: Nieto A, Correia R, de Nóbrega E, Montón F, Barroso J Tags: Cerebellum Source Type: research

Synergistic Effects of Frataxin Point Mutations [Bioenergetics]
Friedreich ataxia is an early-onset multisystemic disease linked to a variety of molecular defects in the nuclear gene FRDA. This gene normally encodes the iron-binding protein frataxin (FXN), which is critical for mitochondrial iron metabolism, global cellular iron homeostasis, and antioxidant protection. In most Friedreich ataxia patients, a large GAA-repeat expansion is present within the first intron of both FRDA alleles, that results in transcriptional silencing ultimately leading to insufficient levels of FXN protein in the mitochondrial matrix and probably other cellular compartments. The lack of FXN in turn impairs...
Source: Journal of Biological Chemistry - February 8, 2013 Category: Chemistry Authors: Li, H., Gakh, O., Smith, D. Y., Ranatunga, W. K., Isaya, G. Tags: Molecular Bases of Disease Source Type: research

The Reciprocal Cerebellar Circuitry in Human Hereditary Ataxia.
Abstract Clinicoanatomic correlation in the spinocerebellar ataxias (SCA) and Friedreich's ataxia (FRDA) is difficult as these diseases differentially affect multiple sites in the central and peripheral nervous systems. A new way to study cerebellar ataxia is the systematic analysis of the "reciprocal cerebellar circuitry" that consists of tightly organized reciprocal connections between Purkinje cells, dentate nuclei (DN), and inferior olivary nuclei (ION). This circuitry is similar to but not identical with the "cerebellar module" in experimental animals. Neurohumoral transmitters operating in the circuitry are b...
Source: Cerebellum - February 7, 2013 Category: Neuroscience Authors: Koeppen AH, Ramirez RL, Bjork ST, Bauer P, Feustel PJ Tags: Cerebellum Source Type: research

The epidemiology of intermittent and chronic ataxia in children in Manitoba, Canada
AimTo determine the epidemiology of chronic ataxia in children in Manitoba, Canada. MethodA retrospective study using multiple sources and disease codes identified children (age 0–16y) with chronic ataxia (>2mo duration or recurrent episodes of ataxia) seen at Winnipeg Children's Hospital from 1991 to 2008. Patients with isolated peripheral nerve diseases, vestibular disorders, or brain tumors were excluded. ResultsWe identified 184 patients (males=females; mean age 15y, SD 7y 8mo) with chronic ataxia. Median age at the presenting symptom onset was 1 year 3 months and at ataxia onset 3 years 1 month. Median durati...
Source: Developmental Medicine and Child Neurology - February 7, 2013 Category: Child Development Authors: Michael S Salman, Esther J Lee, Anindita Tjahjadi, Bernard N Chodirker Tags: Original Article Source Type: research

Rating disease progression of Friedreich's ataxia by the International Cooperative Ataxia Rating Scale: analysis of a 603-patient database
The aim of this cross-sectional study was to analyse disease progression in Friedreich’s ataxia as measured by the International Cooperative Ataxia Rating Scale. Single ratings from 603 patients with Friedreich’s ataxia were analysed as a function of disease duration, age of onset and GAA repeat lengths. The relative contribution of items and subscales to the total score was studied as a function of disease progression. In addition, the scaling properties were assessed using standard statistical measures. Average total scale progression per year depends on the age of disease onset, the time since diagnosis and ...
Source: Brain - January 29, 2013 Category: Neurology Authors: Metz, G., Coppard, N., Cooper, J. M., Delatycki, M. B., Durr, A., Di Prospero, N. A., Giunti, P., Lynch, D. R., Schulz, J. B., Rummey, C., Meier, T. Tags: Original Articles Source Type: research

Friedreich Ataxia: Dysarthria Profile and Clinical Data.
Abstract Friedreich ataxia (FRDA) is the most frequent recessive ataxia in the Western world. Dysarthria is a cardinal feature of FRDA, often leading to severe impairments in daily functioning, but its exact characteristics are only poorly understood so far. We performed a comprehensive evaluation of dysarthria severity and the profile of speech motor deficits in 20 patients with a genetic diagnosis of FRDA based on a carefully selected battery of speaking tasks and two widely used paraspeech tasks, i.e., oral diadochokinesis and sustained vowel productions. Perceptual ratings of the speech samples identified respi...
Source: Cerebellum - January 13, 2013 Category: Neuroscience Authors: Brendel B, Ackermann H, Berg D, Lindig T, Schölderle T, Schöls L, Synofzik M, Ziegler W Tags: Cerebellum Source Type: research

Edison commences EPI-743 Phase IIb Friedreich's ataxia trial
Edison Pharmaceuticals has commenced a Phase IIb clinical trial of EPI-743, an orally bioavailable small molecule being developed for the treatment of Friedreich's ataxia and other inherited mitochondrial diseases. (Source: Drug Development Technology)
Source: Drug Development Technology - January 7, 2013 Category: Pharmaceuticals Source Type: news

Central role and mechanisms of β‐cell dysfunction and death in friedreich ataxia–associated diabetes
Abstract Objective:Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused in almost all cases by homozygosity for a GAA trinucleotide repeat expansion in the frataxin gene. Frataxin is a mitochondrial protein involved in iron homeostasis. FRDA patients have a high prevalence of diabetes, the pathogenesis of which is not known. We aimed to evaluate the relative contribution of insulin resistance and β‐cell failure and the pathogenic mechanisms involved in FRDA diabetes. Methods:Forty‐one FRDA patients, 26 heterozygous carriers of a GAA expansion, and 53 controls underwent oral and intraveno...
Source: Annals of Neurology - December 31, 2012 Category: Neurology Authors: Miriam Cnop, Mariana Igoillo‐Esteve, Myriam Rai, Audrey Begu, Yasmina Serroukh, Chantal Depondt, Anyishai E. Musuaya, Ihsane Marhfour, Laurence Ladrière, Xavier Moles Lopez, Dionysios Lefkaditis, Fabrice Moore, Jean‐Pierre Brion, J. Mark Cooper, Anth Tags: Original Article Source Type: research

[Late-onset Friedreich's ataxia with preservation of osteomuscular reflexes].
PMID: 23233145 [PubMed - in process] (Source: Revista de Neurologia)
Source: Revista de Neurologia - December 16, 2012 Category: Neurology Authors: Garcia-Estevez DA Tags: Rev Neurol Source Type: research

Understanding the Role of the Protein Involved in Friedreich Ataxia♦ [Papers of the Week]
♦ See referenced article, J. Biol. Chem. 2012, 287, 43042–43051 Friedreich ataxia is a rare genetic disease that damages the nervous system and causes movement problems. It usually begins in childhood and worsens with age. The disease involves deficiencies in the protein called frataxin. The protein has homologs in both eukaryotes and prokaryotes, but its function is still unresolved. In this Paper of the Week, a team led by Elena Hidalgo at the Universitat Pompeu Fabra in Spain identified a frataxin homolog in the mitochondria of fission yeast. The investigators found that cells missing the gene for the protein were s...
Source: Journal of Biological Chemistry - December 14, 2012 Category: Chemistry Tags: Molecular Bases of Disease Source Type: research

Functional Consequences of Oculomotor Disorders in Hereditary Cerebellar Ataxias.
Abstract Saccadic eye movements are traditionally cited as an especially successful combination of accuracy and velocity, such high level of performances being believed to be crucial for optimal vision. Although the structures subtending these properties are now well recognized, very little is known about the functional consequences on visually guided behaviors of reduced saccade performances, i.e., slowness and/or inaccuracy. We therefore investigated the impact of such impairments in patients with spino-cerebellar and Friedreich ataxia, i.e., diseases known to affect both saccade parameters. Subjects performed a ...
Source: Cerebellum - December 14, 2012 Category: Neuroscience Authors: Alexandre MF, Rivaud-Péchoux S, Challe G, Durr A, Gaymard B Tags: Cerebellum Source Type: research

Proteome of Frataxin Homolog in Fission Yeast [Gene Regulation]
Friedreich ataxia is a genetic disease caused by deficiencies in frataxin. This protein has homologs not only in higher eukaryotes but also in bacteria, fungi, and plants. The function of this protein is still controversial. We have identified a frataxin homolog in fission yeast, and we have analyzed whether its depletion leads to any of the phenotypes observed in other organisms. Cells deleted in pfh1 are sensitive to growth under aerobic conditions, display increased levels of total iron, hallmarks of oxidative stress such as protein carbonylation, decreased aconitase activity, and lower levels of oxygen consumption comp...
Source: Journal of Biological Chemistry - December 14, 2012 Category: Chemistry Authors: Gabrielli, N., Ayte, J., Hidalgo, E. Tags: Molecular Bases of Disease Source Type: research

Can Telomere Shortening in Human Peripheral Blood Leukocytes Serve as a Disease Biomarker of Friedreich's Ataxia?
Antioxidants & Redox Signaling , Vol. 0, No. 0. (Source: Antioxidants and Redox Signaling)
Source: Antioxidants and Redox Signaling - December 13, 2012 Category: Research Tags: article Source Type: research

Substantia Nigra Echogenicity in Friedreich's Ataxia Patients.
Abstract The aim of this study is to assess the presence of substantia nigra (SN) hypoechogenicity in a cohort of Friedreich's ataxia (FRDA) patients and its possible association with restless syndrome (RLS). Fourteen genetically confirmed FRDA patients and 14 sex- and age-matched healthy controls underwent transcranial sonography examination to evaluate the area of echogenicity of the SN. Both groups were clinically assessed with the essential and additional diagnostic criteria for RLS established by the International RLS Study Group. Ataxia was evaluated using the Scale for the Assessment and Rating of Ataxia. We...
Source: Cerebellum - December 13, 2012 Category: Neuroscience Authors: Sierra M, Infante J, Berciano J Tags: Cerebellum Source Type: research

Autophagy induction extends lifespan and reduces lipids content in response to frataxin silencing in C. elegans.
Abstract Severe mitochondria deficiency leads to a number of devastating degenerative disorders, yet, mild mitochondrial dysfunction in different species, including the nematode Caenorhabditis elegans, can have pro-longevity effects. This apparent paradox indicates that cellular adaptation to partial mitochondrial stress can induce beneficial responses, but how this is achieved is largely unknown. Complete absence of frataxin, the mitochondrial protein defective in patients with Friedreich ataxia, is lethal in C. elegans, while its partial deficiency extends animal lifespan in a p53 dependent manner. In this paper ...
Source: Experimental Gerontology - December 13, 2012 Category: Geriatrics Authors: Schiavi A, Torgovnick A, Kell A, Megalou E, Castelein N, Guccini I, Marzocchella L, Gelino S, Hansen M, Malisan F, Condo' I, Bei R, Rea S, Braeckman BP, Tavernarakis N, Testi R, Ventura N Tags: Exp Gerontol Source Type: research

Form of iron in Friedreich ataxia [Medical Sciences]
There is no effective treatment for the cardiomyopathy of the most common autosomal recessive ataxia, Friedreich ataxia (FA). This disease is due to decreased expression of the mitochondrial protein, frataxin, which leads to alterations in mitochondrial iron (Fe) metabolism. The identification of potentially toxic mitochondrial Fe deposits in FA suggests... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - December 11, 2012 Category: Science Authors: Whitnall, M., Rahmanto, Y. S., Huang, M. L.– H., Saletta, F., Lok, H. C., Gutierrez, L., Lazaro, F. J., Fleming, A. J., St. Pierre, T. G., Mikhael, M. R., Ponka, P., Richardson, D. R. Tags: Biological Sciences Source Type: research

Edison Pharmaceuticals raises $20 million
Edison Pharmaceuticals Inc. closed its sixth round of venture funding after raising $20 million. The Mountain View company is testing treatments for mitochondrial diseases -- Leigh Syndrome and Friedreich's ataxia. It is testing its drug EPI-743 in two mid-stage clinical trials in children. Mitsui & Co. Global Investment Inc. led this round and will put someone -- Edison didn't name the person -- on the drug company's board of directors as part of the financing. Edison is focused on treatments… (Source: bizjournals.com Health Care:Physician Practices headlines)
Source: bizjournals.com Health Care:Physician Practices headlines - November 26, 2012 Category: American Health Authors: Steven E.F. Brown Source Type: research

Genomic deletions and point mutations induced in Saccharomyces cerevisiae by the trinucleotide repeats (GAA·TTC) associated with Friedreich's ataxia.
Abstract Expansion of certain trinucleotide repeats causes several types of human diseases, and such tracts are associated with the formation of deletions and other types of genetic rearrangements in Escherichia coli, yeast, and mammalian cells. Below, we show that long (230 repeats) tracts of the trinucleotide associated with Friedreich's ataxia (GAA·TTC) stimulate both large (>50bp) deletions and point mutations in a reporter gene located more than 1kb from the repetitive tract. Sequence analysis of deletion breakpoints indicates that the deletions reflect non-homologous end joining of double-stranded DNA bre...
Source: DNA Repair - November 20, 2012 Category: Genetics & Stem Cells Authors: Tang W, Dominska M, Gawel M, Greenwell PW, Petes TD Tags: DNA Repair (Amst) Source Type: research

Common data elements for clinical research in Friedreich's ataxia
Abstract To reduce study start‐up time, increase data sharing, and assist investigators conducting clinical studies, the National Institute of Neurological Disorders and Stroke embarked on an initiative to create common data elements for neuroscience clinical research. The Common Data Element Team developed general common data elements, which are commonly collected in clinical studies regardless of therapeutic area, such as demographics. In the present project, we applied such approaches to data collection in Friedreich's ataxia (FRDA), a neurological disorder that involves multiple organ systems. To develop FRDA common ...
Source: Movement Disorders - November 1, 2012 Category: Neurology Authors: David R. Lynch, Massimo Pandolfo, Jorg B. Schulz, Susan Perlman, Martin B. Delatycki, R. Mark Payne, Robert Shaddy, Kenneth H. Fischbeck, Jennifer Farmer, Paul Kantor, Subha V. Raman, Lisa Hunegs, Joanne Odenkirchen, Kristy Miller, Petra Kaufmann Tags: Research Article Source Type: research

Neuroanatomical Correlates of Depression in Friedreich's Ataxia: a Voxel-Based Morphometry Study.
Abstract Affective disorders have been increasingly recognized in neurodegenerative diseases and often result in poor quality of life. However, the frequency, clinical relevance, and anatomical substrate of depression in Friedreich's ataxia were not yet evaluated. We assessed 22 patients with Friedreich's ataxia for major depression using Beck Depression Inventory and cerebral 3 T MRI scans. We then employed whole-brain voxel-based morphometry analyses on volumetric T1 datasets to compare tissue loss between patients with and without major depression. Patients (36.3 %) fulfilled criteria for major depression (8/2...
Source: Cerebellum - October 24, 2012 Category: Neuroscience Authors: da Silva CB, Yasuda CL, D'Abreu A, Cendes F, Lopes-Cendes I, França MC Tags: Cerebellum Source Type: research

Letter by peverill regarding article, "the heart in friedreich ataxia: definition of cardiomyopathy, disease severity, and correlation with neurological symptoms".
PMID: 23091090 [PubMed - in process] (Source: Circulation)
Source: Circulation - October 23, 2012 Category: Cardiology Authors: Peverill RE Tags: Circulation Source Type: research

R- and S-Equol have equivalent cytoprotective effects in Friedreich's Ataxia
Conclusions: These preliminary data demonstrate that estrogen and soy-derived equols could have a beneficial effect in delaying the onset and decreasing the severity of symptoms in FRDA patients by an antioxidant mechanism. In addition, these data confirm that the protection seen previously with E2 was indeed unrelated to ER binding. (Source: BMC Clinical Pharmacology)
Source: BMC Clinical Pharmacology - October 22, 2012 Category: Drugs & Pharmacology Authors: Timothy RichardsonJames Simpkins Source Type: research

Frataxin deficiency unveils cell-context dependent actions of insulin-like growth factor I on neurons
Conclusion: Exposure to IGF-I unveiled a cell-specific regulation of frataxin in neurons as compared to astrocytes. Collectively, these results indicate that IGF-I exerts cell-context neuroprotection in frataxin deficiency that maybe therapeutically effective. (Source: Molecular Neurodegeneration)
Source: Molecular Neurodegeneration - October 5, 2012 Category: Neurology Authors: Carolina FrancoSilvia FernandezIgnacio Torres Aleman Source Type: research

Reviewing the genetic causes of spastic-ataxias
Although the combined presence of ataxia and pyramidal features has a long differential, the presence of a true spastic-ataxia as the predominant clinical syndrome has a rather limited differential diagnosis. Autosomal recessive ataxia of Charlevoix-Saguenay, late-onset Friedreich ataxia, and hereditary spastic paraplegia type 7 are examples of genetic diseases with such a prominent spastic-ataxic syndrome as the clinical hallmark. We review the various causes of spastic-ataxic syndromes with a focus on the genetic disorders, and provide a clinical framework, based on age at onset, mode of inheritance, and additional clini...
Source: Neurology - October 1, 2012 Category: Neurology Authors: de Bot, S. T., Willemsen, M. A. A. P., Vermeer, S., Kremer, H. P. H., van de Warrenburg, B. P. C. Tags: MRI, Gait disorders/ataxia, Spastic paraplegia, Spinocerebellar ataxia, All Genetics VIEWS AND REVIEWS Source Type: research

Auditory pathway changes mirror overall disease progress in individuals with Friedreich ataxia
Content Type Journal ArticleCategory Letter to the EditorsPages 1-3DOI 10.1007/s00415-012-6679-zAuthors Gary Rance, Department of Audiology and Speech Pathology, The University of Melbourne, 550 Swanston Street, Parkville, Melbourne, VIC 3010, AustraliaLouise A. Corben, Bruce Lefroy Centre for Genetic Health Research, Murdoch Children’s Research Institute, Melbourne, AustraliaMartin B. Delatycki, Department of Clinical Genetics, Bruce Lefroy Centre for Genetic Health Research, Murdoch Children’s Research Institute, Austin Health, Melbourne, Australia Journal Journal of NeurologyOnline ISSN 1432-1459Print ISS...
Source: Journal of Neurology - September 30, 2012 Category: Neurology Tags: Journal of Neurology Source Type: research

Relation of Cytosolic Iron Excess to Cardiomyopathy of Friedreich's Ataxia
In conclusion, Fe-mediated damage to cardiomyocytes and myocardial scarring are more likely due to cytosolic Fe excess. (Source: The American Journal of Cardiology)
Source: The American Journal of Cardiology - September 24, 2012 Category: Cardiology Authors: R. Liane Ramirez, Jiang Qian, Paolo Santambrogio, Sonia Levi, Arnulf H. Koeppen Tags: Cardiomyopathy Source Type: research

Study identifies genes associated with genomic expansions that cause disease
(Georgia Institute of Technology Research News) A study of more than 6,000 genes in a common species of yeast has identified the pathways that govern the instability of GAA/TTC repeats. In humans, the expansions of these repeats is known to inactivate a gene - FXN - which leads to Friedreich's ataxia, a neurodegenerative disease that is currently incurable. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - September 9, 2012 Category: Global & Universal Source Type: news

Olfactory impairment in familial ataxias
This study confirms previous findings of mild hyposmia in ataxia, and further suggests this may be due to general cognitive deficits rather than specific olfactory problems. (Source: Journal of Neurology, Neurosurgery and Psychiatry)
Source: Journal of Neurology, Neurosurgery and Psychiatry - September 7, 2012 Category: Neurosurgery Authors: Moscovich, M., Munhoz, R. P., Teive, H. A., Raskin, S., Carvalho, M. d. J., Barbosa, E. R., Ranvaud, R., Liu, J., McFarland, K., Ashizawa, T., Lees, A. J., Silveira-Moriyama, L. Tags: Genetics, Brain stem / cerebellum, Drugs: CNS (not psychiatric), Parkinson's disease, Spinal cord Movement disorders Source Type: research

Sniffing out the cerebellum
The cerebellum is classically considered a primary motor control organ with specific roles in coordination and motor learning. Functional imaging experiments in humans have indicated cerebellar involvement in a host of additional functions such as attention, cognition and, more recently, olfactory processing.1 2 Olfactory dysfunction is present in a number of common neurodegenerative disorders such as Alzheimer's disease (AD) and idiopathic Parkinson's disease (PD) as well as disorders that primarily affect the cerebellum such as spinocerebellar (SCA) and Friedreich's ataxia (figure 1).3–8 Olfactory dysfunction can b...
Source: Journal of Neurology, Neurosurgery and Psychiatry - September 7, 2012 Category: Neurosurgery Authors: Houlden, H. Tags: Genetics, Brain stem / cerebellum, Cranial nerves, Dementia, Drugs: CNS (not psychiatric), Movement disorders (other than Parkinsons), Parkinson's disease, Spinal cord, Ophthalmology, Memory disorders (psychiatry), Mood disorders (including depression), P Source Type: research

A1 Differential diagnosis in relation to Huntington's disease
Davide Martino, Honorary Clinical Lecturer in Neurology, PhD, MD. University of Bari, Italy: MD 1999 Medicine; Specialist Training 2004 Neurology; PhD in Neuroscience 2008, Clinical Neuroscience. Research/professional experience: 1993–1994: Internship, Institute of Biological Chemistry, Medical Faculty, University of Bari, Italy. 1996–1999: Internship, Neurological University Clinic, Policlinico Hospital, Bari, Italy. 1999–2004: Specialist Registrar in Neurology, Neurological University Clinic, Policlinico Hospital, Bari. April 2003 to October 2003: European Marie Curie Research Fellow, Department of Neur...
Source: Journal of Neurology, Neurosurgery and Psychiatry - September 7, 2012 Category: Neurosurgery Authors: Martino, D. Tags: Genetics, Immunology (including allergy), Brain stem / cerebellum, Epilepsy and seizures, Movement disorders (other than Parkinsons), Ophthalmology, Child and adolescent psychiatry, Memory disorders (psychiatry) BNPA 2012 AGM Source Type: research

T.P.15 An open label clinical pilot study of resveratrol as a treatment for Friedreich ataxia
Abstract: Friedreich ataxia (FRDA), the most common hereditary ataxia, is due to a GAA triplet repeat expansion in intron 1 of the FXN gene in about 98% of affected individuals, resulting in deficiency of the mitochondrial protein frataxin. There is no treatment proven to alter its natural history. Resveratrol is a plant-derived compound. It was identified to increase frataxin expression in cellular and mouse models of FRDA, and is proposed to have anti-oxidant and neuroprotective properties. This is an open-label sequential clinical pilot study evaluating the effect of two different doses of resveratrol on lymphocyte frat...
Source: Neuromuscular Disorders - August 31, 2012 Category: Neurology Authors: E.M. Yiu, R. Peverill, G. Tai, C. Stockley, J. Sarsero, M. Evans-Galea, A. Churchyard, L. Corben, K. Lee, M.M. Ryan, M.B. Delatycki Source Type: research

Mismatch Repair in GAA{middle dot}TTC Triplet-repeat Expansion [Molecular Bases of Disease]
The genetic mutation in Friedreich ataxia (FRDA) is a hyperexpansion of the triplet-repeat sequence GAA·TTC within the first intron of the FXN gene. Although yeast and reporter construct models for GAA·TTC triplet-repeat expansion have been reported, studies on FRDA pathogenesis and therapeutic development are limited by the availability of an appropriate cell model in which to study the mechanism of instability of the GAA·TTC triplet repeats in the human genome. Herein, induced pluripotent stem cells (iPSCs) were generated from FRDA patient fibroblasts after transduction with the four transcription factors Oct4, Sox2, ...
Source: Journal of Biological Chemistry - August 24, 2012 Category: Chemistry Authors: Du, J., Campau, E., Soragni, E., Ku, S., Puckett, J. W., Dervan, P. B., Gottesfeld, J. M. Tags: DNA and Chromosomes Source Type: research

MutS{beta} Promotes GAA{middle dot}TTC Expansion [DNA and Chromosomes]
While DNA repair has been implicated in CAG·CTG repeat expansion, its role in the GAA·TTC expansion of Friedreich ataxia (FRDA) is less clear. We have developed a human cellular model that recapitulates the DNA repeat expansion found in FRDA patient tissues. In this model, GAA·TTC repeats expand incrementally and continuously. We have previously shown that the expansion rate is linked to transcription within the repeats. Our working hypothesis is that structures formed within the GAA·TTC repeat during transcription attract DNA repair enzymes that then facilitate the expansion process. MutSβ, a heterodimer of MSH2 and ...
Source: Journal of Biological Chemistry - August 24, 2012 Category: Chemistry Authors: Halabi, A., Ditch, S., Wang, J., Grabczyk, E. Tags: Molecular Bases of Disease Source Type: research

Decreased functional brain activation in Friedreich ataxia using the Simon effect task.
Abstract The present study applied the Simon effect task to examine the pattern of functional brain reorganization in individuals with Friedreich ataxia (FRDA), using functional magnetic resonance imaging (fMRI). Thirteen individuals with FRDA and 14 age and sex matched controls participated, and were required to respond to either congruent or incongruent arrow stimuli, presented either to the left or right of a screen, via laterally-located button press responses. Although the Simon effect (incongruent minus congruent stimuli) showed common regions of activation in both groups, including the superior and middle pr...
Source: Brain and Cognition - August 1, 2012 Category: Neurology Authors: Georgiou-Karistianis N, Akhlaghi H, Corben LA, Delatycki MB, Storey E, Bradshaw JL, Egan GF Tags: Brain Cogn Source Type: research

Levels Of Deficient Protein In Friedreich's Ataxia boosted by New Gene Therapy Strategy
A novel approach to gene therapy that instructs a person's own cells to produce more of a natural disease-fighting protein could offer a solution to treating many genetic disorders. The method was used to achieve a 2- to 3-fold increase in production of a protein deficient in patients with Friedreich's ataxia, as described in an article published Instant Online in Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc. The article is available free online at the Human Gene Therapy website... (Source: Health News from Medical News Today)
Source: Health News from Medical News Today - July 27, 2012 Category: Consumer Health News Tags: Genetics Source Type: news

Human Mesenchymal Stem Cells Increase Anti-oxidant Defences in Cells Derived from Patients with Friedreich's Ataxia.
This study further suggests the potential therapeutic use of MSCs in patients with FRDA. PMID: 22826109 [PubMed - as supplied by publisher] (Source: Cerebellum)
Source: Cerebellum - July 24, 2012 Category: Neuroscience Authors: Dey R, Kemp K, Gray E, Rice C, Scolding N, Wilkins A Tags: Cerebellum Source Type: research

The central role and mechanisms of β‐cell dysfunction and death in Friedreich's ataxia‐associated diabetes
AbstractObjective:Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused in almost all cases by homozygosity for a GAA trinucleotide repeat expansion in the frataxin gene. Frataxin is a mitochondrial protein involved in iron homeostasis. FRDA patients have a high prevalence of diabetes, the pathogenesis of which is not known. We aimed to evaluate the relative contribution of insulin resistance and β‐cell failure and the pathogenic mechanisms involved in FRDA diabetes.Patients and Methods:41 FRDA patients, 26 heterozygous carriers of a GAA expansion and 53 controls underwent oral and IV glu...
Source: Annals of Neurology - July 20, 2012 Category: Neurology Authors: Miriam Cnop, Mariana Igoillo‐Esteve, Myriam Rai, Audrey Begu, Yasmina Serroukh, Chantal Depondt, Anyishai E Musuaya, Ihsane Marhfour, Laurence Ladrière, Xavier Moles Lopez, Dionysios Lefkaditis, Fabrice Moore, Jean‐Pierre Brion, J Mark Cooper, Anthon Tags: Research Article Source Type: research