Changes in mitochondrial glutathione levels and protein thiol oxidation in ∆yfh1 yeast cells and the lymphoblasts of patients with Friedreich's ataxia.

Biochim Biophys Acta. 2011 Nov 11;1822(2):212-225

Bulteau AL, Planamente S, Jornea L, Dur A, Lesuisse E, Camadro JM, Auchère F.
CRICM-INSERM-UMRS975, CNRS UMR 7225-UPMC, Hôpital de la Salpétrière, Physiopathologie cellulaire et moléculaire des maladies mitochondriales, 91, bd de l'hôpital, salle 336, 75651 Paris Cedex 13, France.

Keywords: Friedreich's ataxia (FRDA), frataxin, iron, iron-sulfur cluster, oxidative stress, glutathione homeostasis, protein thiols, GSH/GSSG ratio, aconitase, KGDH.

Small Molecules Mimicking Key Brain Growth Factor Identified By Study

Stanford University Medical Center.

The patents for these four compounds are held by the University of North Carolina and UCSF, where Longo worked before coming to Stanford. While at UNC, Longo founded PharmatrophiX, a company focused on the commercial development of small molecules similar to and including those identified in this study.

Related to: The neurotrophic factor BDNF reduces neurodegeneration induced by frataxin deficiency in neuronal cultures.

DEFINITION OF THE LANDSCAPE OF CHROMATIN STRUCTURE AT THE FRATAXIN GENE IN FRIEDREICH’S ATAXIA

UT GSBS Dissertations and Theses, 12/2011

Keywords: Epigenetics, Chromatin Structure, Histone Modification, Frataxin, FRDA, Neurodegenerative Disease, Repetitive DNA, Triplet repeat, Repeat Diseases

Full text PDF

Orphan designation interferon gamma for the treatment of Friedreich’s ataxia.

On 9 December 2011, orphan designation (EU/3/11/935) was granted by the European Commission to Prof. Roberto Testi, Italy, for interferon gamma for the treatment of Friedreich’s ataxia.

Non-invasive evaluation of buccal respiratory chain enzyme dysfunction in mitochondrial disease: Comparison with studies in muscle biopsy

Molecular Genetics and Metabolism, In Press, Corrected Proof, doi:10.1016/j.ymgme.2011.11.193

Michael J. Goldenthal a, b, Teddy Kuruvilla b, Shirish Damle b, Leon Salganicoff b, Sudip Sheth b, Nidhi Shah b, Harold Marks a, b, Divya Khurana a, Ignacio Valencia a, Agustin Legido a.

a Section of Neurology, Department of Pediatrics, St. Christopher's Hospital for Children, Drexel University College of Medicine, Philadelphia, PA 19134, USA
b Mitochondrial Disease Laboratory, St. Christopher's Hospital for Children, Drexel University College of Medicine, Philadelphia, PA 19134, USA

Keywors: Respiratory chain, Mitochondrial disease, Buccal swab, biopsied skeletal muscle, mitochondrial enzyme activities, Buccal citrate synthase, mitochondrial frataxin levels, relatively high correlation (over 82%), non-invasive.

Differentiating profiles of speech impairments in Friedreich's ataxia: a perceptual and instrumental approach

International Journal of Language & Communication Disorders. doi: 10.1111/j.1460-6984.2011.00078.x

Folker, J. E., Murdoch, B. E., Rosen, K. M., Cahill, L. M., Delatycki, M. B., Corben, L. A. and Vogel, A. P.

Keywords: dysarthria, neurodegenerative diseases, motor speech disorders, Friedreich's ataxia (FRDA), speech sample using an interval rating scale, instrumental measures, respiratory, laryngeal, velopharyngeal, articulatory systems.

Efficacy Study of Epoetin Alfa in Friedreich Ataxia (FRIEMAX)

ClinicalTrials.gov Identifier: NCT01493973

Sponsor: Federico II University

Collaborators: Friedreich's Ataxia Research Alliance (FARA)
Associazione Italiana per la lotta alle Sindromi Atassiche (AISA)

Information provided by (Responsible Party): Alessandro Filla, Federico II University

"This study is not yet open for participant recruitment."

Pharmacodynamic studies of a histone deacetylase inhibitor in Friedreich’s ataxia

EU Clinical Trials Register

EudraCT Number: 2011-002744-27
Sponsor's Protocol Code Number: CR01849
National Competent Authority: UK - MHRA
Clinical Trial Type: EEA CTA
Trial Status: Ongoing
Date on which this record was first entered in the EudraCT database: 2011-09-16

Ataxia UK, Lay summary of Festenstein's hdaci study

HSC20 interacts with Frataxin and is involved in iron-sulfur cluster biogenesis and iron homeostasis

Hum. Mol. Genet. (2011) doi: 10.1093/hmg/ddr582

Yuxi Shan and Gino Cortopassi
Molecular Biosciences, 1120 Haring Hall, University of California, Davis, CA 95616

Keywords: Friedreich’s ataxia (FRDA), frataxin, mitochondrial iron-sulfur cluster (ISC) biosynthesis, ISC assembly machinery, mitochondrial chaperone HSC20, iron-dependent, ISCU/Nfs1, GRP75 ISC chaperone.

Improved Histone Deacetylase Inhibitors as Therapeutics for the Neurodegenerative Disease Friedreich’s Ataxia: A New Synthetic Route

Pharmaceuticals 2011, 4, 1578-1590; doi:10.3390/ph4121578 (doi registration under processing)

Chunping Xu 1, Elisabetta Soragni 1, Vincent Jacques 2, James R. Rusche 2 and Joel M. Gottesfeld 1.
1 Department of Molecular Biology, The Scripps Research Institute, 10550 N. Torreys Pines Road, La Jolla, CA 92037, USA
2 Repligen Corporation, 41 Seyon Street, Waltham, MA 02453, USA

OPEN ACCESS

FULL TEXT PDF

Grant Award: Electrical activity in a stem cell model of Friedreich Ataxia.

The Brain Foundation.
Australian Brain Research - Dr Karina Needham from the University of Melbourne received the Friedreich Ataxia Grant Award for her project title: Electrical activity in a stem cell model of Friedreich Ataxia.

Epigenetic Enhancement of BDNF Signaling Rescues Synaptic Plasticity in Aging

The Journal of Neuroscience, 7 December 2011, 31(49): 17800-17810; doi: 10.1523/​JNEUROSCI.3878-11.2011

Yan Zeng, Miao Tan, Jun Kohyama, Marissa Sneddon, Joseph B. Watson, Yi E. Sun, and
Cui-Wei Xie
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California 90024

Keywords: Aging-related cognitive declines, synaptic plasticity, dendritic spines, reduced histone acetylation, brain-derived neurotrophic factor (Bdnf) gene, H3 and H4 acetylation, HDAC inhibition, 7,8-dihydroxyflavone, trkB, epigenetic or pharmacological.

Substantia nigra hypoechogenicity in friedreich ataxia

Movement Disorders, Article first published online: 9 DEC 2011 | DOI: 10.1002/mds.23989

Heike Stockner MD, Martin Sojer MD, Sascha Hering MD, Wolfgang Nachbauer MD, Klaus Seppi MD, Christoph Schmidauer MD, Werner Poewe MD, Sylvia

Mutations in the dimer interface of dihydrolipoamide dehydrogenase promote site-specific oxidative damages in yeast and human cells

J. Biol. Chem. jbc.M111.274415. First Published on September 19, 2011, doi:10.1074/jbc.M111.274415

Rachael A. Vaubel, Pierre Rustin, and Grazia Isaya


DLD dimer interface mutations may accelerate frataxin turnover via an unknown mechanism

The role of DLD proteolytic activity remains unclear, and will require a better understanding of conditions that accelerate FXN turnover and the identification of additional natural substrates cleaved by DLD.

Structure-function study of cellular iron chemistry

OhioLINK ETD Center, Document number: osu1245414801

Huang, Jia

Keywords: iron-sulfur clusters, frataxin, ferrous iron, scaffold protein human ISU, cytosolic aconitase, IRP1, HscB, ITC.

The yeast metacaspase is implicated in oxidative stress response in frataxin-deficient cells

FEBS Letters - 07 December 2011 (10.1016/j.febslet.2011.12.002)

Sophie Lefevre, Dominika Sliwa, Françoise Auchère, Caroline Brossas, Christoph Ruckenstuhl, Nicole Boggetto, Emmanuel Lesuisse, Frank Madeo, Jean-Michel Camadro, Renata Santos

Keywords: Friedreich ataxia, mitochondrial frataxin, iron-sulfur cluster, heme biosynthesis, antioxidant therapies, hydrogen peroxide, metacaspase.

Posttranslational Modification of Cysteine in Redox Signaling and Oxidative Stress – Focus on S-Glutathionylation

Antioxidants & Redox Signaling. null, Vol. 0, No. ja

Prof. John J. Mieyal, Case Western Reserve University, School of Medicine, Pharmacology, Cleveland, Ohio, United States.
Boon Chock, NHLBI, National Institutes of Health, Laboratory of Biochemistry, Bethesda, Maryland, United States.

Keywords: Reactive oxygen species (ROS), reactive nitrogen species (RNS), cellular signaling pathways, peroxynitrite, cysteine residues, reversible protein-S-glutathionylation, mitochondria, cardiovascular system, neurodegenerative diseases.

DiseaseMeth: a human disease methylation database

Nucl. Acids Res. (2011) doi: 10.1093/nar/gkr1169

Jie Lv, Hongbo Liu, Jianzhong Su, Xueting Wu, Hui Liu, Boyan Li, Xue Xiao, Fang Wang, Qiong Wu, and Yan Zhang

OPEN ACCESS

Keywords: DNA methylation, epigenetic modification, genomic regulation, disease biomarkers, DNA methylation repository, DiseaseMeth, human disease methylation database, gene–disease relationship.

FULL TEXT PDF

Normal left ventricular ejection fraction and mass but subclinical myocardial dysfunction in patients with Friedreich's ataxia.

Eur J Echocardiogr. 2011 Nov 28.

Dedobbeleer C, Rai M, Donal E, Pandolfo M, Unger P.
Department of Cardiology, Erasme Hospital, Université Libre de Bruxelles, 808 Rte de Lennik, Brussels 1070, Belgium.

Keywords: Myocardial involvement, Friedreich's ataxia (FRDA), iron deposits, diffuse fibrosis, focal necrosis.

There is evidence of morphological and functional abnormalities in FRDA patients with normal LVEF and mass.

Specialized Function of Yeast Isa1 and Isa2 Proteins in the Maturation of Mitochondrial [4Fe-4S] Proteins

J. Biol. Chem. 2011 286: 41205-41216. First Published on October 10, 2011, doi:10.1074/jbc.M111.296152

Ulrich Mühlenhoff,
Nadine Richter,
Ophry Pines,
Antonio J. Pierik,
and Roland Lill


Full text PDF

FXN methylation predicts expression and clinical outcome in friedreich ataxia

Annals of Neurology, Accepted manuscript online: 25 NOV 2011 08:37AM EST | DOI: 10.1002/ana.22671

Marguerite V. Evans-Galea, Nissa Carrodus, Simone M. Rowley, Louise A. Corben, Geneieve Tai, Richard Saffery, John C. Galati, Nicholas C. Wong, Jeffrey M. Craig, David R. Lynch, Sean Regner, Alicia F. D. Brocht, Susan L. Perlman, Khalaf O. Bushara, Christopher M. Gomez, George R. Wilmot, Lingli Li, Elizabeth Varley, Martin B. Delatycki and Joseph P. Sarsero

Keywords: Friedreich ataxia (FRDA), expanded GAA repeat, frataxin, epigenetic, clinical parameters, DNA methylation, age of onset, Friedreich Ataxia Rating Scale, disease severity, biomarker.

A TAT-Frataxin fusion protein increases lifespan and cardiac function in a conditional Friedreich’s Ataxia mouse model

Hum. Mol. Genet. (2011) doi: 10.1093/hmg/ddr554

Piyush M. Vyas, Wendy J. Tomamichel, P. Melanie Pride, Clifford M. Babbey, Qiujuan Wang, Jennifer Mercier, Elizabeth M. Martin, and R. Mark Payne

Keywords:Friedreich’s Ataxia (FRDA), frataxin, iron-sulfur (Fe-S) cluster, progressive ataxia, fatal cardiomyopathy, TAT-Frataxin (TAT-FXN) fusion protein, reduced caspase 3 activation, iron oxidant stress, aconitase, heart, protein replacement therapy.

Cardiomyopathy in Friedreich’s Ataxia

Acta Neurologica Belgica, N° 3 (Vol. 111/3) p.183-187, 2011.

Faisal Rahman and Massimo Pandolfo
The John Radcliffe Hospital, Oxford, UK; Service de Neurologie, Hôpital Erasme - Université Libre de Bruxelles, Brussels, Belgium

Keywords: Friedreich’s ataxia (FRDA), spinocerebellar degeneration, cardiomyopathy, frataxin, iron, iron-sulphur clusters, oxidative stress.

Exploring frataxin function.

IUBMB Life. 2011 Nov 17. doi: 10.1002/iub.577. [Epub ahead of print]

Busi MV, Gomez-Casati DF.

Centro de Estudios Fotosintéticos y Bioquímicos (CEFOBI-CONICET), Universidad Nacional de Rosario, Suipacha 531, 2000, Rosario, Argentina and Instituto de Investigaciones Biotecnológicas (IIB-INTECH), Universidad Nacional de General San Martín (UNSAM), Argentina.

Keywords: Frataxin, nuclear-encoded mitochondrial protein, phenotype of Friedreich's ataxia, Fe-S cluster, heme synthesis, energy conversion, oxidative phosphorylation, iron handling, oxidative damage.

Ophthalmic features of Friedreich ataxia

Eye , (18 November 2011) | doi:10.1038/eye.2011.291
Clinical Study

S Noval, I Contreras, I Sanz-Gallego, R K Manrique and J Arpa

"The study show that the visual pathway is affected in FRDA. However, in most patients there is no significant visual impairment"

Keywords: ocular abnormalities,Friedreich ataxia (FRDA), prospective cohort, extensive ophthalmologic examination, low-contrast Sloan letter charts test, retinal nerve fiber layer (RNFL) thickness analysis, optical coherence tomography (OCT).

Primary and Secondary Drug Screening Assays for Friedreich Ataxia.

J Biomol Screen. 2011 Nov 15. [Epub ahead of print]

Cotticelli MG, Rasmussen L, Kushner NL, McKellip S, Sosa MI, Manouvakhova A, Feng S, White EL, Maddry JA, Heemskerk J, Oldt RJ, Surrey LF, Ochs R, Wilson RB.

Keywords: Friedreich ataxia (FRDA), neuro- and cardiodegenerative disorder, frataxin, decreased ISC assembly, mitochondrial iron accumulation, increased oxidative stress, tetrazolium dye WST-1, compounds screen.

Towards a modern definition of vitamin E– evidence for a quinone hypothesis

Bioorganic & Medicinal Chemistry Letters, In Press, Accepted Manuscript, doi:10.1016/j.bmcl.2011.10.117

William D. Shrader a, Akiko Amagata a, Adam Barnes a, Andrew Hinman a, Orion Jankowski a, Edgar Lee a, Viktoria Kheifets a, Ryo Komatsuzaki a, Paul Mollard a, Katsuyuki Murase a, Patrice Rioux c, Kieron Wesson a, Guy Miller a, b

a Edison Pharmaceuticals, Inc., 350 North Bernardo Avenue, Mountain View, CA 94043, USA
b Adjunct Clinical Instructor;Department of Anesthesiology, Critical Care Medicine, Stanford University, Stanford, CA 94305, USA
c Raptor Pharmaceutical Corp. 9 Commercial Blvd., Suite 200 Novato, CA 94949

"has demonstrated a beneficial clinical response in patients with Friedreich’s ataxia"

Keywords: tocoquinone natural product, α-tocopherol quinone (ATQ), α-tocopherol,cellular protectant, oxidative stress, orally bioavailable, pharmacokinetic profile, Friedreich’s ataxia.

New orphan medicinal product designation for Friedreich's Ataxia

10 October 2011, EMA/COMP/811210/2011, Human Medicines Development and Evaluation,
Monthly report, The Committee for Orphan Medicinal Products held its 127th plenary meeting on 5-7 October 2011.

Interferon gamma for treatment of Friedreich’s ataxia, Prof. Roberto Testi.

Hepatic mitochondrial dysfunction in Friedreich Ataxia

BMC Neurology 2011, 11:145 doi:10.1186/1471-2377-11-145

OPEN ACCESS

Sven H Stüwe1, Oliver Goetze2,3, Larissa Arning4, Matthias Banasch2, Wolfgang E Schmidt2, Ludger Schöls5, 6,Carsten Saft1

1 Department of Neurology, Ruhr-University, St. Josef-Hospital, Bochum, Germany
2 Department of Internal Medicine I, Ruhr-University, St. Josef-Hospital, Bochum, Germany
3 Division of Gastroenterology and Hepatology, University Hospital Zurich, Switzerland
4 Department of Human Genetics, Ruhr-University Bochum, Germany
5 Department of Neurology and Hertie Institute for Clinical Brain Research, Tübingen, Germany
6 German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany

Abstract
Background: Mitochondrial dysfunction due to respiratory chain impairment is a key feature in pathogenesis of Friedreich ataxia. Friedreich ataxia affects the nervous system, heart and pancreas.
Methods: We assessed hepatic mitochondrial function by 13C-methionine-breath-test in 16 Friedreich ataxia patients and matched healthy controls.
Results: Patients exhaled significantly smaller amounts of 13CO2 over 90 minutes. Maximal exhaled percentage dose of 13CO2 recovery was reduced compared to controls.
Conclusions: 13C-methionine-breath-test indicates subclinical hepatic mitochondrial
dysfunction in Friedreich ataxia but did not correlate with GAA repeat lengths, disease duration or disease severity.

Changes in mitochondrial glutathione levels and protein thiol oxidation in Δyfh1 yeast cells and the lymphoblasts of patients with Friedreich ataxia

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Available online 11 November 2011, doi:10.1016/j.bbadis.2011.11.003
A.L. Bulteau, S. Planamente, L. Jornea, A. Dur, E. Lesuisse, J.M. Camadro, F. Auchère

Keywords: Friedreich's ataxia; glutathione; iron; mitochondria; thiol oxidation; protein glutathionylation

DNA TRIPLEX STRUCTURES IN HUMAN DISEASE

Rajeswari R. Moganty
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi-110029

KEYWORS: “unusual” DNA structure, human hereditary disorders, the triplet repeat expansion (TRE), Friedreich's ataxia, GAA repeats, Frataxin gene.

Analysis of Echocardiograms in a Large Heterogeneous Cohort of Patients With Friedreich Ataxia

The American Journal of Cardiology, , Available online 10 November 2011, doi:10.1016/j.amjcard.2011.09.025

Sean R. Regner, Sarah J. Lagedrost, Ted Plappert, Erin K. Paulsen, Lisa S. Friedman, Madeline L. Snyder, Susan L. Perlman, Katherine D. Mathews, George R. Wilmot, Kimberly A. Schadt, Martin St. John Sutton, David R. Lynch

Keywords: Friedreich ataxia (FA), cardiomyopathy, echocardiograms, disease duration, subject age, age of onset, functional disability score, GAA repeat length, systolic dysfunction, diastolic dysfunction, hypertrophy.

Annual change in Friedreich's ataxia evaluated by the scale for the assessment and rating of ataxia (SARA) is independent of disease severity

Movement Disorders. doi: 10.1002/mds.23879, Article first published online: 10 NOV 2011

Marelli, C., Figoni, J., Charles, P., Anheim, M., Tchikviladze, M., Vincitorio, C.-M., du Montcel, S. T., Brice, A., Golmard, J. L. and Dürr, A.

"In future therapeutic trials no patient stratification is globally required."

Keywords: Friedreich's ataxia, SARA, clinical rating scale, disease progression

MR spectroscopy and atrophy in Gluten, Friedreich’s and SCA6 ataxias

Acta Neurologica Scandinavica, Article first published online: 10 NOV 2011 | DOI: 10.1111/j.1600-0404.2011.01620.x

M. Hadjivassiliou, L. I. Wallis, N. Hoggard, R. A. Grünewald, P. D. Griffiths and I. D. Wilkinson

Keywords: movement disorders; neuroimaging; SCA6; gluten ataxia; Friedreich’s ataxia; MR spectroscopy

Initial Experience in the Treatment of Inherited Mitochondrial Disease with EPI-743

Molecular Genetics and Metabolism, In Press, Accepted Manuscript, doi:10.1016/j.ymgme.2011.10.009

Gregory M. Enns a, Stephen L. Kinsman b, Susan L. Perlman c, Kenneth M. Spicer d, Jose E. Abdenur e, Bruce H. Cohen f, Akiko Amagata g, Adam Barnes g, Viktoria Kheifets g, William D. Shrader g, Martin Thoolen g, Francis Blankenberg h, Guy Miller g i.

a Department of Pediatrics, Division of Medical Genetics, Lucile Packard Children's Hospital, Stanford University, Stanford, CA 94305–5208, USA
b Division of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA
c Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
d Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC 29425, USA
e Department of Pediatrics, Division of Metabolic Disorders, CHOC Children's Hospital, Orange County, CA 92868, USA
f Department of Neurology, NeuroDevelopmental Science Center, Akron Children's Hospital, Akron, OH 44308, USA
g Edison Pharmaceuticals, 350 North Bernardo Avenue, Mountain View, CA 94043, USA
h Department of Radiology, Division of Pediatric Radiology, Lucile Packard Children's Hospital, Stanford, CA 94305, USA
i Adjunct Clinical Instructor, Department of Anesthesiology, Critical Care Medicine, Stanford University, Stanford, CA 94305, USA

"Data obtained herein suggest that EPI-743 may represent a new drug for the treatment of inherited mitochondrial respiratory chain disorders"

KEYWORDS: Mitochondrial disease; α-tocotrienol quinone; Leigh syndrome; polymerase γ deficiency; MELAS; mitochondrial DNA deletion syndrome, Friedreich ataxia,

Pathophysiology of Friedreich's Ataxia Includes Alterations of Thiol Antioxidants, and Screening Based On This Principle Identifies Small Molecule Drugs With Antioxidant and Frataxin Induction Mechanisms

Free Radical Biology and Medicine, Volume 51, Supplement, 1 November 2011, Pages S85
SFRBM's 18th Annual Meeting: Program and abstracts. doi:10.1016/j.freeradbiomed.2011.10.395

Gino Cortopassi, Robert Schoenfeld, Yuxi Shan, Sunil Sahdeo
University of California, Davis

No abstrac


You can find a similar paper of the same authors in the Strasbourg FARA conference summary.
http://www.curefa.org/_pdf/4thInternationalFAConferenceAbstracts.pdf

Monosodium Luminol could be useful Friedreich’s Ataxia.

Bach Pharma, Inc. and Destum Partners, Inc.

NORTH ANDOVER, Massachusetts – October 31, 2011,

"Approvals are in place to annually treat over a half million cancer patients in the CIS countries alone, a very attractive market opportunity especially for an Eastern European partner. In CNS related diseases, GVT® is the subject of a phase I/II clinical study to treat ataxia-telangiectasia (A-T), a rare childhood genetic disorder, which currently has no effective treatment and leads to early complications of aging and death among its young patients. This study demonstrates strong pre-clinical support for its use in other CNS and/or Orphan diseases such as Parkinson’s, Amyotrophic Lateral Sclerosis (ALS) and Friedreich’s Ataxia."

"The Company intends to focus its clinical efforts through sponsored research!!."

Stem cell. Transplant More Effective When Stem Cells Reprogrammed To A More Basic Form

Wiley-Blackwell. (2011, November 6). "Transplant More Effective When Stem Cells Reprogrammed To A More Basic Form." Medical News Today.

The results confirm that de-differentiation is a workable technique for reengineering cells to an earlier, more primitive state but reprogrammed to have increased cell survival rates and therefore their potential for clinical use.

References: Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential
Yang Liu, Xiaohua Jiang, Xiaohu Zhang, Rui Chen, Tingting Sun, Kin Lam Fok, Jianda Dong, Lai Ling Tsang, Shaoqiong Yi, Yechun Ruan, Jinghui Guo, Mei Kuen Yu, Yuemin Tian, Yiu Wa Chung, Mo Yang, Wenming Xu, Chin Man Chung, Tingyu Li and Hsiao Chang Chan. Accepted manuscript online: 3 NOV 2011 08:50AM EST | DOI: 10.1002/stem.764

A pilot trial of deferiprone for neurodegeneration with brain iron accumulation

haematol November 1, 2011 vol. 96 no. 11 1708-1711, doi: 10.3324/haematol.2011.043018

Giovanni Abbruzzese,Giovanni Cossu, Manuela Balocco, Roberta Marchese, Daniela Murgia, Maurizio Melis, Renzo Galanello, Susanna Barella, Gildo Matta, Uberto Ruffinengo, Ubaldo Bonuccelli and
Gian Luca Forni.

FULL TEXT PDF

Pharmacology: New methods to permeabilize the blood–brain barrier

Nature Reviews Neurology 7, 597 (November 2011) | doi:10.1038/nrneurol.2011.161

Katy Malpass.

Keywords: animal models, tight vascular endothelial junctions, blood–brain barrier (BBB), drug delivery to the brain, neurological disorders.

Systemic Gene Delivery in Large Species for Targeting Spinal Cord, Brain, and Peripheral Tissues for Pediatric Disorders

Molecular Therapy (2011); 19 11, 1971–1980. doi:10.1038/mt.2011.157

Adam K Bevan1,2, Sandra Duque3, Kevin D Foust1, Pablo R Morales4, Lyndsey Braun1, Leah Schmelzer1, Curtis M Chan5, Mary McCrate1,6, Louis G Chicoine1,6, Brian D Coley7, Paul N Porensky3,8, Stephen J Kolb3,9, Jerry R Mendell1,6,9, Arthur HM Burghes2,3 and Brian K Kaspar1,2,3,6,10

1Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
2Integrated Biomedical Sciences Graduate Program, The Ohio State University, Columbus, Ohio, USA
3Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, Ohio, USA
4The Mannheimer Foundation, Inc., Homestead, Florida, USA
5Special Pathology Services, Charles River, Preclinical Services, Reno, Nevada, USA
6Department of Pediatrics, The Ohio State University/Nationwide Children's Hospital, Columbus, Ohio, USA
7Department of Radiology, The Ohio State University, Columbus, Ohio, USA
8Department of Neurological Surgery, The Ohio State University, Columbus, Ohio, USA
9Department of Neurology, The Ohio State University, Columbus, Ohio, USA
10Department of Neurosciences, The Ohio State University, Columbus, Ohio, USA

Our findings support the use of AAV9 for gene transfer to the CNS for disorders in pediatric populations.

MT-OPEN FULL TEXT

Specific Alterations of Carbohydrate Metabolism Are Associated With Hepatocarcinogenesis in Mitochondrially Impaired Mice

Hum. Mol. Genet. (2011) doi: 10.1093/hmg/ddr499

René Thierbach, Simone Florian, Katharina Wolfrum, Anja Voigt, Gunnar Drewes, Urte Blume, Peter Bannasch, Michael Ristow, Pablo Steinberg

Keywords: Friedreich's ataxia, AlbFxn-/- mice, ATP, carbohydrate metabolism, Frataxin, gene disruption, glucose-6-phosphate, glucose transport, glycogen, glycolysis, mitochondria.

Friedreich Ataxia - Pipeline Review, H2 2011

Published by Global Markets Direct on Oct 26, 2011 , 54 pages

This report provides an overview on the therapeutic development for Friedreich Ataxia, it show the Friedreich Ataxia therapeutic pipeline, with latest updates, and late-stage and discontinued projects.

The Role of Mitochondrial Dysfunction in the Pathogenesis of Friedreich's Ataxia

Egypt J. Neurol. Psychiat. Neurosurg. July 2011 Vol. 48 3 : 229 - 234

Hasan G. Nassar,Wael A. Fadel,Wafaa Ibrahim,Wafik S Bahnasy

Keywords: Friedreich's ataxia, Glutathione, Mitochondrial Complexes.

Full text pdf

Evaluation of Myocardial Motion in Friedreich Ataxia Patients and Healthy Volunteers by High Temporal and Spatial Resolution MRI Tissue Phase-mapping Imaging

RSNA Meeting, November 25-30, McCormick Place, Chicago, Illinois
Scientific Informal (Poster) Presentations

Author List: Karsten Kortuem | Christian Oliver Ritter MD | Frank Weidemann | Herbert Koestler PhD | Dietbert Hahn MD | Meinrad Johannes Beer MD

Oligomerization propensity and flexibility of yeast frataxin studied by X-ray crystallography and small-angle X-ray scattering

Journal of Molecular Biology, In Press, Accepted Manuscript, doi:10.1016/j.jmb.2011.10.034

Christopher A.G. Söderberg a, [1], Alexander V. Shkumatov b, 2, Sreekanth Rajan a, Oleksandr Gakh c, Dmitri I. Svergun b, Grazia Isaya c,, Salam Al-Karadaghi a.
a Center for Molecular Protein Science, Institute for Chemistry and Chemical Engineering, Lund University, PO Box 124, SE-221 00 Lund, Sweden
b EMBL, Hamburg Outstation, Notkestraße 85, D-22603 Hamburg, Germany
c Department of Pediatric and Adolescent Medicine and Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA

Keywords: Protein oligomerization; Protein flexibility; metal chaperone; Friedreich's ataxia; Neurodegenerative diseases

The cerebellar cognitive profile

Brain (2011) first published online October 27, 2011 doi:10.1093/brain/awr266

Anna M. Tedesco, Francesca R. Chiricozzi, Silvia Clausi, Michela Lupo, Marco Molinari, and Maria G. Leggio

Keywords: cerebellar role in non-motor functions, cerebellar cognitive affective syndrome, cerebellar damage, ataxia, cerebellum, cognition.

Pioglitazone and bladder cancer

In France, is currently running Friedreich's Ataxia clinical trial with Pioglitazone

The Lancet, Volume 378, Issue 9802, Pages 1543 - 1544, 29 October 2011

Dominique Hillaire-Buys a bEmail Address, Jean-Luc Faillie b c, Jean-Louis Montastruc d e

a CHRU Montpellier, Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital, 34295 Montpellier, France
b Faculty of Medicine, University of Montpellier 1, Montpellier, France
c CHU Nîmes, Department of Epidemiology and Clinical Research, Nîmes University Hospital, Nîmes, France
d CHRU Toulouse, Department of Clinical Pharmacology, Toulouse University Hospital, Toulouse, France
e Department of Pharmacoepidemiology INSERM U1027, Faculty of Medicine, University of Toulouse, Toulouse, France

Keywords: Pioglitazone, peroxisome-proliferator-activated receptor (PPAR)agonist, oral hypoglycaemic drug, bladder cancer, US Food and Drug Administration (FDA), FDA Adverse Event Reporting System, European Medicines Agency.

Pioglitazone and bladder cancer

The Lancet, Volume 378, Issue 9802, Page 1544, 29 October 2011, doi:10.1016/S0140-6736(11)61663-2

Robert Elford Ryder
Department of Diabetes and Endocrinology, City Hospital, Birmingham B18 7QH, UK

Keywords: French and German regulatory bodies, risk of bladder cancer, European Medicines Agency (EMA), increased fractures, heart failure, type 2 diabetes, cardiovascular benefit.

"Despite the EMA's conclusion over bladder cancer risk, the overall risk—benefit balance remains strongly in favour of continued use of pioglitazone, especially in patients with ischaemic heart disease (but without heart failure) or stroke"

Pioglitazone and bladder cancer — Authors' reply

Erland Erdmann a, John A Dormandy b, Massimo Massi-Benedetti c, Robert Spanheimer

­Genes en lugar de fármacos

Interesting TV report on gene therapy (Spanish language)

Hidden Administration of Drugs

Clinical Pharmacology & Therapeutics 90, 651-661 (November 2011) | doi:10.1038/clpt.2011.206

F Benedetti, E Carlino and A Pollo

Keywords: placebo-controlled trials, dummy treatment (placebo), psychological component, psychology and pharmacodynamics.

An unusual atrial tachycardia in a patient with Friedreich ataxia

Europace (2011) 13 (11): 1660-1661. doi: 10.1093/europace/eur156

Justin M.S. Lee1,*, Ian Turner1, Ajit Agarwal2 and Simon P. Fynn1
1Department of Cardiology, Papworth Hospital, Cambridge CB23 3RE, UK
2Department of Cardiology, West Suffolk Hospital, Bury St Edmunds, IP33 2QZ, UK

Keywords: atrial tachycardia, Friedreich ataxia, arrhythmi, linear ablation.

Anaesthesia for a patient with Friedreich's ataxia.

Indian J Anaesth. 2011 Jul;55(4):418-20.

Ganesan I.

Department of Anaesthesiology, SRM Medical College Hospital and Research Centre, Chennai, Tamil Nadu, India.

NO ABSTRAC

Inactivation of mitochondrial aspartate aminotransferase contributes to the respiratory deficit of yeast frataxin-deficient cells

Biochem. J. (2011) Immediate Publication, doi:10.1042/BJ20111574
Dominika Sliwa, Julien Dairou, Jean-Michel Camadro and Renata Santos
Institut Jacques Monod, Paris, France

Keywords: Friedreich ataxia, frataxin, iron homeostasis, hypersensitivity to oxidants, NAD+ and NADH, malate-aspartate NADH shuttle, mitochondrial aspartate aminotransferase (Aat1), mitochondrial acetylated proteins, post-translational modification.

FULL TEXT PDF

Physiological oxygen level is critical for modeling neuronal metabolism in vitro

Zhu, J., Aja, S., Kim, E.-K., Park, M. J., Ramamurthy, S., Jia, J., Hu, X., Geng, P. and Ronnett, G. V. (2011), Journal of Neuroscience Research. doi: 10.1002/jnr.22765

KEYWORDS: In vitro models, nonphysiological conditions, ambient (21%) oxygen levels, physiological oxygen level (5% O2), glucose uptake, glycolysis, glucose oxidation , fatty acid oxidation, AMPK activity, intracellular ATP level,

"Oxygen level is an important parameter to consider when modeling neuronal responses to stress in vitro".

Un score pour évaluer la stabilité au cours de la marche : méthodologie et validation chez le patient atteint d’ataxie de Friedreich

A. Gouelle a, ⁎, F. Mégrot b, A. Yelnik c, G.-F. Penneçot d
a Plate-forme d’analyse du mouvement, hôpital Robert-Debré, AP–HP, 48, boulevard Sérurier, 75019 Paris, France
b Unité clinique d’analyse de la marche et du mouvement, CMPRE Bois-Larris, Lamorlaye, France
c Service de médecine physique et de réadaptation, hôpital Fernand-Widal, Paris, France
d Service de chirurgie orthopédique, hôpital Robert-Debré, Paris, France


KEYWORDS : Score, Marche, Stabilité dynamique, Paramètres spatiotemporels

FULL TEXT PDF

Friedreich ataxia: The vicious circle hypothesis revisited

BMC Medicine 2011, 9:112doi:10.1186/1741-7015-9-112, Published: 11 October 2011

Aurelien Bayot, Renata Santos, Jean-Michel Camadro and Pierre Rustin

OPEN ACCES

Abstract (provisional)
Friedreich ataxia, the most frequent progressive autosomal recessive disorder involving the central and peripheral nervous system, is mostly associated with an unstable expansion of GAA trinucleotide repeats in the first intron of the FXN gene which encodes the mitochondrial frataxin protein. Since FXN was shown to be involved in Friedreich ataxia in the late 1990s, the consequence of frataxin loss of function has been generating vigorous debate. Very early on, we suggested a unifying hypothesis according to which frataxin deficiency leads to a vicious circle of faulty iron handling, impaired iron-sulfur cluster synthesis, and increased oxygen radical production. However, data from cell and animal models now indicate that iron accumulation is an inconsistent and late event and that frataxin deficiency does not always impair the activity of iron-sulfur cluster-containing proteins. In contrast, frataxin deficiency appears consistently associated with increased sensitivity to reactive oxygen species, as opposed to increased oxygen radical production. Compiling findings from fundamental researches to clinical observations, we defend here the opinion that the very first consequence of frataxin depletion is indeed an abnormal oxidative status which initiates the pathogenic mechanism underlying Friedreich ataxia.

FULL TEXT PDF

Mesenchymal Stem Cells Restore Frataxin Expression and Increase Hydrogen Peroxide Scavenging Enzymes in Friedreich Ataxia Fibroblasts

PLoS ONE 6(10): e26098. doi:10.1371/journal.pone.0026098 (2011)

Kemp K, Mallam E, Hares K, Witherick J, Scolding N, et al.
Multiple Sclerosis and Stem Cell Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom

OPEN ACCESS

Abstract Top

Dramatic advances in recent decades in understanding the genetics of Friedreich ataxia (FRDA)—a GAA triplet expansion causing greatly reduced expression of the mitochondrial protein frataxin—have thus far yielded no therapeutic dividend, since there remain no effective treatments that prevent or even slow the inevitable progressive disability in affected individuals. Clinical interventions that restore frataxin expression are attractive therapeutic approaches, as, in theory, it may be possible to re-establish normal function in frataxin deficient cells if frataxin levels are increased above a specific threshold. With this in mind several drugs and cytokines have been tested for their ability to increase frataxin levels. Cell transplantation strategies may provide an alternative approach to this therapeutic aim, and may also offer more widespread cellular protective roles in FRDA. Here we show a direct link between frataxin expression in fibroblasts derived from FRDA patients with both decreased expression of hydrogen peroxide scavenging enzymes and increased sensitivity to hydrogen peroxide-mediated toxicity. We demonstrate that normal human mesenchymal stem cells (MSCs) induce both an increase in frataxin gene and protein expression in FRDA fibroblasts via secretion of soluble factors. Finally, we show that exposure to factors produced by human MSCs increases resistance to hydrogen peroxide-mediated toxicity in FRDA fibroblasts through, at least in part, restoring the expression of the hydrogen peroxide scavenging enzymes catalase and glutathione peroxidase 1. These findings suggest, for the first time, that stem cells may increase frataxin levels in FRDA and transplantation of MSCs may offer an effective treatment for these patients.

Full text PDF

Rare Diseases and Orphan Products: Accelerating Research and Development (2011)

THE NATIONAL ACADEMIES PRESS

Modeling neurological disorders by human induced pluripotent stem cells

Journal of Biomedicine and Biotechnology, Received 11 July 2011; Accepted 6 October 2011 Academic Editor: Ken-ichi Isobe

Tanut Kunkanjanawan, Rangsun Parnpai, and Parinya Noisa
Received 11 July 2011; Accepted 6 October 2011Academic Editor: Ken-ichi Isobe

Friedreich's Ataxia in pg 11.

Fulltext PDF

Cell modelsof a neural lineage to study the effects of frataxin deficiency

Herbert-Worch-Foundation

A Spanish University developed cell models to study the effects of frataxin deficiency on human neuron-like cells.

Companies from all countries interested in putting on the market a new neuronal cell model for Friedreich´s ataxia are sought.

Current and Potential Domain of Application: Screening and testing of possible therapeutic compounds. Current Stage of Development: development phase - Laboratory tested.

Les effets secondaires du principe de précaution

Article in: Association française contre les myopathies (AFM) Blog (3/10/11)

Health authorities (FDA, EMEA, national agencies, etc.) have the obligation to ensure our health and safety from new drugs or treatments, but sometimes look like they know very little about our disease, in this case, in France are blocking a compassionate use due a the very remote possibility of an side effect that can appears in old age, unfortunately, few patients will reach if there is no effective treatment, and can not test it.

It is very sad, french patients which participated in the Dr. Isabelle Husson and Pierre Rustin Pioglitazone clinical trial, when they finish the two years clinical trial, they can continue with the Pioglitazone as compassionate use, now, the authorities ban this option, although as some patiens explain, they feel that get improvements. The reason, a very little possibility to develop a side effec, prostate cancer, a possibility that unfortunately is not logical for FA patiens, due to the typical disease life expectancy.

What is the OX1?

The OX1 or OXIGON (TM) is the Indole-3-propionic acid (IPA) (SYNONYMS: 3-Indolepropionic Acid, 1H-Indole-3-propanoic acid, beta-Indole-3-propionic acid, 3-(3-Indolyl)propanoic acid, 3-(3-Indolyl)propionic acid, 3-Indolyl propionic acid). It is a compound closely related to melatonin, but with a much more powerful antioxidant action.

Has been previously proposed as a possible Alzheimer’s disease therapy, after, it is being investigated for other neurodegenerative diseases such HD, Friedreich's Ataxia, ataxia, ..., for its neuroprotective action. As usual, the major efforts are focused in AD, and most scientific "public" information is related to AD.

Curiously, it also has application in gardening, is an auxin (plant hormone), and it is used as a growth roots stimulator . :-)

References:

Potent neuroprotective properties against the Alzheimer beta-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid. Chyan YJ, Poeggeler B, Omar RA, Chain DG, Frangione B, Ghiso J, Pappolla MA. J Biol Chem. 1999

Development of indole-3-propionic acid (OXIGON) for Alzheimer's disease. Bendheim PE, Poeggeler B, Neria E, Ziv V, Pappolla MA, Chain DG. J Mol Neurosci. 2002

Indole-3-propionic acid attenuates neuronal damage and oxidative stress in the ischemic hippocampus. Hwang IK, Yoo KY, Li H, Park OK, Lee CH, Choi JH, Jeong YG, Lee YL, Kim YM, Kwon YG, Won MH. J Neurosci Res. 2009

A novel endogenous indole protects rodent mitochondria and extends rotifer lifespan. Poeggeler B, Sambamurti K, Siedlak SL, Perry G, Smith MA, Pappolla MA. PLoS One. 2010

Melatonin treatment restores mitochondrial function in Alzheimer's mice: a mitochondrial protective role of melatonin membrane receptor signaling. Dragicevic N, Copes N, O'Neal-Moffitt G, Jin J, Buzzeo R, Mamcarz M, Tan J, Cao C, Olcese JM, Arendash GW, Bradshaw PC. J Pineal Res. 2011.

Intellect obtains pharmacokinetic data from OX1 Phase 1b trial for Alzheimer's disease

Intellect Neurosciences Files Orphan Drug Application in the United States for Its Clinical Candidate OX1 for the Treatment of Friedreich's Ataxia

Clinical proof of concept patient trials for OX1 in Friedreich's Ataxia

ViroPharma Licenses Rights From Intellect Neurosciences for Product Candidate for Friedreich's Ataxia

ViroPharma Licenses Rights From Intellect Neurosciences for Product Candidate for Friedreich's Ataxia

EXTON, Pa., Sept. 30, 2011 /PRNewswire via COMTEX/ -- ViroPharma Incorporated (VPHM) today announced the license of worldwide rights from Intellect Neurosciences, Inc. (ILNS) to its clinical stage drug candidate, OX1, being developed for the treatment of Friedreich's Ataxia (FA), a rare, hereditary, progressive neurodegenerative disease. read more ...

Gene therapies advance towards finish line

Nature Reviews Drug Discovery 10, 719-720 (October 2011) | doi:10.1038/nrd3572

Asher Mullard

News and Analysis. Over a decade since gene therapy development came to a near standstill with the death of a clinical trial participant, the field is overcoming issues of immunogenicity, carcinogenicity, manufacturing and small patient populations.....

“I am certain that a gene therapy is going to cross the finish line within the next year or two, in either the United States or the European Union,” says Coté.

Neural Substrates for the Motivational Regulation of Motor Recovery after Spinal-Cord Injury

I am aware that the casuistry of a spinal injury is very distant from the AF, but this paper shows a link between the willingness and recovery progress , or in our case, to preserve the faculties for longer.

PLoS ONE, 2011; 6 (9): e24854 DOI: 10.1371/journal.pone.0024854

Yukio Nishimura1,2,3,7*, Hirotaka Onoe3,4, Kayo Onoe5, Yosuke Morichika1, Hideo Tsukada3,6, Tadashi Isa1,3,7

1 Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki, Japan, 2 Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Tokyo, Japan, 3 Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Japan, 4 Functional Probe Research Laboratory, RIKEN Center for Molecular Imaging Science, Kobe, Japan, 5 Molecular Dynamics Laboratory, RIKEN Center for Molecular Imaging Science, Kobe, Japan, 6 Central Research Laboratory, Hamamatsu Photonics, Hamamatsu, Japan, 7 Graduate University for Advanced Studies (SOKENDAI), Hayama, Japan

OPEN ACCESS

"It is believed that depression impedes and motivation enhances functional recovery after neuronal damage such as spinal-cord injury and stroke. However, the neuronal substrate underlying such psychological effects on functional recovery remains unclear. "

FULL TEXT PDF



In layman's words

ScienceDaily (Sep. 28, 2011) — An effective recovery has been observed in stroke patients and those with spinal cord injuries who have strong vitality and motivation to rehabilitate in clinical practice. However, it was not really clear how motivation facilitates functional recovery in brain science. read more....

Understanding the function of frataxin in eukaryotes

PhD Research Project, Medical Research Council, National Institute for Medical Research, PhD Supervisor: Dr A Pastore
Application Deadline: 30 November 2011

The work should lead both to a better understanding of the mechanisms of iron-sulfur cluster formation and to the establishment of the frataxin function.

Mitochondrial disorders and the eye

Eye and Brain, September 2011 Volume 2011:3 Pages 29 - 47
DOI: http://dx.doi.org/10.2147/EB.S16192

Van Bergen NJ, Chakrabarti R, O’Neill EC, Crowston JG, Trounce IA

Keywords: mitochondria, disease, retina, eye, aging, neuroprotection, Friedreich’s ataxia.

OPEN ACCESS

FULL TEXT PDF

1st iissue off EFACTS NEWS

The EFACTS (European Friedreich’s Ataxia Consortium for Translational Studies) Consortium will publish the newsletter EFACTS NEWS aimed at communicating the activities of the Network and progress in FRDA research to affected families, the general public, health care professionals and the scientific community. The newsletter will be published annually and the issues will appear on the EFACTS Website

Subscribe Newsletter

Mutation in Fe-S scaffold Isu bypasses frataxin deletion

Biochem. J. (2011) Immediate Publication, doi:10.1042/BJ20111637

Heeyong Yoon, Ramesh Golla, Emmanuel Lesuisse, Jayashree Pain, Jason Donald, Elise R. Lyver, Debkumar Pain and Andrew Dancis
University of Pennsylvania, Philadelphia, U.S.A.

Keywords: Frataxin, Friedreich’s ataxia, iron homeostasis, Fe-S cluster assembly, cysteine desulfurase (Nfs1), accessory protein (Isd11), scaffold protein (Isu), single amino acid substitution.

FULL TEXT PDF

Orphan Drugs, Big Pharma

Human Gene Therapy. September 2011, 22(9): 1035-1038. doi:10.1089/hum.2011.2515.

—Alex Philippidis, Senior News Editor

Safety and Efficacy of Intravenous Immune Globulin in Treating Friedreich's Ataxia and Spinocerebellar Ataxia

Sponsor: University of South Florida
Collaborator: Baxter Healthcare Corporation
Information provided by (Responsible Party): Theresa Zesiewicz, University of South Florida
ClinicalTrials.gov Identifier: NCT01350440

This study is currently recruiting participants. (Last Updated on September 9, 2011)

Neuroprotective and metabolic effects of resveratrol: Therapeutic implications for huntington's disease and other neurodegenerative disorders

doi:10.1016/j.expneurol.2011.08.014

Giulio Maria Pasinettilow asterisk, a, E-mail The Corresponding Author, Jun Wanga, Philippe Marambauda, Mario Ferruzzia, Paul Gregora, Lindsay Alexis Knablea and Lap Hoa
a Center of Excellence for Research in Complementary and Alternative Medicine in Alzheimer's Disease, Department of Neurology, Mount Sinai School of Medicine, New York, NY 1002

Keywords: Resveratrol, polyphenolic compound, aging, metabolic disorders, inflammation , cancer, currently being tested in numerous clinical trials, key metabolic sensor/effector proteins, potential neuroprotective effects, SRT501 , Huntington's disease (HD)., diabetes mellitus.

Iron Efflux from Oligodendrocytes Is Differentially Regulated in Gray and White Matter

The Journal of Neuroscience, 14 September 2011, 31(37): 13301-13311; doi: 10.1523/​JNEUROSCI.2838-11.2011

Katrin Schulz 1, Chris D. Vulpe 2, Leah Z. Harris 3, and Samuel David 1
1Center for Research in Neuroscience, The Research Institute of the McGill University Health Center, Montreal, Quebec H3G 1A4, Canada,
2Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California 94720, and
3Department of Pediatrics, Vanderbilt University, Nashville, Tennessee 37232

Keywords: Accumulation of iron, neurodegenerative diseases, generate toxic free radicals, Iron homeostasis, ferroportin, ferroxidase, astrocytes, oligodendrocytes, hephaestin.

"Dysregulation of such efflux mechanisms leads to iron accumulation in the CNS."

Evaluation of histone deacetylase inhibitors as therapeutics for neurodegenerative diseases.

Methods Mol Biol. 2011;793:495-508.

Soragni E, Xu C, Cooper A, Plasterer HL, Rusche JR, Gottesfeld JM.
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA, USA.

Keywords: neurodegenerative diseases, aberrant gene expression, pimelic o-aminobenzamide histone deacetylase (HDAC) inhibitors, Friedreich's ataxia (FRDA), Huntington's disease (HD), cellular models.

Superando la barrera hematoencefálica

Traduccion de EurekAlert!.org, 13 septiembre 2011, que se encuentra en Bitnavegantes


"Por primera vez, los investigadores descubrieron que, cuando los receptores de adenosina se activan en las células que forman la barrera hematoencefálica, se abre una puerta de entrada a través dicha barrera."

Breaching the blood-brain barrier

EurekAlert!, Public release date: 13-Sep-2011

"For the first time, the researchers discovered that when adenosine receptors are activated on cells that comprise the blood-brain barrier, a gateway into the blood-brain barrier can be established."

Adenosine Receptor Signaling Modulates Permeability of the Blood–Brain Barrier

The Journal of Neuroscience, 14 September 2011, 31(37): 13272-13280; doi: 10.1523/​JNEUROSCI.3337-11.2011

Aaron J. Carman, Jeffrey H. Mills, Antje Krenz, Do-Geun Kim, and Margaret S. Bynoe
Department of Microbiology and Immunology, Cornell University, College of Veterinary Medicine, Ithaca, New York 14853

Acute myocardial infarction after botulinum toxin injection.

QJM (2011) 104(7): 615-616

B.E. Stähli, L. Altwegg, T.F. Lüscher and R. Corti
Department of Cardiology, Cardiovascular Center, University Hospital Zürich, Zürich, Switzerland

Keywords: Friedreich ataxia, ventricular fibrillation, botulinum toxin A, neurogenic bladder dysfunction,thrombotic occlusion.

Shuttle-Mediated Drug Delivery to the Brain.

Angew Chem Int Ed Engl. 2011 Jun 30. doi: 10.1002/anie.201006565. [Epub ahead of print]

Malakoutikhah M, Teixidó M, Giralt E.

Institute for Research in Biomedicine (IRB Barcelona), Barcelona (Spain)

Keywords: shuttle-mediated drug delivery, blood-brain barrier (BBB), central nervous system, vector-mediated approach, ability to cross the BBB.

Mesenchymal stem cells: from experiment to clinic

Fibrogenesis & Tissue Repair 2011, 4:20 doi:10.1186/1755-1536-4-20
William R Otto1 and Nicholas A Wright2

1 Histopathology Laboratory, Cancer Research UK, London Research Institute, London, UK. 2 Blizard Institute, Barts and The London, Queen Mary’s School of Medicine and Dentistry, London, UK.

"Good review, defines the current state of research and use of Mesenchymal stem cells"

Importance of Iron Chelation in Free Radical-Induced Oxidative Stress and Human Disease.

Curr Pharm Des. 2011 Sep 9,

Jomova K, Valko M.
Faculty of Chemical and Food Technology, Slovak Technical University, Bratislava, Slovakia.

Keywords: Iron, redox active metal, hemochromatosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, Friedreich's ataxia, neurological disorders, cancer, Fanconi anemia, stroke, ageing, Fenton reaction, reactive oxygen species (ROS), iron-designed chelators.

A listing of clinical trials currently looking for volunteers to enroll in Friedreich's Ataxia studies.

Austria, Innsbruck :

Patient Reported Outcomes in Friedreich's Ataxia Patients After Withdrawal From Treatment With Idebenone (PROTI)

Roles of Porphyrin and Iron Metabolisms in the δ-Aminolevulinic Acid (ALA)-induced Accumulation of Protoporphyrin and Photodamage of Tumor Cells

Photochemistry and Photobiology, Volume 87, Issue 5, pages 1138–1145, September/October 2011, DOI: 10.1111/j.1751-1097.2011.00950.x

Yoshiko Ohgari, Yoshinobu Miyata, Taeko Miyagi, Saki Gotoh, Takano Ohta, Takao Kataoka, Kazumichi Furuyama and Shigeru Taketani

"The decrease of mitochondrial utilization of iron by the knockdown of mitoferrin-2 and frataxin also enhanced the ALA effect."

PEP-1-Frataxin Significantly Increases Cell Proliferation and Neuroblast Differentiation by Reducing Lipid Peroxidation in the Mouse Dentate Gyrus.

Neurochem Res. 2011 Sep 1,

Kim W, Kim DW, Shin BN, Yoo DY, Nam SM, Kim MJ, Choi JH, Yoon YS, Won MH, Choi SY, Hwang IK.

Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, South Korea.

Keywords: Frataxin, cell proliferation, neuroblast differentiation, PEP-1-frataxin fusion protein, decreasing lipid peroxidation, blood-brain barrier, dentate gyrus.

Articulatory Kinematics in the Dysarthria Associated with Friedreich's Ataxia.

Motor Control. 2011 Jul;15(3):376-89.

Folker JE, Murdoch BE, Cahill LM, Rosen KM, Delatycki MB, Corben LA, Vogel AP.

School of Health and Rehabilitation Sciences, The University of Queensland, St Lucia, Qld, Australia.

KEYWORDS: Electromagnetic articulography (EMA), dysarthria, Friedreich's ataxia (FRDA).

Drug first to demonstrate neurological improvement in patients with Friedreich’s ataxia

Website: USF HEALTH (UNIVERSITY OF SOUTH FLORIDA)

Preliminary trial findings shared with FARA-USF research symposium participants

"For the first time, an investigative drug has significantly improved the neurological function of patients with Friedreich’s ataxia."

“This is the first clinical trial where patients were given a drug and they’ve shown neurological improvement,” Farmer said. “It’s incredibly hopeful… but there’s still a lot of work ahead. We need to show the drug really makes a difference over six months or a year.”

read more....

Human umbilical cord blood-derived mononuclear cell transplantation: case series of 30 subjects with Hereditary Ataxia

Journal of Translational Medicine 2011, 9:65 doi:10.1186/1479-5876-9-65

OPEN ACCESS

Wan-Zhang Yang1, Yun Zhang2, Fang Wu1, Min Zhang1, SC Cho3, Chun-Zhen Li1, Shao-Hui Li1, Guo-Jian Shu1, You-Xiang Sheng1, Ning Zhao1, Ying Tang1, Shu Jiang2, Shan Jiang2, Matthew Gandjian4, Thomas E Ichim4* and Xiang Hu2

1 Department of Rehabilitation Medicine, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen, China

2 Shenzhen Beike Cell Engineering Research Institution, Shenzhen, China

3 Department of Neurology and Neurosurgery, Stanford University, Stanford, CA, USA

4 Medistem Inc, San Diego, CA, USA

FULL TEXT PDF

The PPAR-gamma agonist pioglitazone modulates inflammation and induces neuroprotection in parkinsonian monkeys

Journal of Neuroinflammation 2011, 8:91 doi:10.1186/1742-2094-8-91

OPEN ACCESS

Christine R Swanson, Valerie Joers, Viktorya Bondarenko, Kevin Brunner, Heather A Simmons, Toni E Ziegler, Joseph W Kemnitz, Jeffrey A Johnson and Marina E Emborg

Activation of the peroxisome proliferator-activated receptor gamma (PPAR-gamma) has been proposed as a possible neuroprotective strategy to slow down the progression of early Parkinson's disease (PD). Here we report preclinical data on the use of the PPAR-gamma agonist pioglitazone (Actos(R); Takeda Pharmaceuticals Ltd.) in a paradigm resembling early PD in nonhuman primates.

Clinically, pioglitazone has been tested for Alzheimer disease, multiple sclerosis, autism, stroke, amyotrophic lateral sclerosis, and Friedreich’s Ataxia. The results of these small clinical trials suggest that its administration can benefit patients with neurological disorders.

FULL TEXT PDF

Movement disorders in spinocerebellar ataxias

Movement Disorders. doi: 10.1002/mds.23928 (Article first published online: 24 AUG 2011)

Pedroso, J. L., Felicio, A. C., Braga-Neto, P. and Barsottini, O. G.

"No abstract is available for this article."

MDA has awarded a research grant to Des Richardson, professor and senior principal research fellow at the University of Sydney (Australia) to continued research into iron metabolism in Friedreich's ataxia (FA).

The aim of Richardson's studies is to examine the role of altered iron metabolism in the cellular energy factories called mitochondria.

Dual role of the mitochondrial protein frataxin in astrocytic tumors

Laboratory Investigation , (22 August 2011) | doi:10.1038/labinvest.2011.130

Elmar Kirches, Nadine Andrae, Aline Hoefer, Barbara Kehler, Kim Zarse, Martin Leverkus, Gerburg Keilhoff, Peter Schonfeld, Thomas Schneider, Annette Wilisch-Neumann and Christian Mawrin

Keywords: frataxin (FXN), mitochondrial iron homeostasis, iron–sulfur cluster biogenesis, electron transport chain, reactive oxygen species (ROS), Friedreich's ataxia, suggest a dual, pro-proliferative but chemosensitizing role in astrocytic tumors.

MDA FUNDS UNIVERSITY OF PENNSYLVANIA NEUROLOGIST EXPLORING LINK BETWEEN DIABETES AND FRIEDREICH’S ATAXIA

TUCSON, Ariz., Aug. 23, 2011–The Muscular Dystrophy Association has awarded neurology professor David Lynch, M.D., Ph.D., at University of Pennsylvania School of Medicine, a $202,222 grant to study the connection between diabetes and Friedreich’s Ataxia (FA). Lynch has been an MDA-funded investigator for many years.

Autosomal recessive cerebellar ataxias: the current state of affairs

J Med Genet doi:10.1136/jmedgenet-2011-100210

S Vermeer1, B P C van de Warrenburg2, M A A P Willemsen2, M Cluitmans1, H Scheffer1,3, B P Kremer4, N V A M Knoers1,5
1Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 2Department of Neurology, Donders Institute of Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 3Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 4Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands, 5Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands

Keywords: hereditary ataxias, autosomal recessive cerebellar ataxias (ARCAs), cerebellar syndrome, atypical phenotypes, genetic heterogeneity, ARCA genes, pathophysiological mechanisms.

LUNDBECK, Lu AA24493 the Clinical Phase II results do not support further development of the drug in FA

A novel deletion-insertion mutation identified in exon 3 of FXN in two siblings with a severe Friedreich ataxia phenotype.

Neurogenetics. 2011 Aug 10.

Evans-Galea MV, Corben LA, Hasell J, Galea CA, Fahey MC, du Sart D, Delatycki MB.

Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Australia.

Keywords: Friedreich ataxia (FRDA), GAA trinucleotide repeat expansion in the first intron of FXN, frataxin, early onset of symptoms, novel deletion-insertion mutation in exon 3 (c.371_376del6ins15).

Friedreich ataxia.

Handb Clin Neurol. 2011;103:275-94.

Pandolfo M.

Other autosomal recessive and childhood ataxias.

Handb Clin Neurol. 2011;103:343-57.

De Michele G, Filla A.

Keywords: "early-onset cerebellar ataxia with retained tendon reflexes" (EOCA), Friedreich ataxia (FRDA), preserved knee jerks, absence of cardiomyopathy, optic atrophy, diabetes mellitus, several FRDA patients present with an EOCA-like phenotype, Cerebellar ataxia with hypogonadism, autosomal recessive ataxia of Charlevoix-Saguenay (ARSACS), infantile-onset spinocerebellar ataxia (IOSCA).

Targeting Mitochondrial Dysfunction and Neurodegeneration by Means of Coenzyme Q10 and its Analogues.

Curr Med Chem. 2011 Aug 9.

Orsucci D, Mancuso M, Ienco EC, Logerfo A, Siciliano G.
Department of Neuroscience, Neurological Clinic, University of Pisa, Italy

Keywords: Coenzyme Q10, respiratory chain, antioxidant properties, mitochondrial disorders, reactive oxygen species, idebenone, mitoquinone, Friedreich ataxia, cardiac hypertrophy, improve neurological function.

Friedreich's Ataxia: a review from a cardiology perspective.

Ir J Med Sci. 2011 Aug 7.

Bourke T, Keane D.
Cardiac Arrhythmia Service, St Vincent's University Hospital, Dublin, Ireland

Keywords: Friedreich's Ataxia (FA), morbidity, mortality, premature death, Hypertrophic cardiomyopathy, cardiac examination, ECG, ECHO, left ventricular outflow gradient.

Glutathione: a key component of the cytoplasmic labile iron pool.

Biometals. 2011 Jul 17.

Hider RC, Kong XL.
Institute of Pharmaceutical Science, King's College London

Keywords: cytoplasmic labile iron pool, heme, iron sulfur cluster synthesis, iron(II)glutathione, iron(II), manganese(II),synthesis of Fe-S cluster proteins.

STATegics, Inc. Announces a Grant From Friedreich's Ataxia Research Alliance to Support Its Program to Develop Small Molecule Mimetics of Erythropoietin for the Treatment of Friedreich's Ataxia

MENLO PARK, Calif., Aug. 2, 2011 (GLOBE NEWSWIRE) -- STATegics, Inc. announced today that the Friedreich's Ataxia Research Alliance (FARA) has awarded the Company $152,690 to advance its proprietary small molecule erythropoietin mimetic compounds for the treatment of Friedreich's ataxia (FRDA),read more

The scale for the assessment and rating of ataxia correlates with dysarthria assessment in Friedreich's ataxia

Journal of Neurology, DOI: 10.1007/s00415-011-6192-9

Andreas Eigentler, Johanna Rhomberg, Wolfgang Nachbauer, Irmgard Ritzer, Werner Poewe and Sylvia Boesch

Keywords: Dysarthria, motor functions, Frenchay Dysarthria Assessment, clinical and logopedic methodology, reflexes, palate, tongue, intelligibility.

The role of induced pluripotent stem cells in regenerative medicine: neurodegenerative diseases

Stem Cell Research & Therapy 2011, 2:32 doi:10.1186/scrt73, Published: 28 July 2011

Jun Peng and Xianmin Zeng

Keywords: Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Friedreich's ataxia, neurodegenerative diseases, no effective clinical therapies, human adult somatic cells, induced pluripotent stem cells (iPSCs), in vitro disease mechanism study, in vivo cell replacement therapy.

A pilot trial of deferiprone for neurodegeneration with brain iron accumulation.

Haematologica. 2011 Jul 26. [Epub ahead of print]

Abbruzzese G, Cossu G, Balocco M, Marchese R, Murgia D, Melis M, Galanello R, Barella S, Matta G, Ruffinengo U, Bonuccelli U, Forni GL.

(Clinicaltrials.gov identifier: NTC00907283.)

Keywords: Deferiprone, Friedreich's ataxia, cerebral iron accumulation, pantothenate kinase-associated neurodegeneration, parkinsonism and focal dystonia, Magnetic resonance imaging, neurological examinations, Chelation treatment.

RNA-mediated transcriptional gene silencing in Friedreich ataxia

Current Opinion in Biotechnology, Volume 22, Supplement 1, September 2011, Page S16, European Biotechnology Congress 2011

Sanjay Bidichandani, Angela Castro and Yogesh Chutake

Department of Biochemistry & Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

You can find the abstract in the Strasbourg FARA conference summary.
http://www.curefa.org/_pdf/4thInternationalFAConferenceAbstracts.pdf

Assessment of neurological efficacy of idebenone in pediatric patients with Friedreich's ataxia: data from a 6-month controlled study followed by a 12-month open-label extension study.

J Neurol. 2011 Jul 22. [Epub ahead of print]

Meier T, Perlman SL, Rummey C, Coppard NJ, Lynch DR.
Santhera Pharmaceuticals, Liestal, Switzerland.

Keywords: idebenone, neurological function, ICARS, FARS, neurological rating scales, Friedreich's ataxia (FRDA), open-label extension study (IONIA-E), may offer a therapeutic benefit to pediatric FRDA patients.

A polymorphic miR-155 binding site in AGTR1 is associated with cardiac hypertrophy in Friedreich ataxia.

J Mol Cell Cardiol. 2011 Jul 12.

Kelly M, Bagnall RD, Peverill RE, Donelan L, Corben L, Delatycki MB, Semsarian C.
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, New South Wales, Australia; Sydney Medical School, University of Sydney, New South Wales, Australia.

Keywords:Friedreich ataxia (FRDA), expanded GAA trinucleotide repeat,frataxin gene (FXN), mitochondrial iron efflux, sensitivity to oxidative stress, variability in cardiac phenotype, genetic modifying factors, single nucleotide polymorphisms (SNPs), Renin-Angiotensin-Aldosterone system (RAAS), angiotensin-II type-1 receptor (AGTR1), angiotensin-converting enzyme (ACE), ACE2, left ventricular internal diameter in diastole (LVIDd), interventricular septal wall thickness (SWT), left ventricular mass (LVM), diastolic blood pressure, role of RAAS polymorphisms as modifiers of cardiac phenotype.

Structure-function analysis of Friedreich’s ataxia mutants reveals determinants for frataxin binding and activation of the Fe-S assembly complex

Biochemistry, Just Accepted Manuscript, DOI: 10.1021/bi200895k

Jennifer Bridwell-Rabb , Andrew M Winn , and David P. Barondeau

Keywords: Friedreich’s ataxia (FRDA), frataxin (FXN), GAA triplet repeat expansion, missense mutations, cysteine desulfurase, Fe-S cluster assembly activities, kcat/KM, NFS1, ISD11, ISCU2 (SDU), binding and allosteric activation of the Fe-S assembly complex.

Rim2, pyrimidine nucleotide exchanger, is needed for iron utilization in mitochondria

Biochem. J. (2011) Immediate Publication, doi:10.1042/BJ20111036

Heeyong Yoon, Yan Zhang, Jayashree Pain, Elise R. Lyver, Emmanuel Lesuisse, Debkumar Pain and Andrew Dancis
University of Pennsylvania, Philadelphia, U.S.A

Keywords: Mitochondria, iron, heme, Fe-S clusters, Mrs3, Mrs4, Yfh1, frataxin homolog, Rim2, mitochondrial carrier protein, pyrimidine exchange, promoting mitochondrial iron utilization.

Cardiac Dysfunction Causes Majority of Deaths in Friedreich's Ataxia

Original paper: Mortality in friedreich ataxia.

By: SHARON WORCESTER, Internal Medicine News Digital Network

Cardiac dysfunction remains the most common cause of death in patients with Friedreich’s ataxia, according to the findings of a retrospective study. read more

The Role of CyaY in Iron Sulfur Cluster Assembly on the E. coli IscU Scaffold Protein

PLoS ONE 6(7): e21992. doi:10.1371/journal.pone.0021992

OPEN ACCESS

Clara Iannuzzi1#, Salvatore Adinolfi1#, Barry D. Howes2#, Ricardo Garcia-Serres3#, Martin Clémancey4, Jean-Marc Latour5, Giulietta Smulevich2, Annalisa Pastore1

1 Medical Research Council National Institute for Medical Research, London, United Kingdom, 2 Dipartimento di Chimica “Ugo Schiff”, Università di Firenze, Sesto Fiorentino, Firenze, Italy, 3 Commissariat pour l'Energie Atomique, iRTSV/LCBM, Grenoble, France, 4 CNRS, UMR 5249, Grenoble, France, 5 Université Joseph Fourier, Grenoble, France

Full text PDF

Rapamycin reduces oxidative stress in frataxin deficient yeast cells

Mitochondrion, Article in Press, Accepted Manuscript, doi:10.1016/j.mito.2011.07.001

Carlo M.T. Marobbioa, 1, Isabella Pisanoa, 1, Vito Porcellia, Francesco M. Lasorsab and Luigi Palmieria, b.

a Laboratory of Biochemistry and Molecular Biology, Department of Pharmaco-Biology, University of Bari, Via E. Orabona 4, 70125 Bari, Italy
b CNR Institute of Biomembranes and Bioenergetics, Via Orabona 4, 70125 Bari, Italy

Keywords: Friedreich ataxia (FRDA), frataxin, mitochondria, antioxidant protection, mitochondrial damage, antioxidant idebenone, yeast frataxin knock-out model, iron accumulation, iron-sulphur cluster defects, high sensitivity to oxidative stress, reactive oxygen species (ROS), rapamycin, TOR kinases inhibitor, autophagy, mitophagy.

Long Range Regulation of Human FXN Gene Expression

PLoS ONE 6(7): e22001. doi:10.1371/journal.pone.0022001

Puspasari N, Rowley SM, Gordon L, Lockhart PJ, Ioannou PA, Delatycki MB, Sarsero JP
Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.

OPEN ACCESS
FULL TEXT PDF

Neurodegeneration with brain iron accumulation - Clinical Syndromes And Neuroimaging -

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Article in Press, doi:10.1016/j.bbadis.2011.06.016

Hyman M. Schipper,
Centre for Neurotranslational Research, Lady Davis Institute, Jewish General Hospital, Departments of Neurology & Neurosurgery and Medicine McGill University, Montreal, Quebec, Canada

Keywords: Iron, neurotoxic reactive oxygen species, body iron homeostasis, neurodegeneration with brain iron accumulation (NBIA), clinical syndromes and neuroimaging, magnetic resonance scanning, Friedreich ataxia (FA), pantothenate kinase 2-associated neurodegeneration (PKAN), PLA2G6-associated neurodegeneration (PLAN), FA2H-associated neurodegeneration (FAHN), Kufor-Rakeb disease (KRD), aceruloplasminemia, neuroferritinopathy.

Disabilità e terapia occupazionale nei pazienti con atassia di Friedreich

G Ital Med Lav Erg 2011; 33:2, 201-204

Irene Ciancarelli1,2, Vincenza Cofini1, Antonio Carolei3
1 Dipartimento di Medicina Interna e Sanità Pubblica - Università degli Studi di L’Aquila
2 Casa di cura di Riabilitazione Nova Salus - Trasacco
3 Clinica Neurologica - Dipartimento di Medicina Interna e Sanità Pubblica - Università degli Studi di L’Aquila

Keywords: Friedreich ataxia, occupational therapy, neuromotor
rehabilitation.

Overexpression of Human and Fly Frataxins in Drosophila Provokes Deleterious Effects at Biochemical, Physiological and Developmental Levels

PLoS ONE 6(7): e21017. doi:10.1371/journal.pone.0021017

OPEN ACCESS

Juan A. Navarro1#, José V. Llorens2,3#*, Sirena Soriano2, José A. Botella1, Stephan Schneuwly1, María J. Martínez-Sebastián2, María D. Moltó2,4

1 Institute of Zoology, University of Regensburg, Regensburg, Germany, 2 Departament de Genètica, Universitat de València, Burjassot, Valencia, Spain, 3 Instituto de Biomedicina, CSIC, Valencia, Spain, 4 CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental), Madrid, Spain

FULL TEXT PDF

Hyperexpansion of GAA repeats affects post-initiation steps of FXN transcription in Friedreich’s ataxia

Nucl. Acids Res. (2011) doi: 10.1093/nar/gkr542 First published online: July 10, 2011

Eunah Kim1,2, Marek Napierala1,2,* and Sharon Y. R. Dent1,2,*
1The Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center Science Park, Smithville, Texas 78957 and 2The Genes and Development Program, Graduate School of Biomedical Sciences and the Center for Cancer Epigenetics, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA

Keywords: Friedreich’s ataxia (FRDA), biallelic expansion of GAA repeats, frataxin (FXN) gene, chromatin modifications, chromatin immunoprecipitation, quantitative PCR, histone modifications, block of transition from initiation to a productive elongation.


Full Text pdf

Update on degenerative ataxias.

Curr Opin Neurol. 2011 Aug;24(4):339-45.

Klockgether T.
Department of Neurology, University Hospital Bonn and German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany.

Keywords: Degenerative ataxias, acquired ataxias, hereditary ataxias, nonhereditary degenerative ataxias, molecular genetic analysis, imaging studies, clinical assessment methods.

The Frataxin Homologue Fra Plays a Key Role in Intracellular Iron Channeling in Bacillus subtilis

ChemBioChem, 12: n/a. doi: 10.1002/cbic.201100190
Albrecht, A. G., Landmann, H., Nette, D., Burghaus, O., Peuckert, F., Seubert, A., Miethke, M. and Marahiel, M. A. (2011),

Keywords: Bacillus subtilis, frataxin, iron, metalloproteins, metalloproteomics

The Potential Investment Impact of Improved Access to Accelerated Approval on the Development of Treatments for Low Prevalence Rare Diseases

Orphanet Journal of Rare Diseases 2011, 6:49 (6 July 2011)

Miyamoto BE, Kakkis ED

OPEN ACCESS

FULL TEXT PDF

Accelerating access to treatments for rare diseases

Nature Reviews Drug Discovery 10, 475-476 (July 2011) | doi:10.1038/nrd3493
Marc Dunoyer

Changes in regulatory policy and legislative incentives to promote the development of drugs for rare diseases — orphan drugs — have led to increases in the number of orphan drug designations, but the rate of such products reaching the market remains frustratingly flat. This article highlights areas in which novel approaches could facilitate regulatory approval and access to treatments for rare diseases.

Gait Pattern in Inherited Cerebellar Ataxias.

Cerebellum. 2011 Jun 30. [Epub ahead of print]

Serrao M, Pierelli F, Ranavolo A, Draicchio F, Conte C, Don R, Di Fabio R, Lerose M, Padua L, Sandrini G, Casali C.
Department of Medical and Surgical Science and Biotechnologies, Sapienza University of Rome

Keywords: features of gait, ataxias, autosomal dominant (spinocerebellar ataxia, SCA1 or 2), recessive (Friedreich's ataxia, FRDA) ataxia, motion analysis system, gait kinematic, kinetic data, International Cooperative Ataxia Rating Scale (ICARS).

A gene expression phenotype in lymphocytes from Friedreich's Ataxia patients

Annals of Neurology, DOI: 10.1002/ana.22526

Giovanni Coppola MD, Ryan Burnett PhD, Susan Perlman MD, Revital Versano,Fuying Gao, Heather Plasterer PhD, Myriam Rai PhD, Francesco Saccá MD, Alessandro Filla MD, David R. Lynch MD PhD, James R. Rusche PhD, Joel M. Gottesfeld PhD, Massimo Pandolfo MD, Daniel H. Geschwind MD PhD.

Keywords: Biomarker; Gene expression; Friedreich's ataxia; Therapy

6th International Conference on Fe‐S Protein Biogenesis and Regulation

6th International Conference on
Fe‐S Protein Biogenesis and Regulation
22 – 25 August 2011 in Cambridge, UK

The Fitts task reveals impairments in planning and online control of movement in Friedreich ataxia: reduced cerebellar-cortico connectivity?

Neuroscience, doi:10.1016/j.neuroscience.2011.06.057, Available online 25 June 2011.

Louise A. Corben 1, 2, Nellie Georgiou-Karistianis 2, John L. Bradshaw 2, Darren R. Hocking 3, Andrew J. Churchyard 4 and Martin B. Delatycki 1, 5, 6

1 Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia
2 Experimental Neuropsychology Research Unit, School of Psychology and, Psychiatry, Monash University, Clayton, Victoria, Australia
3 Developmental Neuroscience and Genetic Disorders Laboratory, School of Psychology and Psychiatry, Monash University, Clayton, Victoria, Australia
4 Monash Neurology, Monash Medical Centre, Clayton, Victoria, Australia
5 Department of Clinical Genetics, Austin Health, Heidelberg, Victoria, Australia
6 Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia

KEYWORDS: Friedreich ataxia (FRDA), cognitive and/or psychomotor capacity, cerebellum, cortex, Fitts’ Law, preplanning of movement, online error detection and correction, prefrontal/anterior regions.

Case Report : Massive uterine leiomyoma in a patient with Friedreich’s ataxia: Is there a possible association?

Case Reports in Medicine, Received 26 May 2011; Accepted 24 June 2011

Evangelos Misiakos, Elli Siama, Dimitrios Schizas, Constantinos Petropoulos, Nick Zavras, Nikos Economopoulos, Alexandros Charalabopoulos, and Anastasios N. Macheras
University of Athens School of Medicine, Athens, Greece.

KEYWORDS: Friedreich’s ataxia, leiomyoma, intestinal obstruction, tumor excision, adhesionlysis, "neoplasms uncommon for their young age".

FULL TEXT PDF

Echocardiography: A Requisite Friend of the Cardiac Geneticist

Journal of the American Society of Echocardiography
Volume 24, Issue 7 , Pages 790-791, July 2011

Keywords: role of echocardiography in the early detection, frataxin, Friedreich's ataxia, noninvasive application.

To Be Targeted: Is the Magic Bullet Concept a Viable Option for Synthetic Nucleic Acid Therapeutics?

Human Gene Therapy. Ahead of print. doi:10.1089/hum.2011.065.

Manfred Ogris and Ernst Wagner.
Pharmaceutical Biotechnology, Ludwig Maximilians University, Munich 81377, Germany.

Keywords: Nucleic acids, genetic disorders, infectious diseases, cancer, viral vectors, synthetic delivery systems, receptor targeting of synthetic vectors, improve the specificity, increase the efficiency of nucleic acid delivery.

Correlation of frataxin content in blood and skeletal muscle endorses frataxin as a biomarker in Friedreich ataxia

Movement Disorders, 26: n/a. doi: 10.1002/mds.23789
Article first published online: 20 JUN 2011

Nachbauer, W., Wanschitz, J., Steinkellner, H., Eigentler, A., Sturm, B., Hufler, K., Scheiber-Mojdehkar, B., Poewe, W., Reindl, M. and Boesch, S

Keywords: Friedreich ataxia; frataxin; skeletal muscle; erythropoietin

Brain Implant Uses The Body's Skin Like A Conductor To Wirelessly Transmit The Brain's Neural Signals To Control A Computer

Medical News Today, Article Date: 17 Jun 2011
A brain implant developed at the University of Michigan uses the body's skin like a conductor to wirelessly transmit the brain's neural signals to control a computer, and may eventually be used to reactivate paralyzed limbs. Read more ....

Pricing and reimbursement of orphan drugs: the need for more transparency

Steven Simoens
Orphanet Journal of Rare Diseases 2011, 6:42doi:10.1186/1750-1172-6-42
Published: 17 June 2011

OPEN ACCES

Abstract (provisional)

Pricing and reimbursement of orphan drugs are an issue of high priority for policy makers, legislators, health care professionals, industry leaders, academics and patients. This study aims to conduct a literature review to provide insight into the drivers of orphan drug pricing and reimbursement. Although orphan drug pricing follows the same economic logic as drug pricing in general, the monopolistic power of orphan drugs results in high prices: a) orphan drugs benefit from a period of marketing exclusivity; b) few alternative health technologies are available; c) third-party payers and patients have limited negotiating power; d) manufacturers attempt to maximise orphan drug prices within the constraints of domestic pricing and reimbursement policies; and e) substantial R&D costs need to be recouped from a small number of patients. Although these conditions apply to some orphan drugs, they do not apply to all orphan drugs. Indeed, the small number of patients treated with an orphan drug and the limited economic viability of orphan drugs can be questioned in a number of cases. Additionally, manufacturers have an incentive to game the system by artificially creating monopolistic market conditions. Given their high price for an often modest effectiveness, orphan drugs are unlikely to provide value for money. However, additional criteria are used to inform reimbursement decisions in some countries. These criteria may include: the seriousness of the disease; the availability of other therapies to treat the disease; and the cost to the patient if the medicine is not reimbursed. Therefore, the maximum cost per unit of outcome that a health care payer is willing to pay for a drug could be set higher for orphan drugs to which society attaches a high social value. There is a need for a transparent and evidence-based approach towards orphan drug pricing and reimbursement. Such an approach should be targeted at demonstrating the relative effectiveness, cost-effectiveness and economic viability of orphan drugs with a view to informing pricing and reimbursement decisions.

FULL TEXT PDF

Neurodegeneration in friedreich's ataxia is associated with a mixed activation pattern of the brain. A fMRI study.

Hum Brain Mapp. 2011 Jun 14. doi: 10.1002/hbm.21319. [Epub ahead of print]

Ginestroni A, Diciotti S, Cecchi P, Pesaresi I, Tessa C, Giannelli M, Nave RD, Salvatore E, Salvi F, Dotti MT, Piacentini S, Soricelli A, Cosottini M, De Stefano N, Mascalchi M.
Department of Clinical Physiopathology, Radiodiagnostic Section, University of Florence, Florence, Italy.

Keywords: Friedreich's ataxia (FRDA), neurodegeneration, spinal cord, brain, MR Imaging (fMRI), left primary sensory-motor cortex, right cerebellum, left thalamus, right dorsolateral prefrontal cortex, globus pallidus, anterior cingulum, globus pallidus, regional neuronal damage, compensatory significance.

Friedreich’s ataxia variants I154F and W155R diminish frataxin-based activation of the iron-sulfur cluster assembly complex

Biochemistry, Just Accepted Manuscript, DOI: 10.1021/bi200666h
Publication Date (Web): June 14, 2011

Chi-Lin Tsai , Jennifer Bridwell-Rabb , and David P. Barondeau

Keywords: Friedreich’s ataxia (FRDA), frataxin (Fxn), GAA expansion, missense mutation, FRDA I154F, W155R variants, Nfs1, Isd11, Isu2, Fe-S cluster assembly machine, Fxn triggers sulfur transfer from Nfs1 to Isu.

New project: Identification of the E3 ligase that ubiquitinates frataxin

Principal researcher: Dr Roberto Testi, Department of Experimental Medicine,
University of Rome, ‘Tor Vergata,’ Italy

Keywods: frataxin, ubiquitin-proteasome system, ubiquitination, E3 ligase.

Sherman ku PhD working with friedreich's ataxia and induced pluripotent stem cells (iPSC)

Sigma bioblogs (3 Jun 2011)
Sherman Ku PhD interview
The Scripps Research Institute, Member of the Gottesfeld Lab

What is the focus of your research?
My research has focused on developing an induced pluripotent stem cell (iPSC) model of Friedreich’s ataxia (FRDA), which is ..... read more....

Edison Pharmaceuticals Announces Results of EPI-A0001 Phase 2A Double Blind Placebo Controlled 28-Day Clinical Trial in the Mitochondrial Disease- Friedreich's Ataxia

10th of June 2011

MOUNTAIN VIEW, Calif., June 10, 2011 /PRNewswire/ -- Edison Pharmaceuticals, Inc. announced today preliminary results obtained on a 28-day phase 2A clinical trial in Friedreich's ataxia.

EPI-A0001 did significantly improve neurological function as assessed by the Friedreich's Ataxia Rating Scale (FARS).

Read more

Emergency Use Protocol for EPI-743 in Acutely Ill Patients With Inherited Mitochondrial Respiratory Chain Disease Within 90 Days of End-of-Life Care

This study is currently recruiting participants.

First Received on June 7, 2011. Last Updated on June 9, 2011
Sponsor: Edison Pharmaceuticals Inc
Information provided by: Edison Pharmaceuticals Inc
ClinicalTrials.gov Identifier: NCT01370447


Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Transcranial Sonography Reveals Cerebellar, Nigral, and Forebrain Abnormalities in Friedreich’s Ataxia

Neurodegenerative Dis, (DOI: 10.1159/000327751)

Matthis Synofzik, Jana Godau, Tobias Lindig, Ludger Schöls, Daniela Berg
Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, and German Research Center for Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany

Keywords: Ataxia, Transcranial sonography, Friedreich’s ataxia, Imaging, Substantia nigra, Dentate nucleus, Iron, Cerebellum

Mortality in Friedreich Ataxia

Journal of the Neurological Sciences,Article in Press,
doi:10.1016/j.jns.2011.05.023

(J Neurol Sci. 2011 Aug 15;307(1-2):46-9. Epub 2011 Jun 8.)

Amy Y. Tsoua, Erin K. Paulsena, b, c, d, Sarah J. Lagedrosta, b, c, d, Susan L. Perlmane, Katherine D. Mathewsf, George R. Wilmotg, Bernard Ravinah, Arnulf H. Koeppeni, j and David R. Lyncha, b, c, d,

a Department of Neurology, University of Pennsylvania Medical School, United States
b Department of Pediatrics, University of Pennsylvania Medical School, United States
c Children's Hospital of Philadelphia, United States
d University of Pennsylvania Medical School, United States
e University of California Los Angeles, Los Angeles, CA, United States
f University of Iowa, Iowa City, IA, United States
g Emory University, Atlanta, GA, United States
h University of Rochester, Rochester, NY, United States
i VA Hospital, Albany, NY, United States

Keywords: Cerebellum; Sensory; Cardiomyopathy; Echocardiogram; Arrhythmia; Neurodegenerative disease

Repligen Reports Fourth Quarter ........ "RG2833 for Friedreich’s Ataxia"

9th of June 2011

RG2833 for Friedreich’s Ataxia
We are currently developing histone deacetylase class 1 inhibitors for the treatment of inherited neurodegenerative diseases such as Friedreich's ataxia. Friedreich's ataxia is caused by inadequate production of the protein frataxin which leads to degeneration of the nerves controlling muscle movements. Pending regulatory approval, we plan to initiate a Phase 1 study of RG2833 in Friedreich's ataxia patients in Europe by the end of the year. We are currently engaged in discussions with potential
pharmaceutical partners to evaluate whether partnering this program would increase the trajectory for global development and ultimately maximize the commercial potential of the asset.

Stem Cell Transplantation Offers 'Sea Of Opportunity' For Treating Debilitating Diseases

Medical News Today, Article Date: 09 Jun 2011

An article in the current issue of Technology & Innovation, Proceedings of the National Academy of Inventors ™ reports on the bright future and enormous need for stem cell therapeutics that may offer hope for those suffering from debilitating and deadly diseases. read more...

Edison Pharmaceuticals Announces FDA Grants EPI-743 Orphan Drug Designation

Medical News Today, Article Date: 09 Jun 2011

Edison Pharmaceuticals, Inc. announced the United States Food and Drug Administration has granted orphan drug designation to EPI-743 for treatment of inherited mitochondrial respiratory chain diseases. read more

Edison Pharmaceuticals ofrecerá un acceso ampliado al EPI-743 para la enfermedad mitocondrial

MOUNTAIN VIEW, California, 8 de junio de 2011 /PRNewswire/

La FDA autorizó un Programa de Acceso Ampliado con el propósito de administrar el fármaco en fase de investigación EPI-743 a los pacientes graves diagnosticados con enfermedades mitocondriales heredadas de la cadena respiratoria. leer más...

Edison Pharmaceuticals to Provide Expanded Access to EPI-743 for Mitochondrial Disease

7th of June 2011, Source: PR Newswire

MOUNTAIN VIEW, Calif., June 8, 2011 /PRNewswire/ -- Edison Pharmaceuticals, Inc. announced today that the U.S. Food and Drug Administration (FDA) has allowed an Expanded Access program to provide EPI-743 to seriously ill patients diagnosed with inherited respiratory chain diseases of the mitochondria. read more

Edison Pharmaceuticals élargit l'accès à EPI-743 pour les maladies mitochondriales

MOUNTAIN VIEW, Californie, June 8, 2011 /PRNewswire/ --

- La FDA autorise l'utilisation d'un nouveau médicament expérimental pour les cas menaçant le pronostic vital

Edison Pharmaceuticals, Inc. a aujourd'hui annoncé que la "Food and Drug Administration" américaine (la FDA) a autorisé un programme d'accès élargi pour offrir EPI-743 aux patients gravement malades ayant reçu un diagnostic de maladies héréditaires de la chaîne respiratoire mitochondriale. Les patients dont la maladie a été génétiquement confirmée comme ceux qui répondent à certains critères cliniques, en l'absence de confirmation génétique, sont tous éligibles. Lire plus.......

Edison Pharmaceuticals sorgt für erweiterten Zugang zu EPI-743 für mitochondriale Erkrankungen

MOUNTAIN VIEW, Kalifornien, June 8, 2011 /PRNewswire/ --

- FDA genehmigt Anwendung von Medikament in klinischer Testphase (Investigational New Drug) bei lebensbedrohlichen Befunden

Edison Pharmaceuticals, Inc. gab heute bekannt, dass die amerikanische Zulassungsbehörde für Lebens- und Arzneimittel, die US Food and Drug Administration (FDA), ein sogenanntes Expanded-Access-Programm genehmigt hat, durch das EPI-743 an schwerkranke Patienten mit diagnostizierter Störung der Atmungskette aufgrund mitochondrialer Erbkrankheiten verabreicht werden darf. Darunter fallen sowohl Patienten mit genetisch bestätigter Krankheit als auch Patienten, die bei fehlender genetischer Bestätigung spezifische klinische Kriterien erfüllen. Lesen Sie mehr ...

Differential Expression of PGC-1α and Metabolic Sensors Suggest Age-Dependent Induction of Mitochondrial Biogenesis in Friedreich Ataxia Fibroblasts

2011 PLoS ONE 6(6): e20666. doi:10.1371/journal.pone.0020666, OPEN ACCESS

García-Giménez JL, Gimeno A, Gonzalez-Cabo P, Dasí F, Bolinches-Amorós A, et al.

The induction of mitochondrial biogenesis in FRDA may be a consequence of the mitochondrial impairment associated with disease evolution. The increase of ROS and the involvement of the oxidative phosphorylation may be an early event in the cell pathophysiology of frataxin deficiency, whereas increase of mitochondriogenic response might be a later phenomenon associated to the individual age and natural history of the disease, being more evident as the patient age increases and disease evolves. This is a possible explanation of heart disease in FRDA.

FULL TEXT PDF

Clinical trials for stem cell therapies

BMC Medicine 2011, 9:52doi:10.1186/1741-7015-9-52
OPEN ACCESS

Alan Trounson, Rahul G Thakar, Geoff Lomax and Don Gibbons.
California Institute for Regenerative Medicine, San Francisco, USA

In recent years, clinical trials with stem cells have taken the emerging field in many new directions. While numerous teams continue to refine and expand the role of bone marrow and cord blood stem cells for their vanguard uses in blood and immune disorders, many others are looking to expand the uses of the various types of stem cells found in bone marrow and cord blood, in particular mesenchymal stem cells, to uses beyond those that could be corrected by replacing cells in their own lineage. Early results from these trials have produced mixed results often showing minor or transitory improvements that may be attributed to extracellular factors. More research teams are accelerating the use of other types of adult stem cells, in particular neural stem cells for diseases where beneficial outcome could result from either in-lineage cell replacement or extracellular factors. At the same time, the first three trials using cells derived from pluripotent cells have begun.

FULL TEXT PDF

Characterization of poly (rc) binding protein (pcbp2) and frataxin

Wayne State University Theses. Paper 71.

Ghimire-Rijal, Sudipa, (2011). Wayne State University Theses. Paper 71.

Keywords: Iron, cofactor, cellular iron homeostasis, Poly (rC) Binding Protein family, iron chaperone, PCBP2, dimeric protein.

The cerebellar component of Friedreich's ataxia.

Acta Neuropathol. 2011 Jun 3. [Epub ahead of print]

Koeppen AH, Davis AN, Morral JA.
Research Service (151), Veterans Affairs Medical Center, USA

Keywords: frataxin, Friedreich's ataxia (FRDA),progressive atrophy, dentate nucleus (DN), intact Purkinje cell somata, dendrites, severe loss of large NSE-reactive neurons, Small neurons remained intact, basket fibers, Golgi neurons, Golgi axonal plexuses, γ-aminobutyric acid (GABA), GABA-ergic terminals.

Utilisation of Advance Motor Information is Impaired in Friedreich Ataxia.

Cerebellum. 2011 Jun 2. [Epub ahead of print]

Corben LA, Delatycki MB, Bradshaw JL, Churchyard AJ, Georgiou-Karistianis N.
Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Royal Children's Hospital, Australia.

Keywords: Friedreich ataxia (FRDA), motor planning ability, age of disease onset, motor cognition, cerebellar impairment, cerebro-ponto-cerebello-thalamo-cerebral loops, direct primary cortical pathology.

Milestones in ataxia.

Mov Disord. 2011 May;26(6):1134-41. doi: 10.1002/mds.23559.

Klockgether T, Paulson H.

Department of Neurology, University Hospital Bonn, Bonn, Germany; German Center for Neurodegenerative Disorder (DZNE), Bonn, Germany

Keywords: genetic and molecular basis of ataxias, pathogenesis, spinocerebellar ataxias, ataxia telangiectasia, Friedreich ataxia, protein aggregation, failure of protein homeostasis, perturbations in ion channel function, defects in DNA repair, mitochondrial dysfunction.

Development of benzoquinoquinoxaline derivatives as triplex-specific probes: Recognition of DNA structures at repeats sequences

Bergquist, Helen (Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics)

Doctoral thesis, 2011-05-10
ISBN: 978-91-7447-296-7

Keywords: Triplex, H-DNA, BQQ, BQQ-OP, BQQ-Bodipy, triplet repeat, DNA, non-B-DNA, pkd1, frataxin, Friedreich's ataxia

Automatic identification of gait events using an instrumented sock

In addition of the potential of using textile-based transducers in future devices, I also think in a possible help to assess gait objectively (to help improve the measurement of the ICARS scale)

Journal of NeuroEngineering and Rehabilitation 2011, 8:32 doi:10.1186/1743-0003-8-32
Published: 27 May 2011, OPEN ACCESS

Stephen J Preece, Laurence P J Kenney, Matthew J Major, Tilak Dias, Edward Lay and Bosco T Fernandes

Background
Textile-based transducers are an emerging technology in which piezo-resistive properties of materials are used to measure an applied strain. By incorporating these sensors into a sock, this technology offers the potential to detect critical events during the stance phase of the gait cycle. This could prove useful in several applications, such as functional electrical stimulation (FES) systems to assist gait.
Methods
We investigated the output of a knitted resistive strain sensor during walking and sought to determine the degree of similarity between the sensor output and the ankle angle in the sagittal plane. In addition, we investigated whether it would be possible to predict three key gait events, heel strike, heel lift and toe off, with a relatively straight-forward algorithm. This worked by predicting gait events to occur at fixed time offsets from specific peaks in the sensor signal.
Results
Our results showed that, for all subjects, the sensor output exhibited the same general characteristics as the ankle joint angle. However, there were large between-subjects differences in the degree of similarity between the two curves. Despite this variability, it was possible to accurately predict gait events using a simple algorithm. This algorithm displayed high levels of trial-to-trial repeatability.
Conclusions
This study demonstrates the potential of using textile-based transducers in future devices that provide active gait assistance.

FULL TEXT PDF

Translating Stem Cell Research Into Therapies

Medical News Today, Article Date: 26 May 2011

The perspective on translating neural stem cell research into clinical therapeutics is part of a special issue of Neuron devoted to neural stem cells and neurogenesis

Original scientific paper: Translating Stem Cell Studies to the Clinic for CNS Repair: Current State of the Art and the Need for a Rosetta Stone
Karen Aboody, Alexandra Capela, Nilofar Niazi, Jeffrey H. Stern, and Sally Temple

FULL TEXT PDF

DNA Dynamics Is Likely to Be a Factor in the Genomic Nucleotide Repeats Expansions Related to Diseases

PLoS ONE 6(5): e19800. doi:10.1371/journal.pone.0019800
Alexandrov BS, Valtchinov VI, Alexandrov LB, Gelev V, Dagon Y, et al. 2011

OPEN ACCESS

Abstract
Trinucleotide repeats sequences (TRS) represent a common type of genomic DNA motif whose expansion is associated with a large number of human diseases. The driving molecular mechanisms of the TRS ongoing dynamic expansion across generations and within tissues and its influence on genomic DNA functions are not well understood. Here we report results for a novel and notable collective breathing behavior of genomic DNA of tandem TRS, leading to propensity for large local DNA transient openings at physiological temperature. Our Langevin molecular dynamics (LMD) and Markov Chain Monte Carlo (MCMC) simulations demonstrate that the patterns of openings of various TRSs depend specifically on their length. The collective propensity for DNA strand separation of repeated sequences serves as a precursor for outsized intermediate bubble states independently of the G/C-content. We report that repeats have the potential to interfere with the binding of transcription factors to their consensus sequence by altered DNA breathing dynamics in proximity of the binding sites. These observations might influence ongoing attempts to use LMD and MCMC simulations for TRS–related modeling of genomic DNA functionality in elucidating the common denominators of the dynamic TRS expansion mutation with potential therapeutic applications.

FULL TEXT PDF

Effects of Erythropoietin on Frataxin Levels and Mitochondrial Function in Friedreich Ataxia - a Dose-Response Trial.

Cerebellum. 2011 May 20. [Epub ahead of print]

Nachbauer W, Hering S, Seifert M, Steinkellner H, Sturm B, Scheiber-Mojdehkar B, Reindl M, Strasak A, Poewe W, Weiss G, Boesch S.
Source
Department of Neurology, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.

Keywords: Friedreich ataxia (FRDA), frataxin, recombinant human erythropoietin (rhuEPO), dose-response interactions, single doses (5,000, 10,000 and 30,000 IU), serum erythropoietin levels, iron metabolism, mitochondrial function, ataxia rating did not reveal clinical improvement, ferritin decrease.

Stem cell technology for neurodegenerative diseases

Annals of Neurology, (2011) DOI: 10.1002/ana.22487

J. Simon Lunn PhD, Stacey A. Sakowski PhD, Junguk Hur PhD, Eva L. Feldman MD PhD,
Department of Neurology – University of Michigan, Ann Arbor, MI

Keywords: stem cell technologies, neurodegenerative diseases, stem cell therapies.

First step in a possible therapeutic approach using stem cells for Friedreich's ataxia

Sent by: Dr. Jonathan Jones, Neuroscience Institute, Miguel Hernández University, San Juan, Alicante, 03550 SPAIN

The Experimental Embryology lab in the Neuroscience Institute in Alicante, Spain, is researching on the possible use of bone marrow and/or adipose tissue-derived mesenchymal stem cells for the treatment of Friedreich's Ataxia. To this end, stem cells are injected intrathecally into the spinal cord of a FA mouse model, where the cells will attach to the dorsal root ganglion. Here, the cells will release trophic factors to protect the large sensory neurons from death, which is reflected in an improvement in motor skills. This is a first step in a possible therapeutic approach using stem cells for Friedreich's ataxia.

___________________________________________________________________________

More information about the project (Spanish)

Research Fellowship: Visual dissection of GAA-mediated mechanisms of FRDA repression and identification of novel candidate factors involved in frataxin function

Principal Researchers: Dr Michele Lufino and Dr Richard Wade-Martins,
Department of Physiology, Anatomy and Genetics, University of Oxford.

Developing a Balanced Business Model for Gene Therapy

HUMAN GENE THERAPY 22:1–4 (June 2011),DOI: 10.1089/hum.2011.2504

"Research and outcomes like these give hope not only to patients, but to doctors who have spent years developing gene therapies for diseases that have not responded as well to traditional therapy.The promise shown by the results also create hope that gene therapy can finally emerge as avibrant segment, after years in which biopharma companies, physicians, insurers, and government regulators have struggled to develop a sustainable business model."

Full text pdf

Friedreich's Ataxia: Phenotypic variability: 4-case reports (two sets of siblings)

Published in Fisioterapia. 2010;32:190-4. - vol.32 núm 04
Gago Fernández, I.; Seco Calvo, J.

Keywords: clinical phenotype, Friedreich's Ataxia, activities of Daily Life, Health Quality of Life, Questionnaire of Health, multisystem involvement, phenotypic variability.

An investigation to determine the efficacy and safety of lentivirus mediated FXN gene delivery for the correction of Friedreich ataxia

Principal researchers: Dr Mark Pook and Dr Michael Themis Brunel University,
Uxbridge, UK

In children with Friedreich ataxia, muscle and ataxia parameters are associated

Developmental Medicine & Child Neurology, 53: 529–534. doi: 10.1111/j.1469-8749.2011.03931.x (Article first published online: 16 MAY 2011)

SIVAL, D. A., POUWELS, M. E., VAN BREDERODE, A., MAURITS, N. M., VERSCHUUREN-BEMELMANS, C. C., BRUNT, E. R., DU MARCHIE SARVAAS, G. J., VERBEEK, R. J., BROUWER, O. F. and VAN DER HOEVEN, J. H. (2011).

Keywords: Friedreich ataxia (FRDA), ataxia, International Cooperative Ataxia Rating Scale (ICARS), muscle weakness, muscle ultrasound density (MUD), muscle force, sensory evoked potentials, and ICARS scores, FXN gene analysis, persistently absent sensory evoked potentials, leg muscle force.

Next Generation Gamers: Computer Games Aid Recovery From Stroke

Could be also useful in the FA rehabilitation?

Medical News Today. 15 May 2011
Computer games are not just for kids. New research published in Journal of NeuroEngineering and Rehabilitation, a BioMed Central open access journal, shows that computer games can speed up and improve a patient's recovery from paralysis after stroke.

Scientific paper:
"Robotically Facilitated Virtual Rehabilitation of Arm Transport Integrated With Finger Movement in Persons with Hemiparesis"
Alma S Merians, Gerard G Fluet, Qinyin Qiu, Soha Saleh, Ian Lafond, Amy Davidow and Sergei V Adamovich
Journal of NeuroEngineering and Rehabilitation (in press)