Voice Disorder in Friedreich Ataxia

UPCOMING EVENTS:
The Voice Foundation’s, 41ST ANNUAL SYMPOSIUM:
CARE OF THE PROFESSIONAL VOICE
May 30 - June 3, 2012, The Westin Philadelphia
Philadelphia, Pennsylvania, USA

AGENDA 2012 MAY 31,Thursday
POSTER SESSION: Voice Disorder in Friedreich Ataxia
Adam Vogel, Mayumi Samahita, Joanne Folker, Bruce Murdoch, Louise Corben, Martin Delatycki

Research on plants for the understanding of diseases of nuclear and mitochondrial origin

Claudia Spampinato1 and Diego F. Gomez-Casati1,2
1Centro de Estudios Fotosintéticos y Bioquímicos (CEFOBI-CONICET), Universidad
Nacional de Rosario, Suipacha 531, 2000, Rosario, Argentina.
2Universidad Nacional de General San Martín (UNSAM), Av. Gral Paz 5445, San
Martín, Buenos Aires, Argentina.

Highlight:
these results allow us to propose Arabidopsis AtFH deficient lines as interesting models for investigate the biogenesis of Fe-S clusters, Fe-S- and heme-containing proteins; as well as for better understanding the FA human disease.

The promise of induced pluripotent stem cells in research and therapy.

Nature. 2012 Jan 18;481(7381):295-305. doi: 10.1038/nature10761.

Robinton DA, Daley GQ.
Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.

Keywords: stem-cell biology, reprogramming technology, pluripotency, reprogramming factors, personalized regenerative cell therapies, embryonic stem cells, therapeutic potential.

Tandem repeats discovery service (TReaDS) applied to finding novel cis-acting factors in repeat expansion diseases

BMC Bioinformatics 2012, 13(Suppl 4):S3 doi:10.1186/1471-2105-13-S4-S3

Marco Pellegrini 1, Maria Elena Renda 1 and Alessio Vecchio 2
1 Istituto di Informatica e Telematica, Consiglio Nazionale delle Ricerche, Pisa I-56124, Italy
2 Dipartimento di Ingegneria dell'Informazione, Università di Pisa, Pisa I-56122, Italy

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Fuzzy tandem repeats as potential cis-regulatory elements in repeat expansion disorders

In [14] we noticed that the locus associated with the unstable trinucleotide repeat in the Frataxin protein mRNA coding sequence (whose abnormal expansion is cause of Frederich's ataxia) was included in a much longer fuzzy TR, detected using the proposed TRStalker system.

The present research originated from the hypothesis that this fact (a long fuzzy TR covering the unstable locus) could be observed in a large number of trinucleotide repeat disorders. Consequently, FTR could be exposed as a novel cis-regulatory element not yet studied in literature.

We employ the tool TReaDS in order to quickly collect and organize the output of several TR finding algorithms into a single easy to read report in support to this hypothesis.

The role of aberrant mitochondrial bioenergetics in diabetic neuropathy.

Neurobiol Dis. 2012 Mar 9. [Epub ahead of print]

Chowdhury SK, Smith DR, Fernyhough P.
Division of Neurodegenerative Disorders, St Boniface Hospital Research Centre, Winnipeg, MB, Canada.

The role of mitochondrial dysfunction in the etiology of diabetic neuropathy is compared with other types of neuropathy with a distal dying-back pathology such as Friedreich ataxia, Charcot-Marie-Tooth ....

Stem cell Research in Friedreich Ataxia

igbmc, Translational Medicine and Neurogenetics
Hélène Puccio, Research Director Inserm

Excellent presentation about stem cells, present research status.

Highlights:
"Regenerative medicine: too early, not scientifically mature"
"CAREFULL: TOO EARLY TO THINK ABOUT THERAPEUTIC APPLICATION"

Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis

BMC Neuroscience 2012, 13:33 doi:10.1186/1471-2202-13-33

Kerry Hunter and Christian Holscher

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"Conclusions:
Our results suggest that these novel incretin analogues cross the BBB and show physiological activity and neurogenesis in the brain, which may be of use as a treatment of neurodegenerative diseases."

Diabetes Mellitus in Children and Adolescents with Genetic Syndromes

Exp Clin Endocrinol Diabetes ; : -DOI: 10.1055/s-0032-1306330

Schmidt, F.; Kapellen, T. M.; Wiegand, S.; Herbst, A.; Wolf, J.; Fröhlich-Reiterer, E. E.; Rabl, W.; Rohrer, T.; Holl, R. W.; for the DPV-Wiss Study Group and the BMBF Competence Network Diabetes.

Keywords: Turner syndrome, Prader-Willi syndrome, Friedreich ataxia, Alström syndrome, Klinefelter syndrome, Pediatric diabetology.

Interferon gamma upregulates frataxin and corrects the functional deficits in a Friedreich ataxia model

Hum. Mol. Genet. (2012) doi: 10.1093/hmg/dds110 First published online: March 23, 2012

Barbara Tomassini1, Gaetano Arcuri1, Silvia Fortuni1, Chiranjeevi Sandi2, Vahid
Ezzatizadeh2, Carlo Casali3, Ivano Condò1, Florence Malisan1, Sahar Al-Mahdawi2,
Mark Pook2 and Roberto Testi1

1 Laboratory of Immunology and Signal Transduction, University of Rome “Tor
Vergata”, 00133 Rome, Italy
2 Division of Biosciences, School of Health Sciences and Social Care, Brunel University,
Uxbridge, UB8 3PH, UK
3 Department of Neurology, University of Rome “La Sapienza”, Polo Pontino, 04100
Latina, Italy

Importantly,in vivo treatment with IFN increases frataxin expression in DRG neurons, prevents their pathological changes and ameliorates the sensorimotor performance in FRDA mice. These results disclose new roles for IFN in cellular metabolism and have direct implications for the treatment of FRDA.


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Mitochondrial quality control: a matter of life and death for neurons

The EMBO Journal (2012) 31, 1336 - 1349, doi:10.1038/emboj.2012.38

Elena I Rugarli 1,2 and Thomas Langer 2,3,4
1 Institute for Zoology, University of Cologne, Cologne, Germany
2 Center for Molecular Medicine (CMMC) and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
3 Institute for Genetics, University of Cologne, Cologne, Germany
4 Max-Planck-Institute for Biology of Aging, Cologne, Germany

Keywords: mitochondria, mitochondrial fusion, mitophagy, mitochondrial proteases, neurodegeneration

Monogenic Mitochondrial Disorders

N Engl J Med 2012; 366:1132-1141March 22, 2012

Werner J.H. Koopman, Ph.D., Peter H.G.M. Willems, Ph.D., and Jan A.M. Smeitink, Ph.D.
From the Department of Biochemistry, Nijmegen Center for Molecular Life Sciences (W.J.H.K., P.H.G.M.W.), and the Department of Pediatrics, Nijmegen Center for Mitochondrial Disorders (J.A.M.S.) — both at Radboud University Medical Center, Nijmegen, the Netherlands.

Review Article

The many faces of insulin-like peptide signalling in the brain

Nature Reviews Neuroscience 13, 225-239 (April 2012) | doi:10.1038/nrn3209

Ana M. Fernandez & Ignacio Torres-Alemán

Keywords: insulin-like peptides (ILPs), insulin, insulin-like growth factor 1 (IGF1) and IGF2, brain, regulate energy homeostasis.

Comment: The IGF-1 has been proposed as a possible FA treatment by several researchers, it have even performed a clinical trial proof of concept, the results has been inconclusive because of its short duration and small number of participants

High Resolution Melting: improvements in the genetic diagnosis of Hypertrophic Cardiomyopathy in a Portuguese cohort

BMC Medical Genetics 2012, 13:17 doi:10.1186/1471-2350-13-17
Susana Santos, Vanda Marques, Marina Pires, Leonor Silveira, Helena Oliveira
Vasco Lanca, Dulce Brito, Hugo Madeira, Esteves J Fonseca, Antonio Freitas,
Isabel M Carreira, Isabel M Gaspar, Carolino Monteiro, Alexandra R Fernandes.

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Keywords: Hypertrophic cardiomyopathy, Gene-based diagnosis, High Resolution Melting, Sarcomere proteins, CSRP3 gen, FXN gene.

Background: Hypertrophic Cardiomyopathy (HCM) is a complex myocardial disorder with a recognized genetic heterogeneity. The elevated number of genes and mutations involved in HCM limits a gene-based diagnosis that should be considered of most importance for basic research and clinical medicine.

Repligen Initiates Phase 1 Clinical Trial of RG2833 in Patients with Friedreich's Ataxia

WALTHAM, MA - March 15, 2012 - Repligen Corporation (NASDAQ:RGEN) announced today that it has enrolled its first patient in a Phase 1 clinical trial of RG2833 in adult patients with Friedreich's ataxia (FA). read more .....

Preimplantation genetic diagnosis (PGD) for Huntington's disease: the experience of three European centres

European Journal of Human Genetics (2012) 20, 368–375; doi:10.1038/ejhg.2011.202.

Maartje C Van Rij, Marjan De Rademaeker, Céline Moutou, Jos CFM Dreesen, Martine De Rycke, Inge Liebaers, Joep PM Geraedts, Christine EM De Die-Smulders and Stéphane Viville.

Keywords: preimplantation genetic diagnosis (PGD); Huntington's disease (HD); HTT gene; exclusion testing; delivery rates; prenatal diagnosis

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Inheritance patterns of the huntington (autosomal dominant) differ from the friedreich's ataxia ​​(autosomal recessive), but sometimes the future parents know that are carriers before the pregnancy, then, this techniques could be useful. (Important note: this is only scientific information, perhaps some people may have ethical objections with these practices)

Do we always prioritize balance when walking? Towards an integrated model of task prioritization

Mov. Disord.. doi: 10.1002/mds.24963

Yogev- Seligmann, G., Hausdorff, J. M. and Giladi, N. (2012), .

Keywords: dual task, postural control, prioritization executive function, motor and cognitive capabilities,  gait, fall risk, neurological diseases.

Expression of axonal protein degradation machinery in sympathetic neurons is regulated by nerve growth factor

J. Neurosci. Res.. (2012) doi: 10.1002/jnr.23041

Frampton, J. P., Guo, C. and Pierchala, B. A.

Keywords: proteasome, lysosome, NGF, transport, autophagy.

In Friedreich's ataxia research currently there is a work line about the frataxin's degradation by the proteasome , the idea is seeking to delay the degradation of frataxin, and therefore lengthen the shelf life.

References:

Preventing the ubiquitin/proteasome-dependent degradation of frataxin, the protein defective in Friedreich’s Ataxia

New project: Identification of the E3 ligase that ubiquitinates frataxin

Cardiac Dysfunction Exacerbated by Endocrinopathies in Friedreich Ataxia: A Case Series.

J Child Neurol. 2012 Mar 8. [Epub ahead of print]

Snyder M, Seyer L, Lynch DR, Resnick A, Zesiewicz TA.

Keywords: Friedreich ataxia, gait abnormalities, cardiomyopathy, diabetes, congestive heart failure, frataxin deficiency, oxidative damage, metabolic syndrome, diabetes.

Exonic Deletions of FXN and Early-Onset Friedreich Ataxia

Arch Neurol. Published online March 12, 2012. doi:10.1001/archneurol.2011.834

Mathieu Anheim, MD, PhD; Louise-Laure Mariani, MD; Patrick Calvas, MD, PhD; Emmanuel Cheuret, MD; Fabien Zagnoli, MD; Sylvie Odent, MD; Claire Seguela, BS; Cecilia Marelli, MD; Marlène Fritsch, BS; Jean-Pierre Delaunoy, PhD; Alexis Brice, MD, PhD; Alexandra Dürr, MD, PhD; Michel Koenig, MD, PhD

Université Pierre et Marie Curie, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS) (Drs Anheim, Marelli, Brice, and Dürr), Assistance publique–Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Department of Genetics and Cytogenetics (Drs Anheim, Mariani, Marelli, Brice, and Dürr), and Centre de Référence des Maladies Neurogénétiques de l'Enfant et de l'Adulte (Drs Anheim, Marelli, Brice, and Dürr), Paris, Service de Génétique Médicale, Université de Toulouse, Hôpital Purpan (Dr Calvas), and Service de neuropédiatrie, Hopital des enfants (Dr Cheuret), Toulouse, Neurologie Hôpital d’Instruction des Armées Clermont-Tonnerre, Brest (Dr Zagnoli), Service de Génétique clinique CHU de Rennes, Université Rennes 1, CNRS (Dr Odent), Laboratoire de Diagnostic Génétique, Nouvel Hôpital Civil, Strasbourg (Mesdames Seguela and Fritsch and Drs Delaunoy and Koenig), and Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, Université de Strasbourg, INSERM, Illkirch (Dr Koenig), France.

Keywords: Friedreich ataxia (FA), early onset, homozygous GAA expansions, FXN gene, point mutation, exonic deletion mutation (FAexdel), confinement to wheelchair, scoliosis, diabetes mellitus, cardiomyopathy.

The effect of lipoic acid and vitamin E therapies in individuals with the metabolic syndrome

Although there are large differences between FA and the metabolic syndrome, mitochondrial function is significantly impaired in both. Many ataxians are taking on a regular basis lipoic acid (ALA) and Vitamin E, it is interesting to know their effects on the heart and on insulin and glucose levels.

Nutrition, Metabolism & Cardiovascular Diseases - 09 March 2012,(10.1016/j.numecd.2011.11.006)

P.J. Manning, W.H.F. Sutherland, S.M. Williams, R.J. Walker, E.A. Berry, S.A. De Jong, A.R. Ryalls
Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand

KEYWORDS: Antioxidant, Metabolic syndrome, Non esterified fatty acids, Lipoic acid, Vitamin E

Evidence for a Role of Frataxin in Pancreatic Islets Isolated from Multi-Organ Donors with and Without Type 2 Diabetes Mellitus.

Horm Metab Res. 2012 Mar 7. [Epub ahead of print]

Del Guerra S, D'Aleo V, Gualtierotti G, Pandolfi R, Boggi U, Vistoli F, Barnini S, Filipponi F, Del Prato S, Lupi R.
Department of Endocrinology and Metabolism, Section of Metabolic Diseases and Diabetes, Pisa University Hospital, Pisa, Italy.

Keywords: Frataxin (FXN), iron metabolism, reactive oxygen and/or nitrogen species, pancreatic islets, Type 2 diabetes mellitus, insulin release, glucose stimulation (SI), nitrotyrosine.

Small biotechs raring to cash in on the orphan disease market

Nature Medicine 18, 330–331 (2012), doi:10.1038/nm0312-330

Friedreich’s Ataxia reveals a mechanism for coordinate regulation of oxidative metabolism via feedback inhibition of the SIRT3 deacetylase

Hum. Mol. Genet. (2012) doi: 10.1093/hmg/dds095 First published online: March 6, 2012

Gregory R. Wagner 1, P. Melanie Pride 2, Clifford M. Babbey 2 and R. Mark Payne1,2

1 Dept. of Medical & Molecular Genetics, 2D ept. of Pediatrics, Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202

Keywords: Friedreich’s Ataxia (FRDA), frataxin, lysine acetylation, mitochondrial function, SIRT3 deacetylase, protein hyperacetylation.

Confused by genetic tests? NIH’s new online tool may help

An online tool launched today by the National Institutes of Health will make it easier to navigate the rapidly changing landscape of genetic tests. The free resource, called the Genetic Testing Registry (GTR), is available at http://www.ncbi.nlm.nih.gov/gtr/.

Friedreich ataxia

Biogenesis of iron-sulfur clusters in mammalian cells: new insights and relevance to human disease

Dis. Model. Mech. March 2012, doi: 10.1242/dmm.009019 vol. 5 no. 2 155-164

Tracey A. Rouault
National Institute of Child Health and Human Development, Bethesda, MD

Keywords: Iron-sulfur (Fe-S) clusters, electron transport, respiratory chain complexes, regulatory sensing, photosynthesis, DNA repair, Friedreich’s ataxia (FRDA), ISCU myopathy, sideroblastic anemia, encephalomyopathy, mitochondrial iron overload.

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Understanding the genetic and molecular pathogenesis of Friedreich’s ataxia through animal and cellular models

Dis. Model. Mech. March 2012, doi: 10.1242/dmm.008706 vol. 5 no. 2 165-176

Alain Martelli 1,2,3,4,5, Marek Napierala 6 and Hélène Puccio 1,2,3,4,5,*
1 Translational Medicine and Neurogenetics, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), 67404, Illkirch, France
2 Inserm, U596, 67400, Illkirch, France
3 CNRS, UMR7104, 67400, Illkirch, France
4 Université de Strasbourg, 67000, Strasbourg, France
5 Collège de France, Chaire de génétique humaine, 67400, Illkirch, France
6 The Department of Molecular Carcinogenesis, Center for Cancer Epigenetics, University of Texas MD Anderson Cancer Center Science Park, Smithville, TX, USA

Keywords: Friedreich’s ataxia (FRDA), frataxin (FXN), GAA.

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Cardiomyopathy in Friedreich's Ataxia: Exemplifying the Challenges Faced by the Cardiologists in the Management of Rare Diseases

CIRCULATIONAHA.112.095364 Published online before print February 29, 2012, doi: 10.1161/​CIRCULATIONAHA.112.095364

Morten Kvistholm Jensen; Henning Bundgaard
The Heart Centre, Rigshospitalet, Copenenhagen, Denmark

Keywords: Friedreich's ataxia (FA), cardiomyopathy, left ventricular hypertrophy (FA-CM), antioxidants, Idebenone, MICONOS study group.

Cardiomyopathy of Friedreich's Ataxia (FRDA).

Ir J Med Sci. 2012 Feb 29. [Epub ahead of print]

Payne RM, Peverill RE.
Indiana University School of Medicine, 1044 W Walnut, R4-302, Indianapolis, IN, 46202, USA, rpayne@iupui.edu.

No abstract available

Selecting and isolating colonies of human induced pluripotent stem cells reprogrammed from adult fibroblasts.

J Vis Exp. 2012 Feb 20;(60). pii: 3416. doi: 10.3791/3416.

Polak U, Hirsch C, Ku S, Gottesfeld J, Dent SY, Napierala M.
Department of Molecular Carcinogenesis and Center for Cancer Epigenetics, University of Texas M.D. Anderson Cancer Center.

Keywords: human adult fibroblasts, human induced pluripotent stem cells (hiPSC), retroviral vectors, Oct3/4, Sox2, Klf4, c-myc (OSKM), Friedreich ataxia.

The Heart in Friedreich Ataxia: Definition of Cardiomyopathy, Disease Severity, and Correlation with Neurological Symptoms

CIRCULATIONAHA.111.059477, Published online before print February 29, 2012, doi: 10.1161/​CIRCULATIONAHA.111.059477

Original Research Article

The Heart in Friedreich Ataxia: Definition of Cardiomyopathy, Disease Severity, and Correlation with Neurological Symptoms

Frank Weidemann 1; Christian Rummey 2; Bart Bijnens 3; Stefan Störk 1; Ruta Jasaityte 4; Jan Dhooge 4; Aigul Baltabaeva 5; George Sutherland 5; Jörg B. Schulz 5; Thomas Meier 2.
1 University of Würzburg, Würzburg, Germany; 2 Santhera Pharmaceuticals, Liestal, Switzerland; 3 ICREA - Universitat Pompeu Fabra, Barcelona, Spain & University of Leuven, Leuven, Belgium; 4 University of Leuven, Leuven, Belgium; 5 St. George's Hospital, London, United Kingdom; 6 University Hospital, RWTH Aachen & JARA-Brain, Aachen, Germany

KEYWORDS: Friedreich ataxia (FA), cardiomyopathy (FA-CM), standard echocardiography, color Doppler myocardial imaging (CDMI), cardiac magnetic resonance imaging (cMRI), electrocardiography (ECG), neurological function.