Frataxin knockdown in human astrocytes triggers cell death and the release of factors that cause neuronal toxicity

Frataxin knockdown in human astrocytes triggers cell death and the release of factors that cause neuronal toxicity. Frida Loría, Javier Díaz-Nido, Neurobiology of Disease, Available online 29 December 2014, ISSN 0969-9961, http://dx.doi.org/10.1016/j.nbd.2014.12.017.

Findings confirm a detrimental effect of frataxin silencing, not only for astrocytes, but also for neuron-glia interactions, underlining the need to take into account the role of non-cell autonomous processes in FA.

Selective dendritic susceptibility to bioenergetic and redox perturbations in cortical neurons

Selective dendritic susceptibility to bioenergetic and redox perturbations in cortical neurons. Philip Hasel, Sean Mckay, Jing Qiu, Giles E. Hardingham; Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Available online 22 December 2014, ISSN 0167-4889, http://dx.doi.org/10.1016/j.bbamcr.2014.12.021.

Deregulation of glutathione homeostasis and other antioxidant systems is implicated in the aetiology of several neurodegenerative disorders associated with dendritic pathologies, including: Alzheimer's disease, Huntington's disease, ALS Friedreich's ataxia, and Parkinson's disease, and activation of GSH pathway enzymes, particularly in astrocytes, is a potential therapeutic strategy for combating oxidative stress in the brain.

Transition of Thalassaemia and Friedreich ataxia from fatal to chronic diseases

Transition of Thalassaemia and Friedreich ataxia from fatal to chronic diseases. Annita Kolnagou, Christina N Kontoghiorghe, and George J Kontoghiorghes; World J Methodol. Dec 26, 2014; 4(4): 197–218. Published online Dec 26, 2014. doi: 10.5662/wjm.v4.i4.197

Highly specific ubiquitin-competing molecules effectively promote frataxin accumulation and partially rescue the aconitase defect in Friedreich ataxia cells

Highly specific ubiquitin-competing molecules effectively promote frataxin accumulation and partially rescue the aconitase defect in Friedreich ataxia cells. Alessandra Rufini, Francesca Cavallo, Ivano Condo’, Silvia Fortuni, Gabriella De Martino, Ottaviano Incani, Almerinda Di Venere, Monica Benini, Damiano Sergio Massaro, Gaetano Arcuri, Dario Serio, Florence Malisan, Roberto Testi; Neurobiology of Disease, Available online 27 December 2014, ISSN 0969-9961, http://dx.doi.org/10.1016/j.nbd.2014.12.011.

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Identical mutation associated with distinct clinical phenotypes of Friedreich’s ataxia: case report

Identical mutation associated with distinct clinical phenotypes of Friedreich’s ataxia: case report . M. Malenica, M. Kukuruzović, S. Bitanga, G. Krakar, B. Valent, Lj. Cvitanović-Šojat; Paediatr Croat. 2014;58:291-4 DOI: http://dx.doi.org/10.13112/PC.2014.51

The cases of our patients prove that it is not advisable to foresee the clinical course based solely on thenumber of repeats.

Grant Alert: Elucidating the molecular basis of gene silencing by an ORC-HP1 interaction and their contribution to human health disorders

Grant Alert: Elucidating the molecular basis of gene silencing by an ORC-HP1 interaction and their contribution to human health disorders. Christian Speck (Principal Investigator), Till Bartke (Co-Investigator), Richard J Festenstein (Co-Investigator); Source: RCUK Grant #BBM0037601, Organisation: Imperial College London (BBSRC award)

Misregulation of 'heterochromatin' and HP1 is involved in several diseases, including epigenetic diseases such as Friedreich's Ataxia or Facioscapulohumeral muscular dystrophy.

Molecular genetic analysis of Trinucleotide Repeat Disorders (TRDs) in Indian population and application of repeat primed PCR

Molecular genetic analysis of Trinucleotide Repeat Disorders (TRDs) in Indian population and application of repeat primed PCR. Aneek Das Bhowmik, Savithri Rangaswamiah, G. Srinivas, Ashwin B. Dalal, European Journal of Medical Genetics, Available online 19 December 2014, ISSN 1769-7212, http://dx.doi.org/10.1016/j.ejmg.2014.12.010.

Characterization of the Cardiac Phenotype of Friedreich's Ataxia (FRDA)

Characterization of the Cardiac Phenotype of Friedreich's Ataxia (FRDA). ClinicalTrials.gov, Verified December 2014 by Weill Medical College of Cornell University

ClinicalTrials.gov identifier: NCT02316314
Sponsors and Collaborators: Weill Medical College of Cornell University
Principal Investigator: Ronald Crystal, MD

Assembly of Fe/S proteins in bacterial systems ☆: Biochemistry of the bacterial ISC system

Assembly of Fe/S proteins in bacterial systems ☆: Biochemistry of the bacterial ISC system. B. Blanc, C. Gerez, S. Ollagnier de Choudens; Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Available online 13 December 2014, ISSN 0167-4889, http://dx.doi.org/10.1016/j.bbamcr.2014.12.009.

Terapia ocupacional en ataxia de friedreich

Terapia ocupacional en ataxia de friedreich. Ana Cristina Martín Pérez, Dolores Moreno Antequera; Revista electrónica de terapia ocupacional Galicia, TOG, ISSN-e 1885-527X, Nº. 20 (Noviembre), 2014


Occupational therapy in friedreich ataxia (Paper in Spanish)

The objective of this article is to present management "Framework for the practice of occupational therapy (domains and processes) and contrast their utility for assessment, diagnosis and intervention in the area of basic and instrumental activities of daily living daily, leisure time and social participation

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Iron Metabolism and Related Disorders

Iron Metabolism and Related Disorders. K. Hoda, C.L. Bowlus, T.W. Chu and J.R. Gruen, In Reference Module in Biomedical Sciences, Elsevier, 2014, Current as of 1 December 2014, ISBN 9780128012383, http://dx.doi.org/10.1016/B978-0-12-801238-3.05573-2.

Fast-Tracking the Development of Effective Therapeutics in Mitochondrial Medicine

Fast-Tracking the Development of Effective Therapeutics in Mitochondrial Medicine. S P Hersh, Clinical Pharmacology & Therapeutics (2014); 96 6, 641–643. doi:10.1038/clpt.2014.163.

Helix–Coil Transition Induced by Metal Ion Interaction with a Grafted Iron–Binding Site of the CyaY Protein Family

Helix–Coil Transition Induced by Metal Ion Interaction with a Grafted Iron–Binding Site of the CyaY Protein Family. Diego Sebastián Vazquez, William Armando Agudelo, Angel Yone, Nora Vizioli, Martín Arán, Luis Gonzalez Flecha, Mariano Camilo González Lebrero and Javier Santos; Dalton Trans., 2014,
DOI: 10.1039/C4DT02796E

These results contribute to an understanding of the iron–binding mechanisms in proteins and, in particular, in the case of human frataxin.

Protecting the mitochondrial powerhouse

Protecting the mitochondrial powerhouse. Morten Scheibye-Knudsen, Evandro F. Fang, Deborah L. Croteau, David M. Wilson III, Vilhelm A. Bohr; Trends in Cell Biology, Available online 11 December 2014, ISSN 0962-8924, http://dx.doi.org/10.1016/j.tcb.2014.11.002.

Keywords: mitochondria; DNA repair; mitophagy; reactive oxygen species; disease

Principled compassion, 'right to try'

Principled compassion, 'right to try' . Editorial, Nature Medicine 20, 1355 (2014) doi:10.1038/nm.3772

As the momentum of right-to-try legislation demonstrates, the public increasingly demands access to the compassionate use of investigational treatments, and companies and regulators need to adapt to this new reality.

A methodological framework for drug development in rare diseases

A methodological framework for drug development in rare diseases. Patrice Nony, Polina Kurbatova, Agathe Bajard, Salma Malik, Charlotte Castellan, Sylvie Chabaud, Vitaly Volpert, Nathalie Eymard, Behrouz Kassai, Catherine Cornu and The CRESim and Epi-CRESim study groups; Orphanet Journal of Rare Diseases 2014, 9:164 doi:10.1186/s13023-014-0164-y

OPEN ACCES, FULL TEXT PDF

Monitoring Cardiac Function During Idebenone Therapy in Friedreich's Ataxia

Monitoring Cardiac Function During Idebenone Therapy in Friedreich's Ataxia. Di Salvo Giovanni, Pergola Valeria, Fadel Bahaa and Al Fayyadh Majid; Curr Pharm Des. 2014;21(4):479-83. DOI: 10.2174/138161282104141204142917

The iron-binding CyaY and IscX proteins assist the ISC-catalyzed Fe-S 1 biogenesis in Escherichia coli

The iron-binding CyaY and IscX proteins assist the ISC-catalyzed Fe-S 1 biogenesis in Escherichia coli. Béatrice Roche, Allison Huguenot, Frédéric Barras and Béatrice Py; Molecular Microbiology (Accepted Article)2014, DOI: 10.1111/mmi.12888

The Mitochondria in Heart Failure: A Target for Coenzyme Q10 Therapy?

The Mitochondria in Heart Failure: A Target for Coenzyme Q10 Therapy?. A Mortensen and A L Mortensen, Clinical Pharmacology & Therapeutics 96, 645-647 (December 2014) | doi:10.1038/clpt.2014.175

Pharmaceutical pricing, cost containment and new treatments for rare diseases in children

Pharmaceutical pricing, cost containment and new treatments for rare diseases in children. Peter Stella and Gabrielle Gold-von Simson; Orphanet Journal of Rare Diseases 2014, 9:152 doi:10.1186/s13023-014-0152-2

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Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress

Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress. Shaughnessy DT, McAllister K, Worth L, Haugen AC, Meyer JN, Domann FE, Van Houten B, Mostoslavsky R, Bultman SJ, Baccarelli AA, Begley TJ, Sobol RW, Hirschey MD, Ideker T, Santos JH, Copeland WC, Tice RR, Balshaw DM, Tyson FL.; Environ Health Perspect 122:1271–1278; http://dx.doi.org/10.1289/ehp.1408418

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Ataxia

Ataxia. Umar Akbar, Tetsuo Ashizawa, Neurologic Clinics, Volume 33, Issue 1, February 2015, Pages 225-248, ISSN 0733-8619, http://dx.doi.org/10.1016/j.ncl.2014.09.004.

Keywords: Ataxia; Inherited; Sporadic; Autosomal dominant; Autosomal recessive; Mitochondrial; Diagnosis; Treatment

Topoisomerase I Plays a Critical Role in Suppressing Genome Instability at a Highly Transcribed G-Quadruplex-Forming Sequence

Topoisomerase I Plays a Critical Role in Suppressing Genome Instability at a Highly Transcribed G-Quadruplex-Forming Sequence . Puja Yadav, Victoria Harcy, Juan Lucas Argueso, Margaret Dominska, Sue Jinks-Robertson, Nayun Kim; PLoS Genet 10(12): e1004839. doi:10.1371/journal.pgen.1004839

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Genomic instability at purine-rich GAA•TTC repeats and CAG•CTG repeats, which can fold into three-stranded H-DNA and a slipped hairpin structure, forms the molecular basis of multiple neurodegenerative diseases, such as Freidreich's Ataxia and Huntington's disease, respectively.

Hawking's speech software goes open source for disabled

Hawking's speech software goes open source for disabled. Phys-Org News 12/2014

The system that helps Stephen Hawking communicate with the outside world will be made available online from January in a move that could help millions of motor neurone disease sufferers, scientists said Tuesday.

Friedreich ataxia in chinese population (short note)

Friedreich ataxia in chinese population. Dr Xuefeng Pan, Dr Xuefeng Pan's Web Log


We have identified at least two cases of Friedreich ataxia in chinese population in chinese mainland, our findings for the first time unraveled a fact that Chinese people are also vulnerable to Friedreich ataxia

Consensus clinical management guidelines for Friedreich ataxia

Consensus clinical management guidelines for Friedreich ataxia.. Louise A Corben, David Lynch, Massimo Pandolfo, Jörg B Schulz, Martin B Delatycki and On behalf of the Clinical Management Guidelines Writing Group; Orphanet Journal of Rare Diseases 2014, 9:184 doi:10.1186/s13023-014-0184-7

OPEN ACCESS (Summary of recommendations and process of developing the guidelines).

FARA FUNDED: Awesome document with the support of FARA. A knowledge upgrade which gathers the views of clinicians from several countries. It has been developed under the newest international standards of assessment and analysis of the clinical management of the disease.

Consensus Clinical Management Guidelines (Full Text Only Available on the FARA Website)

User's Guide


Authors:
Executive committee: Professor Martin Delatycki, Dr Louise Corben, Professor Massimo Pandolfo, Professor David Lynch, Professor Jörg Shultz.

Contributing authors: Dr Laura Balcer (USA), Mr Ron Bartek (USA), Dr Claire Bates (UK), Ms Emma Campagna (Australia), Dr Louise Corben (Australia), Dr Miriam Cnop (Belgium), Professor Martin Delatycki (Australia), Professor Alexandra Dürr (France), Dr Anton Emmanuel (UK), Ms Jennifer Farmer (USA), Professor John Flynn (USA), Ms Lisa S. Friedman (USA), Dr Paola Giunti (UK), Dr Marios Hadjivassiliou (UK), Dr Michael Ho (Australia), Dr Grazia Isaya (USA), Dr Mary Kearney (Ireland), Ms Melissa Loucas (UK), Professor David R. Lynch (USA), Dr Caterina Marotti (Italy), Ms Sarah Milne (Australia), Dr Thierry Morlet (USA), Dr Andrew McGarry (USA), Professor Massimo Pandolfo (Belgium), Dr Jalesh Panicker (UK), Dr Michael Parkinson (UK), Dr R Mark Payne (USA), Dr Roger Peverill (Australia), Associate Professor Gary Rance (Australia), Ms Lucy Rodriguez (UK), Ms Kimberly A. Schadt (USA), Ms Lauren Seyer (USA), Professor Jörg Shultz (Germany), Dr S.H Subramony (USA), Dr. Kelly L. Sullivan (USA), Dr Adam Vogel (Australia), Dr Eppie Yiu (Australia), Dr Grace Yoon (Canada), Dr. Theresa A. Zesiewicz (USA).

Project: Increasing the expression of frataxin with the CRISPR system

Increasing the expression of frataxin with the CRISPR system. Mitacs (Mitacs is a national, not-for-profit organization that has designed and delivered research and training programs in Canada for 15 years) 2014

Intern: Noëlia Sanchez
Faculty Supervisor: Jacques Tremblay
Project Year: 2014
Province: Quebec
University: Université Laval & Canadian Association of Familial Ataxia
Partner: Feldan inc

Mammalian iron–sulphur proteins: novel insights into biogenesis and function

Mammalian iron–sulphur proteins: novel insights into biogenesis and function. Tracey A. Rouault; Nature Reviews Molecular Cell Biology (2014), doi:10.1038/nrm3909 published online 26 November 2014

Fe–S clusters are probably an unrecognized and elusive cofactor of many known proteins.

Transcription-Coupled Nucleotide Excision Repair Factors Promote R-Loop-Induced Genome Instability

Transcription-Coupled Nucleotide Excision Repair Factors Promote R-Loop-Induced Genome Instability. Pages Julie Sollier, Caroline Townsend Stork, María L. García-Rubio, Renee D. Paulsen, Andrés Aguilera, Karlene A. Cimprich; Molecular Cell, Available online 26 November 2014, DOI: http://dx.doi.org/10.1016/j.molcel.2014.10.020

An enzyme that fixes broken DNA sometimes destroys it instead

An enzyme that fixes broken DNA sometimes destroys it instead. Medicalxpress. November 26, 2014

"Recent work has also implicated these hybrids in neurodegenerative diseases, including Fragile X syndrome, Friedreich's ataxia and amyotrophic lateral sclerosis type 4," said Julie Sollier, PhD, the lead author of the paper and a postdoctoral researcher. "We would like to explore the potential role of the endonucleases we identified in these diseases as well."

Pain and itch in a dish: Scientists convert human skin cells into sensory neurons

Pain and itch in a dish: Scientists convert human skin cells into sensory neurons. ScienceDaily. www.sciencedaily.com/releases/2014/11/141125104338.htm (accessed November 26, 2014).

Source: The Scripps Research Institute

These neurons are also affected by spinal cord injury and involved in Friedreich's ataxia.


Journal Reference: Selective conversion of fibroblasts into peripheral sensory neurons. Joel W Blanchard, Kevin T Eade, Attila Szűcs, Valentina Lo Sardo, Rachel K Tsunemoto, Daniel Williams, Pietro Paolo Sanna, Kristin K Baldwin. Nature Neuroscience, 2014; DOI: 10.1038/nn.3887

Histone deacetylases (HDACs) and brain function

Histone deacetylases (HDACs) and brain function. Claude-Henry Volmar, Claes Wahlestedt, Neuroepigenetics, Available online 18 November 2014, ISSN 2214-7845, http://dx.doi.org/10.1016/j.nepig.2014.10.002.

Very little work has been done regarding the role of HDACs in neurologic disorders; however, a few studies show great promise. HDACs have been proposed as a target against the autosomal recessive neurodegenerative disorder Friedreich ataxia (FRDA)

Tangled web of interactions among proteins involved in iron-sulfur cluster assembly as unraveled by NMR, SAXS, chemical crosslinking, and functional studies

Tangled web of interactions among proteins involved in iron-sulfur cluster assembly as unraveled by NMR, SAXS, chemical crosslinking, and functional studies. Jin Hae Kim, Jameson R. Bothe, T. Reid Alderson, John L. Markley, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Available online 22 November 2014, ISSN 0167-4889, http://dx.doi.org/10.1016/j.bbamcr.2014.11.020.

FULL TEXT

Therapeutic strategies in mitochondrial disorders

Therapeutic strategies in mitochondrial disorders . Josef Finsterer, P.S. Bindu, Pediatric Neurology, Available online 15 November 2014, ISSN 0887-8994, http://dx.doi.org/10.1016/j.pediatrneurol.2014.06.023.

Despite the lack of a causal treatment for mitochondrial disorders, a nihilistic attitude towards the treatment issue is not justified. A number of studies are under way to search for causal approaches and highly effective symptomatic measures are available.

Coupling Transcriptional State to Large-Scale Repeat Expansions in Yeast

Coupling Transcriptional State to Large-Scale Repeat Expansions in Yeast . Kartik A. Shah, Ryan J. McGinty, Vera I. Egorova, Sergei M. Mirkin, Cell Reports, Available online 20 November 2014, ISSN 2211-1247, http://dx.doi.org/10.1016/j.celrep.2014.10.048.

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The Future of Neuroepigenetics in the Human Brain

The Future of Neuroepigenetics in the Human Brain. Amanda Mitchell, Panos Roussos, Cyril Peter, Nadejda Tsankova, Schahram Akbarian, Chapter Eight - In: Schahram Akbarian and Farah Lubin, Editor(s), Progress in Molecular Biology and Translational Science, Academic Press, 2014, Volume 128, Pages 199-228, ISSN 1877-1173, ISBN 9780128009772, http://dx.doi.org/10.1016/B978-0-12-800977-2.00008-5.

Imaging of Mitochondrial Dynamics in Motor and Sensory Axons of Living Mice

Imaging of Mitochondrial Dynamics in Motor and Sensory Axons of Living Mice. Irene Bolea, Wen-Biao Gan, Giovanni Manfedi, Jordi Magrané, n: Anne N. Murphy and David C. Chan, Editor(s), Methods in Enzymology, Academic Press, 2014, Volume 547, Pages 97-110, ISSN 0076-6879, ISBN 9780128014158, http://dx.doi.org/10.1016/B978-0-12-801415-8.00006-0.

Poor fluorodeoxyglucose uptake in myocardial viability study in nondiabetic Friedreich's ataxia patient.

Poor fluorodeoxyglucose uptake in myocardial viability study in nondiabetic Friedreich's ataxia patient. Patil S, Lele V., Indian J Nucl Med. 2014 Oct;29(4):262-3. doi: 10.4103/0972-3919.142638.

Computational analysis of evolutionary and structural aspects of Cryptochromes and Frataxins.

Computational analysis of evolutionary and structural aspects of Cryptochromes and Frataxins.[Ph.D. thesis], Tosatto, Silvio C E, University
of Padova, 31 January 2014.

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Dr. Susan Perlman appeared on American Health Journal Nov 7to discuss Friedreich’s Ataxia

Dr. Susan Perlman appeared on American Health Journal Nov 7 to discuss Friedreich’s Ataxia.  (the section about Friedreich’s Ataxia starts at 15:39)

Dr. Susan Perlman appeared on American Health Journal this Friday to discuss Friedreich’s Ataxia (FA) along with one of her patients, Stephanie Magness. They educated viewers on the clinical aspects of the disease as well as daily life and clinical studies.

Suppression of Enhanced Physiological Tremor via Stochastic Noise: Initial Observations

Suppression of Enhanced Physiological Tremor via Stochastic Noise: Initial Observations. Trenado C, Amtage F, Huethe F, Schulte-Mönting J, Mendez-Balbuena I, Stuart N. Baker, Mark Baker, Marie-Claude Hepp-Reymond, Elias Manjarrez, Rumyana Kristeva; PLoS ONE 9(11): e112782. doi:10.1371/journal.pone.0112782

OPEN ACCESS

Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron, and requirements for GTP, NADH, and ATP

Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron, and requirements for GTP, NADH, and ATP . Alok Pandey, Jayashree Pain, Arnab K. Ghosh, Andrew Dancis and Debkumar Pain; J. Biol. Chem. jbc.M114.610402. First Published on November 14, 2014, doi:10.1074/jbc.M114.610402

The experimental system as described here may help to define the biochemical basis of diseases that are associated with impaired Fe-S cluster biogenesis in mitochondria such as Friedreich's ataxia.

Mechanism Involved in the Blunted Anti-Oxidant Response in the Frataxin-Deficient Heart: Increased Nrf2 Degradation via both the Keap1 and GSK3β Pathway

Mechanism Involved in the Blunted Anti-Oxidant Response in the Frataxin-Deficient Heart: Increased Nrf2 Degradation via both the Keap1 and GSK3β Pathway. Amy Anzovino, Clare L. Hawkins, Michael L.H. Huang, Des R. Richardson; Free Radical Biology and Medicine, Volume 76, Supplement 1, November 2014, Page S46, ISSN 0891-5849, http://dx.doi.org/10.1016/j.freeradbiomed.2014.10.402.

Transforming Our Approach to Translational Neuroscience: The Role and Impact of Charitable Nonprofits in Research

Transforming Our Approach to Translational Neuroscience: The Role and Impact of Charitable Nonprofits in Research. Cynthia Joyce, Neuron, Volume 84, Issue 3, 5 November 2014, Pages 526-532, ISSN 0896-6273, http://dx.doi.org/10.1016/j.neuron.2014.10.030.

Friedreich Ataxia

Friedreich Ataxia. Massimo Pandolfo; Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease (Fifth Edition). 2015, Pages 833–843

Keywords: Ataxia; Cardiomyopathy; Chromatin; Histone acetylation; Induced pluripotent stem cells; Iron–sulfur clusters; Mitochondria, Iron; Neurodegenerative diseases; Oxidative stress; Transgenic mice; Triplet repeat expansion

NEW TOOL: ClinRegs, an online database of country-specific clinical research regulatory information

NEW: ClinRegs, an online database of country-specific clinical research regulatory information . The National Institutes of Health (NIH)

ClinRegs is an online database of country-specific clinical research regulatory information designed to save time and effort in planning and implementing clinical research.

When Lives Depend on Tech Transfer

When Lives Depend on Tech Transfer . IPWatchdog.com, Written by Joseph Allen, Allen & Associates.
Posted: Nov 3, 2014

Malfunctioning of the Iron–Sulfur Cluster Assembly Machinery in Saccharomyces cerevisiae Produces Oxidative Stress via an Iron-Dependent Mechanism, Causing Dysfunction in Respiratory Complexes

Malfunctioning of the Iron–Sulfur Cluster Assembly Machinery in Saccharomyces cerevisiae Produces Oxidative Stress via an Iron-Dependent Mechanism, Causing Dysfunction in Respiratory Complexes. Mauricio Gomez, Rocío V. Pérez-Gallardo, Luis A. Sánchez, Alma L. Díaz-Pérez, Christian Cortés-Rojo, Victor Meza Carmen, Alfredo Saavedra-Molina, Javier Lara-Romero, Sergio Jiménez-Sandoval, Francisco Rodríguez, José S. Rodríguez-Zavala, Jesús Campos-García. (2014)PLoS ONE 9(10): e111585. doi:10.1371/journal.pone.0111585

Charities’ role in supporting medical research

Charities’ role in supporting medical research. Times Higher Education, 16 October 2014

A group of medical charities spent more on health research last year than two government funding bodies, according to a report

Formation of [4Fe-4S] clusters in the mitochondrial iron-sulfur cluster assembly machinery

Formation of [4Fe-4S] clusters in the mitochondrial iron-sulfur cluster assembly machinery. Diego Brancaccio, Angelo Gallo, Maciej Mikolajczyk, Kairit Zovo, Peep Palumaa, Ettore Novellino, Mario Piccioli, Simone Ciofi-Baffoni, and Lucia Banci; Journal of the American Chemical Society Just Accepted Manuscript DOI: 10.1021/ja507822j

Treatment for speech disorder in Friedreich ataxia and other hereditary ataxia syndromes

Treatment for speech disorder in Friedreich ataxia and other hereditary ataxia syndromes. Vogel AP, Folker J, Poole ML; Cochrane Database of Systematic Reviews 2014, Issue 10. Art. No.: CD008953. DOI: 10.1002/14651858.CD008953.pub2

Review about the evidence about the effects of treatment on speech difficulties in people with Friedreich ataxia and other hereditary ataxias.

Fitting and verification of frequency modulation systems on children with normal hearing.

Fitting and verification of frequency modulation systems on children with normal hearing. Schafer, Erin C.; Bryant, Danielle; Sanders, Katie; Baldus, Nicole; Algier, Katherine; Lewis, Audrey; Traber, Jordan; Layden, Paige; Amin, Aneeqa; Source: Journal of the American Academy of Audiology, Volume 25, Number 6, June 2014, pp. 529-540(12)

Several recent investigations support the use of frequency modulation (FM) systems in children with normal hearing and auditory processing or listening disorders such as those diagnosed with auditory processing disorders, autism spectrum disorders, attention-deficit hyperactivity disorder, Friedreich ataxia, and dyslexia.

The Role of the Cerebellum in Cognition Beyond Coordination in the Central Nervous System

The Role of the Cerebellum in Cognition Beyond Coordination in the Central Nervous System; Maryam Noroozian, Volume 32, Issue 4, November 2014, Pages 1081–1104 DOI: 10.1016/j.ncl.2014.07.005

This article reviews in further detail the current understanding of cognitive deficits associated with cerebellar impairments and unravels its modulating role in cognitive and behavioral processes.

Neuro-ophthalmic Manifestations of Cerebellar Disease

Neuro-ophthalmic Manifestations of Cerebellar Disease; Shin C. Beh , Teresa C. Frohman , Elliot M. Frohman; Neurologic Clinics, Volume 32, Issue 4 DOI: 10.1016/j.ncl.2014.07.002

The cerebellum is responsible for refining ocular movements, thereby guaranteeing the best possible visual acuity and clarity despite changes in body or head positions or movement of the object of interest.

The Cerebellum and Sleep

The Cerebellum and Sleep; Lourdes M. DelRosso, Romy Hoque; Neurologic Clinics; Volume 32, Issue 4, November 2014, Pages 893–900 DOI: 10.1016/j.ncl.2014.07.003

Sleep medicine is an important and under-recognized part of the neurologic evaluation in those with cerebellar disease.

An AAV9 coding for frataxin clearly improved the symptoms and prolonged the life of Friedreich ataxia mouse models

An AAV9 coding for frataxin clearly improved the symptoms and prolonged the life of Friedreich ataxia mouse models. Catherine Gérard, Xiao Xiao, Mohammed Filali, Zoé Coulombe, Marie Arsenault, Jacques Couet, Juan Li, Marie-Claude Drolet, Pierre Chapdelaine, Amina Chikh & Jacques P Tremblay; Molecular Therapy — Methods & Clinical Development 1, Article number: 14044 ​doi:10.1038/mtm.2014.44

Article Open

Open-label pilot study of interferon gamma-1b in Friedreich ataxia

Open-label pilot study of interferon gamma-1b in Friedreich ataxia. L. Seyer, N. Greeley, D. Foerster, C. Strawser, S. Gelbard, Y. Dong, K. Schadt, M. G. Cotticelli, A. Brocht, J. Farmer, R. B. Wilson and D. R. Lynch; Acta Neurol Scand: DOI: 10.1111/ane.12337.

Conclusions – Interferon gamma-1b improved FARS scores without a clear relationship to changes in frataxin levels. Larger, longer placebo-controlled trials including biochemical assessments in affected tissues are necessary to evaluate fully the efficacy and utility of IFN-c in FRDA.

Probing the Kinetic Stabilities of Friedreich’s Ataxia Clinical Variants Using a Solid Phase GroEL Chaperonin Capture Platform

Probing the Kinetic Stabilities of Friedreich’s Ataxia Clinical Variants Using a Solid Phase GroEL Chaperonin Capture Platform. Ana R. Correia, Subhashchandra Naik, Mark T. Fisher and Cláudio M. Gomes; Biomolecules 2014, 4(4), 956-979; doi:10.3390/biom4040956

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FA & ACTIMMUNE Phase 2 Clinical Trial Results

FA & ACTIMMUNE Phase 2 Clinical Trial Results. Friedreich's Ataxia Analyst Day Presentation, Horizon Pharma plc, October 13, 2014

Clinical Potentials of Cardiomyocytes Derived from Patient-Specific Induced Pluripotent Stem Cells

Clinical Potentials of Cardiomyocytes Derived from Patient-Specific Induced Pluripotent Stem Cells. Kwong-Man Ng, Cheuk-Yiu Law and Hung-Fat Tse; J. Clin. Med. 2014, 3(4), 1105-1123; doi:10.3390/jcm3041105

OPEN ACCESS, FULL TEXT PDF

The cardiomyocytes derived from patients-specific iPSCs are of great potential in many clinical applications. This authentic human cardiomyocyte-based system is expected to compensate for the limitations of the current experimental animal models. This review provides detailed descriptions in the strategies and workflow of using the patient-specific iPSCs-derived cardiomyocytes in regenerative medicine, disease modeling and pharmacological applications. The examples illustrated in this review clearly evidenced the practical values of this novel technology. However, various limitations, such as the immaturities of iPSCs-derived cardiomyocytes, still need to be addressed, and future studies resolving these issues would be beneficial to the use of patient-specific iPSCs in clinical applications.

Horizon Pharma plc Reviews Future ACTIMMUNE® Opportunities at Analyst Day

Horizon Pharma plc Reviews Future ACTIMMUNE® Opportunities at Analyst Day. KING OF PRUSSIA, PA--(Marketwired - Oct 13, 2014)

SOURCE: Horizon Pharma plc

Cardiac Manifestations of Friedreich Ataxia

Cardiac Manifestations of Friedreich Ataxia. Hari Krishnan NAIR, Cardiology Boston Children's Hospital, Published on October 12, 2014

Cardiac Manifestations of Friedreich Ataxia from Hari Krishnan

The Diabetes Drug Target MitoNEET Governs a Novel Trafficking Pathway to Rebuild an Fe-S Cluster into Cytosolic Aconitase/Iron Regulatory Protein 1

The Diabetes Drug Target MitoNEET Governs a Novel Trafficking Pathway to Rebuild an Fe-S Cluster into Cytosolic Aconitase/Iron Regulatory Protein 1 . Ioana Ferecatu, Sergio Gonçalves, Marie-Pierre Golinelli-Cohen, Martin Clémancey, Alain Martelli, Sylvie Riquier, Eric Guittet, Jean-Marc Latour, Hélène Puccio, Jean-Claude Drapier, Ewen Lescop and Cécile Bouton; J. Biol. Chem. jbc.M114.548438. 2014, doi:10.1074/jbc.M114.548438

Horizon Pharma plc Announces Presentation of ACTIMMUNE(R) Phase 2 Data in Friedreich's Ataxia

Horizon Pharma plc Announces Presentation of ACTIMMUNE(R) Phase 2 Data in Friedreich's Ataxia. DUBLIN, IRELAND -- (Marketwired) -- 10/09/14

Positive Clinical Efficacy Signal Seen in Study of Twelve Patients; Company Planning Phase 3 Program

An abstract of the data has been published in a supplement to the Annals of Neurology and is being presented as a poster during the 139th Annual Meeting of the American Neurological Association in Baltimore, MD on Monday, October 13.

The roles of glutaredoxins ligating Fe–S clusters: Sensing, transfer or repair functions?

The roles of glutaredoxins ligating Fe–S clusters: Sensing, transfer or repair functions?; Jérémy Couturier, Jonathan Przybyla-Toscano, Thomas Roret, Claude Didierjean, Nicolas Rouhier, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Available online 28 September 2014, ISSN 0167-4889, http://dx.doi.org/10.1016/j.bbamcr.2014.09.018.

Trinucleotide expansion in disease: why is there a length threshold?

Trinucleotide expansion in disease: why is there a length threshold?. Do-Yup Lee, Cynthia T. McMurray; Current Opinion in Genetics & Development 2014, 26:131–140 DOI: http://dx.doi.org/10.1016/j.gde.2014.07.003

Horizon Pharma plc Receives Orphan-Drug Designation for ACTIMMUNE(R) (Interferon gamma-1b) in Friedreich's Ataxia

Horizon Pharma plc Receives Orphan-Drug Designation for ACTIMMUNE(R) (Interferon gamma-1b) in Friedreich's Ataxia. Oct 03, 2014 (Marketwired via COMTEX).

RTA 408 Capsules in Patients With Friedreich's Ataxia (MOXIe)

RTA 408 Capsules in Patients With Friedreich's Ataxia (MOXIe). A Phase 2 Study of the Safety, Efficacy, and Pharmacodynamics of RTA 408 in the Treatment of Friedreich's Ataxia (MOXIe). ClinicalTrials.gov Identifier: NCT02255435

Reata Announces the Initiation of Phase 2 Studies Examining RTA 408 for the Treatment of Friedreich's Ataxia and Mitochondrial Myopathies

Reata Announces the Initiation of Phase 2 Studies Examining RTA 408 for the Treatment of Friedreich's Ataxia and Mitochondrial Myopathies. -(Marketwired - September 30, 2014), SOURCE: Reata Pharmaceuticals, Inc.

The two initial Phase 2 trials will both be multi-center, double-blind, randomized, dose-ranging, placebo-controlled studies.

Comparing speech characteristics in spinocerebellar ataxias type 3 and type 6 with Friedreich ataxia

Comparing speech characteristics in spinocerebellar ataxias type 3 and type 6 with Friedreich ataxia. Bettina Brendel, Matthis Synofzik, Hermann Ackermann, Tobias Lindig, Theresa Schölderle, Ludger Schöls, Wolfram Ziegler; Journal of Neurology, September 2014. DOI 10.1007/s00415-014-7511-8

Idebenone and neuroprotection: antioxidant, pro-oxidant, or electron carrier?

Idebenone and neuroprotection: antioxidant, pro-oxidant, or electron carrier?. Sausan Jaber, Brian M. Polster; Journal of Bioenergetics and Biomembranes
September 2014 DOI 10.1007/s10863-014-9571-y

A Novel Mouse Model for Friedreich's Ataxia

A Novel Mouse Model for Friedreich's Ataxia. Inventors: Geschwind, Daniel H.; UCLA Office of Intellectual Property & Industry Sponsored Research

This new model exhibits various symptoms observed in FRDA patients, including cardiac atrophy, elevated iron-responsive proteins, neurodegeneration, motor neuropathy–and for the first time in an FRDA model–scoliosis and ataxia.

Next-Generation R&D Partnerships: The NCATS Success Story

Next-Generation R&D Partnerships: The NCATS Success Story , Information Technology and Innovation Foundation.

Free event on Wednesday, October 29, 2014,10:00 AM - 11:30 AM, Rayburn House Office Building 45 Independence Ave SW
(2168) Washington, DC20515

FGF8 Activates Proliferation and Migration in Mouse Post-Natal Oligodendrocyte Progenitor Cells

FGF8 Activates Proliferation and Migration in Mouse Post-Natal Oligodendrocyte Progenitor Cells . Pablo Cruz-Martinez, Almudena Martinez-Ferre, Jesus Jaramillo-Merchán, Alicia Estirado, Salvador Martinez, Jonathan Jones; PLoS ONE 9(9): e108241. doi:10.1371/journal.pone.0108241

Open Access, full text pdf

FA Dyclonine Study Review

FA Dyclonine Study Review. Posted: Sep 19 2014, By: Robert Dean

Understanding the frustration arising from the competition between function, misfolding, and aggregation in a globular protein.

Understanding the frustration arising from the competition between function, misfolding, and aggregation in a globular protein. Gianni S, Camilloni C, Giri R, Toto A, Bonetti D, Morrone A, Sormanni P, Brunori M, Vendruscolo M. Proc Natl Acad Sci U S A. 2014 Sep 16. pii: 201405233. [Epub ahead of print]

R2* mapping for brain iron: Associations with cognition in normal aging

R2* mapping for brain iron: Associations with cognition in normal aging; Christine Ghadery, Lukas Pirpamer, Edith Hofer, Christian Langkammer, Katja Petrovic, Marisa Loitfelder, Petra Schwingenschuh, Stephan Seiler, Marco Duering, Eric Jouvent, Helena Schmidt, Franz Fazekas, Jean-Francois Mangin, Hugues Chabriat, Martin Dichgans, Stefan Ropele, Reinhold Schmidt; Neurobiology of Aging, Available online 19 September 2014, ISSN 0197-4580, http://dx.doi.org/10.1016/j.neurobiolaging.2014.09.013.

We found the highest iron concentration in the globus pallidus, and pallidal as well as putaminal iron was significantly and inversely associated with cognitive performance in all cognitive domains, except memory. These associations were iron load-dependent. Vascular brain lesions and brain volume did not mediate the relationship between iron and cognitive performance.

Overlapping Binding Sites of the Frataxin Homologue Assembly Factor and the Heat Shock Protein 70 Transfer Factor on the Isu Iron-sulfur Cluster Scaffold Protein

Overlapping Binding Sites of the Frataxin Homologue Assembly Factor and the Heat Shock Protein 70 Transfer Factor on the Isu Iron-sulfur Cluster Scaffold Protein . Mateusz Manicki, Julia Majewska, Szymon Ciesielski, Brenda Schilke, Anna Blenska, Jacek Kominek, Jaroslaw Marszalek, Elizabeth A. Craig, and Rafal Dutkiewicz; J. Biol. Chem. jbc.M114.596726. First Published on September 16, 2014, doi:10.1074/jbc.M114.596726

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Iron-sulfur cluster biogenesis in mammalian cells: New insights into the molecular mechanisms of cluster delivery

Iron-sulfur cluster biogenesis in mammalian cells: New insights into the molecular mechanisms of cluster delivery. Nunziata Maio, Tracey.A. Rouault; Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Available online 19 September 2014, ISSN 0167-4889, http://dx.doi.org/10.1016/j.bbamcr.2014.09.009.

The tissue- specific phenotypes of FRDA might arise from the critical requirement of specific isoforms of FXN, which may be severely decreased in the disease. Interestingly, two rare frataxin isoforms have been recently identified [198], and their expression was substantially reduced in the heart (isoform III), and cerebellum (isoform II) of a FRDA patient, suggesting that novel expression patterns may explain some FRDA tissue specific phenotypes.

The role of iron in brain ageing and neurodegenerative disorders

The role of iron in brain ageing and neurodegenerative disorders. Roberta J Ward, Fabio A Zucca, Jeff H Duyn, Robert R Crichton, Luigi Zecca; The Lancet Neurology, Volume 13, Issue 10, October 2014, Pages 1045-1060, ISSN 1474-4422, http://dx.doi.org/10.1016/S1474-4422(14)70117-6.

Reimbursement of orphan drugs in Belgium: what (else) matters?

Reimbursement of orphan drugs in Belgium: what (else) matters?. Eline Picavet, David Cassiman and Steven Simoens; Orphanet Journal of Rare Diseases 2014, 9:139 doi:10.1186/s13023-014-0139-z

Excellent analysis of the problem, although the study focuses on the problem of orphan drugs in e Belgium, the findings can be extrapolated to most countries.

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The EMA will depend on the European Commissioner for Industry

New EU president moves regulation of medicines to industry department

Very disturbing news in Europe, The European Medicines Agency (EMA), the European equivalent of the FDA in USA, will depend on the European Commissioner for Industry. For European politicians, business are more important than the health of European citizens.

EN: New EU president moves regulation of medicines to industry department

ES: La EMA dependerá de la comisaría europea de Industria

Nasality in Friedreich ataxia

Nasality in Friedreich ataxia; Matthew L. Poole, Jessica S. Wee, Joanne E. Folker, Louise A. Corben, Martin B. Delatycki, Adam P. Vogel; Clinical Linguistics & Phonetics, Ahead of Print : Pages 1-13 (doi: 10.3109/02699206.2014.954734)

Keywords: Ataxia, dysarthria, hypernasality, hyponasality

Friedreich’s Ataxia: A Neuronal Point of View on the Oxidative Stress Hypothesis

Friedreich’s Ataxia: A Neuronal Point of View on the Oxidative Stress Hypothesis; Carletti, Barbara; Piemonte, Fiorella, Antioxidants 2014, 3, 592-603. doi:10.3390/antiox3030592 (registering DOI)

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Unexpected nerve neuroimaging findings in Friedreich’s ataxia

Unexpected nerve neuroimaging findings in Friedreich’s ataxia. Alessandro Salvalaggio, Mario Cacciavillani, Marta Lucchetta, Renzo Manara, Roberto Gasparotti, Chiara Briani; Clinical Neurophysiology, Available online 8 September 2014, ISSN 1388-2457, http://dx.doi.org/10.1016/j.clinph.2014.08.014.

Our findings may support a myelin involvement in the pathogenic mechanism of the FRDA associated neuropathy. The pathogenesis of axonal loss in FRDA is still not clear and both hypomyelination and slow axonal degeneration may play a role.

Cellular, Molecular and Functional Characterisation of YAC Transgenic Mouse Models of Friedreich Ataxia

Cellular, Molecular and Functional Characterisation of YAC Transgenic Mouse Models of Friedreich Ataxia .Anjomani Virmouni S, Sandi C, Al-Mahdawi S, Pook MA; PLoS ONE 9(9): e107416. doi:10.1371/journal.pone.0107416

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Screening for E3-Ubiquitin ligase inhibitors: challenges and opportunities

Screening for E3-Ubiquitin ligase inhibitors: challenges and opportunities. Vivien Landré, Barak Rotblat, Sonia Melino, Francesca Bernassola and Gerry Melino; Oncotarget, Published: September 03, 2014, Advance Publications

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Another interesting approach to inhibit ubiquitination of a specific substrate is to block the ubiquitination of the target rather than blocking the E3 ligase and therefore the ubiquitination of all its targets. This was demonstrated by a study that identified an inhibitor of the ubiquitination of frataxin, a mitochondrial protein whose downregulation is linked to Friedreich’s ataxia, a neuro-and cardiodegenerative disorder. Lavecchia et al.identified the ubiquitination site on frataxin and modelled the position of ubiquitin on the protein surface using in silico docking programs. Next, they used structure based virtual screening coupled with a cell-based assay of the 13 top hits, and identified a small molecule that disrupts the frataxin-ubiquitin interactions and thereby inhibits frataxin ubiquitination.

Edison's orphan drug (EPI-743) misses the mark in Phase II (Rett syndrome)

Edison's orphan drug (EPI-743) misses the mark in Phase II (Rett syndrome). FierceBiotech (Daily Biotech Industry Newsletter), September 4, 2014

Despite the setback, the biotech is still chugging along with mid-stage studies to chart EPI-743's potential in its lead indications, the rare CNS ailments Friedreich's ataxia and Leigh syndrome.

Muscle synergy stability and human balance maintenance

Muscle synergy stability and human balance maintenance. Tytus Wojtara, Fady Alnajjar, Shingo Shimoda and Hidenori Kimura; Journal of NeuroEngineering and Rehabilitation 2014, 11:129 doi:10.1186/1743-0003-11-129 Published: 30 August 2014

These results suggest that SSI can be used to quantitatively evaluate balance maintenance ability.

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Friedreich ataxia: New findings, new challenges

Friedreich ataxia: New findings, new challenges. David R. Lynch M.D., PhD and Lauren Seyer MS; Annals of Neurology, Accepted manuscript online: 27 AUG 2014 01:36AM EST | DOI: 10.1002/ana.24259

Scientists map the ‘editing marks’ on fly, worm, human genomes

Scientists map the ‘editing marks’ on fly, worm, human genomes. By Diana Lutz, NEWSROOM, Washington University in St. Louis. August 28, 2014

Comprehensive maps of these marks will allow them to test ways to safely restore marks altered by human disease

Epigenetic therapy for Friedreich's ataxia

Epigenetic therapy for Friedreich's ataxia;Elisabetta Soragni PhD, Wenyan Miao PhD, Marco Iudicello MD, David Jacoby MD, Stefania Demercanti M, Marinella Clerico MD, Filomena Longo MD, Antonio Piga MD, Sherman Ku PhD, Erica Campau BS, Jintang Du PhD, Pablo Penalver PhD1, Myriam Rai PhD Joseph C. Madara PhD, Kristopher Nazor PhD, Melinda O'Connor PhD, Anton Maximov PhD, Jeanne F. Loring PhD, Massimo Pandolfo MD, Luca Durelli MD, Joel M. Gottesfeld PhD and James R. Rusche PhD. Annals of Neurology, Accepted manuscript online: 27 AUG 2014 04:31AM EST | DOI: 10.1002/ana.24260

Processing of double-R-loops in (CAG)·(CTG) and C9orf72 (GGGGCC)·(GGCCCC) repeats causes instability.

Processing of double-R-loops in (CAG)·(CTG) and C9orf72 (GGGGCC)·(GGCCCC) repeats causes instability. Kaalak Reddy, Monika H.M. Schmidt, Jaimie M. Geist, Neha P. Thakkar, Gagan B. Panigrahi, Yuh-Hwa Wang and Christopher E. Pearson; Nucl. Acids Res. (2014) doi: 10.1093/nar/gku658 First published online: August 21, 2014

Open Access article distributed under the terms of the Creative Commons, FULL TEXT PDF

R-loops, transcriptionally-induced RNA:DNA hybrids, occurring at repeat tracts (CTG)n, (CAG)n, (CGG)n, (CCG)n and (GAA)n, are associated with diseases including myotonic dystrophy, Huntington's disease, fragile X and Friedreich's ataxia.

Cerebellum involvement in cortical sensorimotor circuits for the control of voluntary movements

Cerebellum involvement in cortical sensorimotor circuits for the control of voluntary movements. Rémi D Proville, Maria Spolidoro, Nicolas Guyon, Guillaume P Dugué, Fekrije Selimi, Philippe Isope, Daniela Popa & Clément Léna; Nature Neuroscience 17, 1233–1239 (2014) doi:10.1038/nn.3773

Towards Understanding RNA-Mediated Neurological Disorders

Towards Understanding RNA-Mediated Neurological Disorders. Ranhui Duan, Sumeet Sharma, Qiuping Xia, Kathryn Garber, Peng Jin; Journal of Genetics and Genomics, Available online 23 August 2014, ISSN 1673-8527, http://dx.doi.org/10.1016/j.jgg.2014.08.003.

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R loops are enriched over FXN intron 1 in cells with Friedreich ataxia-associated repeat expansions, compared to control cells. The formation of R loops precedes the presence of heterochromatin marks but correlates with epigenetic silencing of FXN and FMR1 and may be involved in the recruitment of enzymes involved in heterochromatinization.

Cerebellar pathology in Friedreich’s ataxia: Atrophied dentate nuclei with normal iron content

Cerebellar pathology in Friedreich’s ataxia: Atrophied dentate nuclei with normal iron content; K. Solbach, O. Kraff, M. Minnerop, A. Beck, L. Schöls, E.R. Gizewski, M.E. Ladd, D. Timmann; NeuroImage: Clinical, Available online 23 August 2014, ISSN 2213-1582, http://dx.doi.org/10.1016/j.nicl.2014.08.018.

Under a Creative Commons license, FULL TEXT PDF

Applying in vivo MRI methods we could demonstrate significant atrophy of the DN in the presence of normal iron content. The findings suggest that relaxation rates are not reliable biomarkers in clinical trials evaluating the potential effect of FA therapy.

Reaching tasks in an altered dynamic environment: Motor adaptation in FRDA patients

Reaching tasks in an altered dynamic environment: Motor adaptation in FRDA patients. (SIAMOC 2013 abstracts) M. Germanotta, M. Petrarca, S. Rossi, S. Carniel, E. Castelli, P. Cappa; Gait & Posture, Volume 40, Supplement 1, August 2014, Page S1, ISSN 0966-6362, http://dx.doi.org/10.1016/j.gaitpost.2014.05.018.

p53 directly regulates the transcription of the human frataxin gene and its lack of regulation in tumor cells decreases the utilization of mitochondrial iron

p53 directly regulates the transcription of the human frataxin gene and its lack of regulation in tumor cells decreases the utilization of mitochondrial iron. Rina Shimizu, Nguyen Ngoc Lan, Tran Tien Tai, Yuka Adachi, Asako Kawazoe, Anfeng Mu, Shigeru Taketani; Gene, Available online 23 August 2014, ISSN 0378-1119, http://dx.doi.org/10.1016/j.gene.2014.08.043.

Keywords: Frataxin; p53; Transcription; Heme biosynthesis; ALA; Cancerous cells

Study confirms close link between immune system and adult neurogenesis

Study confirms close link between immune system and adult neurogenesis. News Medical, Published on August 19, 2014.

these findings would stimulate a new area of research into immune therapies to target neurological diseases

More patients help drug companies pass valley of death - Indianapolis Business Journal

More patients help drug companies pass valley of death - Indianapolis Business Journal

But patient groups—especially those formed around rare and untreatable diseases—are indeed playing a crucial role in getting experimental drugs across the proverbial “valley of death”—where none of those deep-pocketed players want to put their money.

Intellect Neurosciences, Inc. Issues Letter to Shareholders - GlobeNewswire press release

Intellect Neurosciences, Inc. Issues Letter to Shareholders - GlobeNewswire press release

Shire is developing OX1 as a treatment for Friedreich's Ataxia and possibly other diseases for which OX1 may qualify for orphan drug designation.

Grant Alert: Hematopoietic Stem Cell-Based Therapy For Friedrich Ataxia (University Of California San Diego, La Jolla, United States)

Grant Alert: Hematopoietic Stem Cell-Based Therapy For Friedrich Ataxia (University Of California San Diego, La Jolla, United States). Project Leader: CHERQUI, STEPHANIE

The role of iron in neurodegenerative disorders: insights and opportunities with synchrotron light

The role of iron in neurodegenerative disorders: insights and opportunities with synchrotron light. Collingwood Joanna Frances, Davidson Mark Rogers, Front. Pharmacol., 19 August 2014 | doi: 10.3389/fphar.2014.00191

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Preimplantation genetic diagnosis for inherited neurological disorders

Preimplantation genetic diagnosis for inherited neurological disorders. Ilan Tur-Kaspa, Roohi Jeelani
& P. Murali Doraiswamy, Nature Reviews Neurology 10, 417–424 (2014), doi:10.1038/nrneurol.2014.84

Preimplantation genetic diagnosis (PGD) is an option for couples at risk of having offspring with an inherited debilitating or fatal neurological disorder who wish to conceive a healthy child.

The influence of the European paediatric regulation on marketing authorisation of orphan drugs for children

The influence of the European paediatric regulation on marketing authorisation of orphan drugs for children. Annemarie Rosan Kreeftmeijer-Vegter, Anthonius de Boer, Roselinda H van der Vlugt-Meijer and Peter J de Vries; Orphanet Journal of Rare Diseases 2014, 9:120 doi:10.1186/s13023-014-0120-x

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STATegics has identified CNS-available small molecule erythropoietin (EPO) Allomimetics that selectively activate the tissue-protective EPO receptor

STATegics has identified CNS-available small molecule erythropoietin (EPO) Allomimetics that selectively activate the
tissue-protective EPO receptor .

The compounds also demonstrate a favorable safety profile and penetrance to the brain at pharmacologically relevant concentrations, and are being investigated for treatment of PD, Friedreich’s ataxia, and acute kidney injury.

Electrochemical impedance sensor based on small molecule modified Au electrode for the recognition of a trinucleotide repeats

Electrochemical impedance sensor based on small molecule modified Au electrode for the recognition of a trinucleotide repeats .
Hanping He, Xiaoqian Peng, Min Huang, Gang Chang, Xiuhua Zhang and Shengfu Wang; Analyst, 2014, Accepted Manuscript,
DOI: 10.1039/C4AN00853G; Received 12 May 2014, Accepted 10 Aug 2014

The electrochemical impedance sensor provides the simple and rapid method to detect trinucleotide repeats without requiring labelling and immobilizations of DNA, making it promising for the early diagnosis of the neurodegenerative diseases

Deferiprone in Friedreich’s Ataxia: A six-month randomized controlled trial

Deferiprone in Friedreich’s Ataxia: A six-month randomized controlled trial. Massimo Pandolfo, Javier Arpa, Martin B. Delatycki, Kim Hanh Le Quan Sang, Caterina Mariotti, Arnold Munnich, Irene Sanz-Gallego, Geneieve Tai, Mark A. Tarnopolsky, Franco Taroni, Michael Spino and Fernando Tricta; Annals of Neurology, DOI: 10.1002/ana.24248. Accepted manuscript online: 11 AUG 2014 09:41AM EST | DOI: 10.1002/ana.24248

A study of up to 12 years of follow-up of Friedreich ataxia utilising four measurement tools

A study of up to 12 years of follow-up of Friedreich ataxia utilising four measurement tools. Geneieve Tai, Louise A Corben, Lyle Gurrin, Eppie M Yiu, Andrew Churchyard, Michael Fahey, Brian Hoare, Sharon Downie, Martin B Delatycki; J Neurol Neurosurg Psychiatry jnnp-2014-308022Published Online First: 11 August 2014 doi:10.1136/jnnp-2014-308022

Epigenetic promoter silencing in Friedreich ataxia is dependent on repeat length

Epigenetic promoter silencing in Friedreich ataxia is dependent on repeat length. Yogesh K. Chutake, Christina Lam, Whitney N. Costello, Michael Anderson and Sanjay I. Bidichandani; Ann Neurol. http://dx.doi.org/10.1002/ana.24249; 2014

Dyclonine rescues frataxin deficiency in animal models and buccal cells of patients with Friedreich's Ataxia

Dyclonine rescues frataxin deficiency in animal models and buccal cells of patients with Friedreich's Ataxia. Sunil Sahdeo, Brian Scott, Marissa McMackin, Mittal Jasoliya, Brandon Brown2, Heike Wulff, Sue Perlman, Mark Pook and Gino Cortopassi; Hum. Mol. Genet. (2014) doi: 10.1093/hmg/ddu408 First published online: August 11, 2014

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Monitoring mood states in everyday life: A new device for patients with cerebellar ataxia

Monitoring mood states in everyday life: A new device for patients with cerebellar ataxia, Silvia Clausi, Fabio Aloise, Maria P. Contento, Luigi Pizzamiglio, Marco Molinari, Maria Leggio; Psychiatry Research, Available online 1 August 2014, ISSN 0165-1781, http://dx.doi.org/10.1016/j.psychres.2014.07.051.


The preliminary data underscore the necessity to implement specific instruments to examine mood disorders in neurological patients. The MoMo device may be extremely valuable in clinical practice, allowing physicians to evaluate daily and weekly mood fluctuations during rehabilitation, pharmacological therapy, and psychotherapy, particularly in neurological patients.

AmorChem, Université Laval and CHU de Québec to collaborate on Friedreich’s Ataxia project

AmorChem, Université Laval and CHU de Québec to collaborate on Friedreich’s Ataxia project. by Biotechnology Focus • August 5, 2014 • Orphan drugs, Science Focus

Frataxin deficiency increases cyclooxygenase 2 and prostaglandins in cell and animal models of Friedreich's ataxia

Frataxin deficiency increases cyclooxygenase 2 and prostaglandins in cell and animal models of Friedreich's ataxia. Genki Hayashi, Yan Shen, Theresa L. Pedersen, John W. Newman, Mark Pook and Gino Cortopassi; Hum. Mol. Genet. (2014) doi: 10.1093/hmg/ddu407 First published online: August 7, 2014

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Medical management of hereditary optic neuropathies

Medical management of hereditary optic neuropathies. La Morgia C, Carbonelli M, Barboni P, Sadun AA and Carelli V; Front. Neurol. 5:141. doi: 10.3389/fneur.2014.00141

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Hypertrophic cardiomyopathy: a heart in need of an energy bar?

Hypertrophic cardiomyopathy: a heart in need of an energy bar?. Styliani Vakrou and M Roselle Abraham; Front. Physiol. 5:309. doi: 10.3389/fphys.2014.00309

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Mesenchymal Stem Cells Improve Motor Functions and Decrease Neurodegeneration in Ataxic Mice

Mesenchymal Stem Cells Improve Motor Functions and Decrease Neurodegeneration in Ataxic Mice. Jonathan Jones, Alicia Estirado, Carolina Redondo, Jesus Pacheco-Torres, Maria-Salomé Sirerol-Piquer, José Manuel Garcia-Verdugo and Salvador Martinez; Molecular Therapy accepted article preview 29 July 2014; doi: 10.1038/mt.2014.143

Bone marrow mesenchymal stem cell transplantation, both autologous and allogeneic, is a feasible therapeutic option to consider in delaying the neurodegeneration observed in the dorsal root ganglia of Friedreich´s ataxia patients.

Hierarchical Virtual Screening Approaches in Small Molecule Drug Discovery

Hierarchical Virtual Screening Approaches in Small Molecule Drug Discovery. Ashutosh Kumar, Kam Y.J. Zhang,Methods, Available online 27 July 2014, ISSN 1046-2023, http://dx.doi.org/10.1016/j.ymeth.2014.07.007.

Several virtual screening studies are discussed to demonstrate the successful application of hierarchical virtual screening in small molecule drug discovery. Scaffold searches identified a series of compounds able to disrupt frataxin/ubiquitin PPI, resulted in the identification of one compound that prevented frataxin ubiquitination and degradation.

Clinical and Genetic Study of Friedreich’s Ataxia and Ataxia with Vitamin E Deficiency in 44 Moroccan Families

Clinical and Genetic Study of Friedreich’s Ataxia and Ataxia with Vitamin E Deficiency in 44 Moroccan Families. Fatima Imounan, Naima Bouslam, El Hachmia Aitbenhaddou1, Wafa Regragui1, Ahmed Bouhouche, Ali Benomar, Mohammed Yahyaoui; World Journal of Neuroscience, 2014, 4, 299-305, Published Online August 2014 in SciRes. http://www.scirp.org/journal/wjns
http://dx.doi.org/10.4236/wjns.2014.44033

Autosomal Recessive Cerebellar Ataxias

Autosomal Recessive Cerebellar Ataxias; Dr. Anne Noreau, Dr. Nicolas Dupré, Dr. Jean-Pierre Bouchard, Dr. Patrick A. Dion, Dr. Guy A. Rouleau; Handbook of the Cerebellum and Cerebellar Disorders, 2013, pp 2177-2191

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Prise en charge pluridisciplinaire des déformations du tronc chez l’enfant et l’adolescent polyhandicapé

Prise en charge pluridisciplinaire des déformations du tronc chez l’enfant et l’adolescent polyhandicapé; R. Vialle, A. Dubory, H. Bouloussa, P. Mary, S. Zakine; Archives de Pédiatrie, Volume 21, Issue 5, Supplement 1, May 2014, Pages 149-150, ISSN 0929-693X, http://dx.doi.org/10.1016/S0929-693X(14)71505-2.

Prévalence des scolioses dans l'Ataxie de Friedreich 80%. L’amélioration des techniques chirurgicales, mais d’abord et avant tout réanimatoires, pneumologiques, cardiologiques et anesthésiques, permet de proposer des solutions chirurgicales plus ou moins complexes à un très grand nombre de patients, y compris les plus fragiles.

New results ease previous concerns that gene-editing techniques could add unwanted mutations to stem cells

New results ease previous concerns that gene-editing techniques could add unwanted mutations to stem cells. Medicalnewstoday, Sunday 13 July 2014

The iPSC could be much more than a tool for research, wait and see ...

The researcher says: "doesn't necessarily mean that there are no inherent risks to using stem cells with edited genes, but that the editing process doesn't make the stem cells any less safe."

AVANCES EN EL TRATAMIENTO DE LAS ATAXIAS CRÓNICAS-Therapeutic developments in chronic ataxias

AVANCES EN EL TRATAMIENTO DE LAS ATAXIAS CRÓNICAS-Therapeutic developments in chronic ataxias. Buompadre MC.; Medicina (B Aires). 2013;73 Suppl 1:49-54.

Palabras clave: ataxia cerebelosa, tratamiento, agentes antioxidantes, corticoides, vitamina

KEYWORDS: antioxidant agents; cerebellar ataxia; corticosteroid; treatment; vitamin

[Article in Spanish]

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Genes and Genetic Testing in Hereditary Ataxias

Genes and Genetic Testing in Hereditary Ataxias. Sandford, E.; Burmeister, M.; Genes. 2014; 5(3):586-603.

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Therapeutic approaches for the treatment of Friedreich’s ataxia

Therapeutic approaches for the treatment of Friedreich’s ataxia, Cassandra J Strawser, Kimberly A Schadt, David R Lynch, 2014, Ahead of Print : Pages 1-9 (doi: 10.1586/14737175.2014.939173)

Keywords: coenzyme Q10, deferiprone, EPI-743, EPO, Friedreich ataxia, gene therapy, idebenone, mitochondrial dysfunction, tat-frataxin

Sleep and sleep disorders in rare hereditary diseases: a reminder for the pediatrician, pediatric and adult neurologist, general practitioner, and sleep specialist

Sleep and sleep disorders in rare hereditary diseases: a reminder for the pediatrician, pediatric and adult neurologist, general practitioner, and sleep specialist. Review article, Natan Gadoth and imageArie Oksenberg, Front. Neurol., 17 July 2014 | doi: 10.3389/fneur.2014.00133

The authors suggest that snoring and obstructive sleep apnea (OSA) in FRDA is related to disease duration and the presence of reduced respiratory muscle strength in conjunction with scoliosis and poor posture.

Sensitivity of Spatiotemporal Gait Parameters in Measuring Disease Severity in Friedreich Ataxia

Sensitivity of Spatiotemporal Gait Parameters in Measuring Disease Severity in Friedreich Ataxia. Sarah C. Milne, Darren R. Hocking, Nellie Georgiou-Karistianis, Anna Murphy, Martin B. Delatycki, Louise A. Corben; The Cerebellum July 2014

Spatiotemporal gait parameters are a sensitive measure of gait decline in individuals with FRDA and should be considered for inclusion in intervention studies whilst participants are still ambulant.

Coexistence of tuberous sclerosis and Friedreich ataxia

Coexistence of tuberous sclerosis and Friedreich ataxia. Melanie Walker, Ali Samii, Thomas Bird; Journal of the Neurological Sciences Volume 221, Issue 1 , Pages 91-93, 15 June 2004

"The occurrence of two mutations on the same chromosome is probably coincidental but emphasizes the importance of searching for additional genetic causes when the phenotype does not fit with an established genetic diagnosis."

Engineering synthetic TALE and CRISPR/Cas9 transcription factors for regulating gene expression

Engineering synthetic TALE and CRISPR/Cas9 transcription factors for regulating gene expression. Ami M. Kabadi, Charles A. Gersbach, Available online 8 July 2014, ISSN 1046-2023, http://dx.doi.org/10.1016/j.ymeth.2014.06.014.
(http://www.sciencedirect.com/science/article/pii/S1046202314002369)

There is a long way to go, perhaps too long, but opens up a world of opportunity to cure genetic diseases.

NIH Grant: THE ROLE OF ACETYLATION IN THE REGULATION IRON-SULFUR CLUSTER BIOGENESIS AND MITO

NIH Grant: THE ROLE OF ACETYLATION IN THE REGULATION IRON-SULFUR CLUSTER BIOGENESIS AND MITO.

Source: NIH Grant #8721002 (DUKE UNIVERSITY, DURHAM, UNITED STATES)
Organisation: DUKE UNIVERSITY, DURHAM, UNITED STATES

Functional Characterization of Friedreich Ataxia iPS-Derived Neuronal Progenitors and Their Integration in the Adult Brain

Functional Characterization of Friedreich Ataxia iPS-Derived Neuronal Progenitors and Their Integration in the Adult Brain . Matthew J. Bird, Karina Needham, Ann E. Frazier, Jorien van Rooijen, Jessie Leung, Shelley Hough, Mark Denham, Matthew E. Thornton, Clare L. Parish, Bryony A. Nayagam, Martin Pera, David R. Thorburn, Lachlan H. Thompson, Mirella Dottori. PLoS ONE 9(7): e101718. doi:10.1371/journal.pone.0101718, Published: July 7, 2014

FA iPS cells are highly valuable for establishing a human cellular model system of FRDA that can be further utilised to accelerate development of FRDA treatments.

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Patent alert: Treatment Of FrataxinRelated Diseases By Inhibition Of Natural Antisense Transcript To Fxn

Patend Alert: Treatment Of FrataxinRelated Diseases By Inhibition Of Natural Antisense Transcript To Fxn. Inventor(s): COLLARD JOSEPH [US]; SHERMAN OLGA KHORKOVA [US]; Applicant(s): CURNA INC [US] +

The role of frataxin in fission yeast iron metabolism: Implications for Friedreich’s ataxia

The role of frataxin in fission yeast iron metabolism: Implications for Friedreich’s ataxia. Yu Wang, Yiwei Wang, S. Marcus, L.S. Busenlehner; Biochimica et Biophysica Acta (BBA) - General Subjects, Available online 3 July 2014, ISSN 0304-4165, http://dx.doi.org/10.1016/j.bbagen.2014.06.017

This paper provide evidence that suggests dysregulated Fe-S cluster biogenesis is a primary effect of both frataxin overexpression and deficiency as in Friedreich’s ataxia, it also suggests that therapies to increase transcription and translation of endogenous frataxin or to replace exogenous frataxin via gene therapy, must tightly control protein expression since high levels of frataxin are detrimental to the cell in a manner similar to its deficiency.

Preliminary Study of the Scale To Assess Ataxia and Neurologic Dysfunction (STAND)

Preliminary Study of the Scale To Assess Ataxia and Neurologic Dysfunction (STAND). Sponsor: University of South Florida; ClinicalTrials.gov identifier: NCT02179333, First received: June 27, 2014

Subjects with Ataxia, Patients with a diagnosis of ataxia (Friedreich's ataxia or Spinocerebellar ataxia type 1-30) aged 18-80 years old will be recruited for the study.

Biomarkers for Mitochondrial Diseases Emerging

Biomarkers for Mitochondrial Diseases Emergin,  CHOP, Friedreich’s Ataxia Center of Excellence, by Research Communications, Jul 01 2014

Nuevas aproximaciones terapéticas para el tratamiento de la Ataxia de Friedreich: HBSP y BDNF

Nuevas aproximaciones terapéticas para el tratamiento de la Ataxia de Friedreich: HBSP y BDNF; Autor (es): Katsu Jiménez, Yurika María; Director (es): Díaz Nido, Javier (dir.) Tesis doctoral inédita, leída en Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 15/07/2013

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Joint preserving surgery versus arthrodesis in operative treatment of patients with neuromuscular polyneuropathy: questionnaire assessment.

Joint preserving surgery versus arthrodesis in operative treatment of patients with neuromuscular polyneuropathy: questionnaire assessment. Marek Napiontek,
Krzysztof Pietrzak; European Journal of Orthopaedic Surgery & Traumatology, June 2014, DOI 10.1007/s00590-014-1498-9

Keywords: Foot, Paralytic deformity, Charcot–Marie–Tooth disease, Friedreich ataxia, Neuromuscular polyneuropathy

The results show that none of the surgical techniques used for correction of foot deformities in motor-sensory polyneuropathies seems to be preferable.

MutLα Heterodimers Modify the Molecular Phenotype of Friedreich Ataxia

MutLα Heterodimers Modify the Molecular Phenotype of Friedreich Ataxia . Ezzatizadeh V, Sandi C, Sandi M, Anjomani-Virmouni S, Al-Mahdawi S, Pook MA., PLoS ONE 9(6): e100523. doi:10.1371/journal.pone.0100523

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Human frataxin activates Fe-S cluster biosynthesis by facilitating sulfur transfer chemistry

Human frataxin activates Fe-S cluster biosynthesis by facilitating sulfur transfer chemistry. Jennifer Bridwell-Rabb, Nicholas G. Fox, Chi-Lin Tsai, Andrew M Winn, and David P. Barondeau. Biochemistry Just Accepted Manuscript. DOI: 10.1021/bi500532e Publication Date (Web): June 27, 2014

Lanzaderas y terapia génica contra la ataxia de Friedreich

Lanzaderas y terapia génica contra la ataxia de Friedreich .“excelenciencia.org”. 19/06/2014

"Si se cumplen las previsiones, apunta Teixidó, antes de las próximas navidades la tecnología resultante de esta unión debería verificarse en modelos animales e iniciar el camino de investigación preclínica que finalmente desemboque en un eventual ensayo clínico."

La unión de los dos centros de investigación y la capacidad de la plataforma permitieron desarrollar un sólido proyecto que atrajo la atención de la estadounidense The Friedreich's Ataxia Research Alliance (FARA), http://www.curefa.org/ de gran potencia organizativa y, sobre todo, económica.

Corneal Sensitivity and Tear Function in Neurodegenerative Diseases.

Corneal Sensitivity and Tear Function in Neurodegenerative Diseases. Ornek N, Dağ E, Ornek K; Current eye Research [2014:1-6]

FA patients did not show any abnormalities in either outcome measures, Corneal sensitivity measured using a Cochet-Bonnet esthesiometer and Tear function tests which included tear break-up time (TBUT) and Schirmer's. This may be attributed to, unlike other Neurodegenerative Diseases, lack of autonomic disturbances in FA patients

Powerhouse down: Complex II dissociation in the respiratory chain

Powerhouse down: Complex II dissociation in the respiratory chain. Hwang MS, Rohlena J, Dong LF, Neuzil J, Grimm S., Mitochondrion (2014), http://dx.doi.org/10.1016/j.mito.2014.06.001

KEYWORDS: apoptosis; complex II; mitochondria; iron sulfur clusters.

From mice to men: lessons from mutant ataxic mice

From mice to men: lessons from mutant ataxic mice. Jan Cendelin, Cerebellum & Ataxias 2014 1:4, doi:10.1186/2053-8871-1-4

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Quantitative proteomic analysis identifies targets and pathways of a 2-aminobenzamide HDAC inhibitor in Friedreich’s Ataxia Patient iPSC derived Neural Stem Cells

Quantitative proteomic analysis identifies targets and pathways of a 2-aminobenzamide HDAC inhibitor in Friedreich’s Ataxia Patient iPSC derived Neural Stem Cells. Bing Shan, Chunping Xu, Yaoyang Zhang, Tao Xu, Joel Gottesfeld, and John R. Yates; J. Proteome Res., Just Accepted Manuscript, DOI: 10.1021/pr500514r, Publication Date (Web): June 16, 2014

Brush strokes only can reveal it? Defining certain ultra-structural alterations in hairs of Friedreich’s Ataxia patients as a promising pre-diagnostic approach

Brush strokes only can reveal it? Defining certain ultra-structural alterations in hairs of Friedreich’s Ataxia patients as a promising pre-diagnostic approach. F. Pinar Turkmenoglu, U. Baran Kasirga; Abstracts of IFAA Congress, Annals of Anatomy - Anatomischer Anzeiger, Volume 196, Supplement, August 2014, Pages 1-286, ISSN 0940-9602, http://dx.doi.org/10.1016/j.aanat.2014.05.035.

In a scanning electron microscope examination ultra-structural hair alterations were differentiated by the time along with increasing neurologic symptoms, perhaps can be considered a pre-diagnostic tool for FRDA.

HSOP's Mouli Wins Most Outstanding At Auburn's Research Week

HSOP's Mouli Wins Most Outstanding At Auburn's Research Week. The Auburn pharmacist e-news, Auburn University. June 12, 2014

Currently she is developing novel drug strategies for increasing the transcriptional regulation of frataxin to mitigate the detrimental effects of Doxorubicin upon frataxin.

The Alteration of the C-terminal Region of Human Frataxin Distorts its Structural Dynamics and Function

The Alteration of the C-terminal Region of Human Frataxin Distorts its Structural Dynamics and Function. Santiago E. Faraj, Ernesto A. Roman, Martin Aran, Mariana Gallo and Javier Santos; FEBS Journal, Accepted manuscript online: 12 JUN 2014, DOI: 10.1111/febs.12869

In 5% of patients the typical GAA expansion is present in only one fxn allele and a missense mutation is found in the other allele. the disease course in these patients can be as severe as for patients with two expanded alleles.

The Alteration of the C-terminal Region of Human Frataxin Distorts its Structural Dynamics and Function in L198R mutant, or its complete truncation in FXN 81-193 causes FRDA.

SIRT3 regulates cellular iron metabolism and cancer growth by repressing iron regulatory protein 1

SIRT3 regulates cellular iron metabolism and cancer growth by repressing iron regulatory protein 1; S M Jeong, J Lee, L W S Finley, P J Schmidt, M D Fleming and M C Haigis; Oncogene advance online publication 9 June 2014; doi: 10.1038/onc.2014.124

The activity of SIRT3 is inhibited in frataxin-deficient heart, it may contribute to the cardiomyopathy in Friedreich’s ataxia. Friedreich’s ataxia cells exhibit an increased IRP1 activity and iron accumulation, thus, it will be interesting for future studies to examine the role of SIRT3 in systemic iron homeostasis and iron-related human diseases.

Autologous Stem Cell Transplant with Gene Therapy for Friedreich Ataxia

Autologous Stem Cell Transplant with Gene Therapy for Friedreich Ataxia; P.T. Naoki Tajiri, B.S. Meaghan Staples, Yuji Kaneko, Seung U. Kim, Theresa A. Zesiewic, Cesar V. Borlongan, Medical Hypotheses, Available online 9 June 2014, ISSN 0306-9877, http://dx.doi.org/10.1016/j.mehy.2014.05.022.

HDAC Inhibition Appears Safe in Early Trial on Friedreich's Ataxia

HDAC Inhibition Appears Safe in Early Trial on Friedreich's Ataxia, NEWS FROM THE AAN ANNUAL MEETING. Neurology Today:
5 June 2014 - Volume 14 - Issue 11 - p 46-47, doi: 10.1097/01.NT.0000451003.10471.a7

In a phase 1 trial, a histone deacetylase inhibitor appears to be safe and to increase expression of the frataxin gene in adult patients with Friedreich's ataxia.

Antioxidant targeting by deferiprone in diseases related to oxidative damage

Antioxidant targeting by deferiprone in diseases related to oxidative damage . Kontoghiorghe CN, Kolnagou A, Kontoghiorghes GJ.; Front Biosci (Landmark Ed). 2014 Jun 1;19:862-885. http://dx.doi.org/10.2741/4253

Keywords:antioxidant pharmaceuticals, free radical damage (FRD), Deferiprone (L1), iron overload, cardiomyopathy, acute kidney disease, Friedreich ataxia.

Myelin paucity of the superior cerebellar peduncle in individuals with Friedreich ataxia: an MRI magnetization transfer imaging study

Myelin paucity of the superior cerebellar peduncle in individuals with Friedreich ataxia: an MRI magnetization transfer imaging study. Louise A. Corben, Saman Rassaei Kashuk, Hamed Akhlaghi, Sharna Jamadar, Martin B. Delatycki, Joanne Fielding, Beth Johnson, Nellie Georgiou-Karistianis, Gary F. Egan, Journal of the Neurological Sciences, Available online 1 June 2014, ISSN 0022-510X, http://dx.doi.org/10.1016/j.jns.2014.05.057.

This is the first study to demonstrate reduced MTR in the SCP of individuals with FRDA when compared to control participants. These findings may reflect a process of disruption of the reciprocal relationship between oligodendrocytes and axons resulting in paucity of myelin, and provides significant new insight into the neurodegenerative pathology of FRDA

Photoinduced Transformation of Iron Chelator Deferiprone: Possible Implications in Drug Metabolism and Toxicity

Photoinduced Transformation of Iron Chelator Deferiprone: Possible Implications in Drug Metabolism and Toxicity. V.A. Timoshnikov, V.I. Klimentiev, N.E. Polyakov, G.J. Kontoghiorghes, Journal of Photochemistry and Photobiology A: Chemistry, Available online 2 June 2014, ISSN 1010-6030, http://dx.doi.org/10.1016/j.jphotochem.2014.05.012.

Thefindings suggest that high dose of sunlight might cause chemical modifications which may have chemical, biochemical, pharmacological and toxicological implications, especially possible undesirable phototoxic effects in patients undergoing treatment in countries with increased sunlight exposure.

C9orf72; abnormal RNA expression is the key

C9orf72; abnormal RNA expression is the key. Peter Heutink, Iris E. Jansen, Emily M. Lynes, Experimental Neurology, Available online 27 May 2014, ISSN 0014-4886, http://dx.doi.org/10.1016/j.expneurol.2014.05.020.

Despite differences with Friedreich's ataxia, hexanucleotide repeat instead of trinucleotide repeat...., it could be many points in common with the FA, as the loss of protein expression and toxic RNA species. It is interesting the authors's hypothesis about the mechanisms leading to pathology.

Low Bone Mineral Density in Friedreich Ataxia.

Low Bone Mineral Density in Friedreich Ataxia. Eigentler A1, Nachbauer W, Donnemiller E, Poewe W, Gasser RW, Boesch S.; Cerebellum. 2014 May 25. [Epub ahead of print]

Managing Dysphagia Through Diet Modifications

Managing Dysphagia Through Diet Modifications. Garcia, Jane Mertz PhD, CCC-SLP; Chambers, Edgar IV PhD; AJN, American Journal of Nursing: November 2010 - Volume 110 - Issue 11 - pp 26-33; doi: 10.1097/01.NAJ.0000390519.83887.02

Keywords: dysphagia, impaired swallowing, dietary modification, malnutrition, aspiration pneumonia

Tissue specificity in DNA repair: lessons from trinucleotide repeat instability

Tissue specificity in DNA repair: lessons from trinucleotide repeat instability. Vincent Dion; Trends in Genetics, Available online 16 May 2014, ISSN 0168-9525, http://dx.doi.org/10.1016/j.tig.2014.04.005.

Keywords: DNA repair; genome stability; trinucleotide repeat instability; base excision repair; single-strand break repair; nucleotide excision repair; tissue-specific DNA repair

Gene therapy protects heart in Friedreich's ataxia

Gene therapy protects heart in Friedreich's ataxia. Alexandra Flemming; Nature Reviews Drug Discovery (2014); doi:10.1038/nrd4346; Published online 23 May 2014

Herzbeteiligung bei Friedreich-Ataxie / Heart involvement in Friedreich's ataxia.

Herzbeteiligung bei Friedreich-Ataxie / Heart involvement in Friedreich's ataxia. Weidemann F, Scholz F, Florescu C, Liu D, Hu K, Herrmann S, Ertl G, Störk S.; Herz. 2014 May 23. DOI 10.1007/s00059-014-4097-y

[Article in German]

Keywords: Mitochondriale Funktion, Pathophysiologie, Frataxin, Kardiomyopathie, Herzinsuffizienz, Mitochondrial function, Pathophysiology, Frataxin, Cardiomyopathy, Heart failure

Spécificités de la prise en charge anesthésique chez les patients souffrant de maladie neurologique : éclairage sur l’anesthésie locorégionale/Anaesthetic management of patient with neurological disease: Focus on regional anaesthesia

Spécificités de la prise en charge anesthésique chez les patients souffrant de maladie neurologique : éclairage sur l’anesthésie locorégionale; Jean-Marc Malinovsky, Armine Hamidi, Chantal Lelarge, Catherine Boulay-Malinovsky, La Presse Médicale, Available online 20 May 2014, ISSN 0755-4982, http://dx.doi.org/10.1016/j.lpm.2013.11.028.

Anaesthetic management of patient with neurological disease: Focus on regional anaesthesia

Maladie de Friedreich: Les anesthésies locorégionales ne sont pas contre-indiquées et l’efficacité des anesthésies périmédullaires a déjà été rapportée.

Ophthalmic manifestations of inherited neurodegenerative disorders.

Ophthalmic manifestations of inherited neurodegenerative disorders. Kersten HM, Roxburgh RH, Danesh-Meyer HV; Nature Reviews Neurology (2014); doi:10.1038/nrneurol.2014.79; Published online 20 May 2014

Until recently, ocular motor abnormalities were the best-characterized signs of visual system damage in patients with FRDA, although afferent visual pathway abnormalities, including optic neuropathy, have also been described in up to two-thirds of affected individuals.

Epigenetic-based therapies for Friedreich ataxia

Epigenetic-based therapies for Friedreich ataxia. Sandi C, Sandi M, Anjomani-Virmouni S, Al-Mahdawi S and Pook MA. Front. Genet. 5:165. doi: 10.3389/fgene.2014.00165

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A longitudinal VBM study monitoring treatment with erythropoietin in patients with Friedreich ataxia

A longitudinal VBM study monitoring treatment with erythropoietin in patients with Friedreich ataxia. Wolfram Santner, Michael Schocke, Sylvia Boesch, Wolfgang Nachbauer and Karl Egger; Acta Radiologica Short Reports May 2014 3: 2047981614531573, first published on May 12, 2014 doi:10.1177/2047981614531573

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Dysregulation of cellular iron metabolism in Friedreich ataxia: from primary iron-sulfur cluster deficit to mitochondrial iron accumulation

Dysregulation of cellular iron metabolism in Friedreich ataxia: from primary iron-sulfur cluster deficit to mitochondrial iron accumulation. Martelli A and Puccio H (2014). Front. Pharmacol. 5:130. doi: 10.3389/fphar.2014.00130

Keywords: Friedreich Ataxia, frataxin, iron metabolism, iron-sulfur cluster, Mitochondria, Iron Metabolism Disorders

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Project Information:IRON IN THE PATHOGENESIS OF FRIEDREICH'S ATAXIA

Project Information:IRON IN THE PATHOGENESIS OF FRIEDREICH'S ATAXIA. Research Portfolio Online Reporting Tools (NIH), Project Number:5R01NS069454-05; Project Leader: KOEPPEN, ARNULF HANS-WERNER, Awardee Organization: ALBANY RESEARCH INSTITUTE, INC.

Project Information: TUNABLE FRATAXIN REPLACEMENT THERAPY

Project Information: TUNABLE FRATAXIN REPLACEMENT THERAPY . Research Portfolio Online Reporting Tools (NIH), Project Number:1R43NS087730-01; Project Leader: MENDELSOHN, ANDREW R, Awardee Organization: PANORAMA RESEARCH, INC.

PATENT: DIAGNOSIS AND TREATMENT OF FRIEDREICH'S ATAXIA

DIAGNOSIS AND TREATMENT OF FRIEDREICH'S ATAXIA . Bibliographic data: US2014128455 (A1) ― 2014-05-08

Inventor(s): ZAIN-LUQMAN RULA [SE]; BERGQUIST HELEN [SE]; GOOD LIAM [GB] +

Shining a light in the black box of orphan drug pricing

Shining a light in the black box of orphan drug pricing.
Eline Picavet, Thomas Morel, David Cassiman and Steven Simoens; Orphanet Journal of Rare Diseases 2014, 9:62 doi:10.1186/1750-1172-9-62

This study has shown that prices of orphan drugs are influenced by factors such as the availability of an alternative drug treatment, repurposing, etc. Current debate about the affordability of orphan drugs highlights the need for more transparency in orphan drug price setting.

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Mitochondrial dysfunction affecting visual pathways

Mitochondrial dysfunction affecting visual pathways. S. Leruez, P. Amati-Bonneau, C. Verny, P. Reynier, V. Procaccio, D. Bonneau, D. Milea, Revue Neurologique, Available online 3 May 2014, ISSN 0035-3787, http://dx.doi.org/10.1016/j.neurol.2014.03.009.

Keywords: Hereditary optic neuropathy; Leber's hereditary optic neuropathy; Autosomal dominant optic atrophy; Wolfram syndrome; Toxic mitochondrial optic neuropathies; Neuropathie optique héréditaire; Neuropathie optique héréditaire de Leber; Atrophie optique dominante; Syndrome de Wolfram; Neuropathies optiques mitochondriales toxiques; Friedreich's ataxia

Perspectives of drug-based neuroprotection targeting mitochondria

Perspectives of drug-based neuroprotection targeting mitochondria, V. Procaccio, C. Bris, J.M. Chao de la Barca, F. Oca, A. Chevrollier, P. Amati-Bonneau, D. Bonneau, P. Reynier, , Revue Neurologique, Available online 1 May 2014, ISSN 0035-3787, http://dx.doi.org/10.1016/j.neurol.2014.03.005.

Keywords: Mitochondria; Mitochondrial diseases; Neurodegenerative disorders; Pharmacological neuroprotection; Mitochondrie; Maladies mitochondriales; Maladies neurodégénératives; Neuroprotection pharmacologique; ADAlzheimer's disease; AICAR5-aminoimidazole-4-carboxamide ribonucleoside; ALSAmyotrophic lateral sclerosis; AMPAdenosine monophosphate; ATPAdenosine triphosphate; cAMPCyclic AMP; CCCPCarbonylcyanide m-chlorophenylhydrazone; CNSCentral nervous system; ERREstrogen-related receptors; ETCElectron transport chain; FAD/FADHFlavin adenine nucleotide; GDAP1Ganglioside-induced differentiation-associated protein 1; HDHuntington disease; KTPKinetin triphosphate; LHONLeber hereditary optic neuropathy; MAPKMitogen-activated protein kinases; MELASMitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; MERRFMyoclonic epilepsy and ragged red fibers; MFN1/MFN2Mitofusin; MnSODManganese superoxide dismutase; mtDNAMitochondrial genome or DNA; mtPTPMitochondrial permeability transition pore; mTORMammalian target of rapamycin; NAD/NADHNicotinamide adenine dinucleotide; NARPNeurogenic muscle weakness, ataxia, and retinitis pigmentosa; nDNANuclear genome or DNA; NMDAAcide N-methyl-D-aspartic; NOSNitric oxide synthase; NRF1/NRF2Nuclear respiratory factors; OPA1Optic atrophy 1; OXPHOSOxidative phosphorylation; PARLPresenilins-associated rhomboid-like protein; PDParkinson's disease; PGC-1-αPPAR gamma coactivator 1-alpha; PINK1PTEN-induced putative kinase1; PKAProtein kinase A; PPARPeroxisome proliferators-activated receptors; PRCPGC1-related coactivator; CoQCoenzyme Q; RCRespiratory chain; ROSReactive oxygen species; RXRRetinoid X receptors; SIRTSirtuins; TFAMMitochondrial transcription factor A; TFB2/TFB2Transcription factors B1 and B2

Genetics of mitochondrial respiratory chain deficiencies

Genetics of mitochondrial respiratory chain deficiencies, A. Rötig, Revue Neurologique, Available online 3 May 2014, ISSN 0035-3787, http://dx.doi.org/10.1016/j.neurol.2013.11.006.

Keywords: Genetic diseases; Mitochondria; Respiratory chain; Mitochondrie; Chaîne respiratoire; Maladies génétiques

The brain is hypothermic in patients with mitochondrial diseases

The brain is hypothermic in patients with mitochondrial diseases. Mario Rango, Andrea Arighi, Cristiana Bonifati, Roberto Del Bo, Giacomo Comi and Nereo Bresolin; Journal of Cerebral Blood Flow & Metabolism (2014) 34, 915–920; doi:10.1038/jcbfm.2014.38; published online 12 March 2014

Keywords: activation; brain metabolism; brain temperature; mitochondrial diseases; recovery; visual stimulation

R-loops Associated with Triplet Repeat Expansions Promote Gene Silencing in Friedreich Ataxia and Fragile X Syndrome

R-loops Associated with Triplet Repeat Expansions Promote Gene Silencing in Friedreich Ataxia and Fragile X Syndrome . Groh M, Lufino MMP, Wade-Martins R, Gromak N; PLoS Genet 10(5): e1004318. doi:10.1371/journal.pgen.1004318

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Nicotinamide in Friedreich's ataxia: useful or not?

Nicotinamide in Friedreich's ataxia: useful or not?. The Lancet, Available online 30 April 2014, ISSN 0140-6736, http://dx.doi.org/10.1016/S0140-6736(14)60573-0.

Comment

Re-activating the Friedreich’s ataxia gene in patients: early promise for a radical treatment

Re-activating the Friedreich’s ataxia gene in patients: early promise for a radical treatment Ataxia-UK Press release: 1st May 2014

Epigenetic and neurological effects and safety of high-dose nicotinamide in patients with Friedreich's ataxia: an exploratory, open-label, dose-escalation study

Epigenetic and neurological effects and safety of high-dose nicotinamide in patients with Friedreich's ataxia: an exploratory, open-label, dose-escalation study. Vincenzo Libri MD,Cihangir Yandim PhD,Stavros Athanasopoulos MD,Naomi Loyse PhD,Theona Natisvili MSc,Pui Pik Law MSc,Ping Kei Chan PhD,Tariq Mohammad MBBS,Marta Mauri MSc,Kin Tung Tam BSc,James Leiper PhD,Sophie Piper MSc,Aravind Ramesh BM BCh,Michael H Parkinson MBBS,Les Huson PhD,Paola Giunti MD,Prof Richard Festenstein FRCP. The Lancet - 1 May 2014; DOI: 10.1016/S0140-6736(14)60382-2

Dentate nuclei T2 relaxometry is a reliable neuroimaging marker in Friedreich's ataxia

Dentate nuclei T2 relaxometry is a reliable neuroimaging marker in Friedreich's ataxia. C. Bonilha da Silva, F. P. G. Bergo, A. D'Abreu, F. Cendes, I. Lopes-Cendes and M. C. França Jr, European Journal of Neurology. Article first published online: 30 APR 2014 | DOI: 10.1111/ene.12448

Keywords: dentate nuclei; Friedreich's ataxia; MRI ; T2 relaxometry

Pathophysiogical and therapeutic progress in Friedreich ataxia

Pathophysiogical and therapeutic progress in Friedreich ataxia. H. Puccio, M. Anheim, C. Tranchant, Revue Neurologique, Available online 29 April 2014, ISSN 0035-3787, http://dx.doi.org/10.1016/j.neurol.2014.03.008.

Keywords: Friedreich ataxia; Mitochondria; Frataxine; Physiopathology; Therapeutic; Ataxie de Friedreich; Mitochondries; Frataxine; Physiopathologie; Approches thérapeutiques

REGENX Biosciences Enters Into License Agreement With AAVLife for Development of Treatments for Friedreich's Ataxia Using NAV® Vectors

REGENX Biosciences Enters Into License Agreement With AAVLife for Development of Treatments for Friedreich's Ataxia Using NAV® Vectors .

WASHINGTON, DC and PARIS, FRANCE--(Marketwired - Apr 29, 2014) - REGENX Biosciences, LLC announces that the company has entered into an agreement with AAVLife for the development and commercialization of products to treat Friedreich's ataxia (FA) using NAV technology.

"REGENX has been engaged with the team at AAVLife, including its stakeholders like the Friedreich's Ataxia Research Alliance (FARA), since first becoming aware of their gene therapy research results and during the company's process of formation. We are pleased to formally continue our collaboration with a team who has the leadership, expertise, resources, and commitment to patients that is required in order to develop innovative treatments for patients with FA through the application of NAV technology,"

Anaesthesia for correction of scoliosis in pediatric patient with Friedreich‘s ataxia

Anaesthesia for correction of scoliosis in pediatric patient with Friedreich‘s ataxia. G.L. Agámez Medina, E.J. Pantin, J. Lorthé Jr., P.J. Therrien, Revista Española de Anestesiología y Reanimación, Available online 26 April 2014, ISSN 0034-9356, http://dx.doi.org/10.1016/j.redar.2014.03.001.

Anestesia para corrección de escoliosis en paciente pediátrico con ataxia de Friedreich. Caso clínico

Keywords: Ataxia de Friedreich; Anestesia; Anestesia total intravenosa; Miocardiopatía hipertrófica; Diabetes; Escoliosis; Friedreich's ataxia; Anesthesia; Total intravenous anesthesia; Hypertrophic cardiomyopathy; Diabetes; Scoliosis