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