Translating the Genomics Revolution: The Need for an International Gene Therapy Consortium for Monogenic Diseases

Translating the Genomics Revolution: The Need for an International Gene Therapy Consortium for Monogenic Diseases. Jacques P Tremblay, Xiao Xiao, Annemieke Aartsma-Rus, Carlos Barbas, Helen M Blau, Adam J Bogdanove, Kym Boycott, Serge Braun, Xandra O Breakefield, Juan A Bueren, Michael Buschmann, Barry J Byrne, Michele Calos, Toni Cathomen, Jeffrey Chamberlain, Marinee Chuah, Kenneth Cornetta, Kay E Davies, J George Dickson, Philippe Duchateau, Terence R Flotte, Daniel Gaudet, Charles A Gersbach, Renald Gilbert, Joseph Glorioso, Roland W Herzog, Katherine A High, Wenlin Huang, Johnny Huard, J Keith Joung, Depei Liu, Dexi Liu, Hanns Lochmüller, Lawrence Lustig, Jeffrey Martens, Bernard Massie, Fulvio Mavilio, Jerry R Mendell, Amit Nathwani, Katherine Ponder, Matthew Porteus, Jack Puymirat, Jude Samulski, Shin’ichi Takeda, Adrian Thrasher, Thierry VandenDriessche, Yuquan Wei, James M Wilson, Steve D Wilton, John H Wolfe and Guangping Gao; Molecular Therapy (2013); 21 2, 266–268. doi:10.1038/mt.2013.4

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Jacques P Tremblay, Centre de Recherche du CHU and Department of Molecular Medicine, Université Laval, Quebec, Quebec, Canada, is working on gene therapy and protein replacement therapy in Friedreich's ataxia since long time.

See also: Translating the Genomics Revolution . (Jacques P Tremblay)

Emery and Rimoin's Principles and Practice of Medical Genetics

Chapter 23- Diagnostic Molecular Genetics. Wayne W. Grody, Joshua L. Deignan; Emery and Rimoin's Principles and Practice of Medical Genetics (Sixth Edition), 2013, Pages 1-31. http://dx.doi.org/10.1016/B978-0-12-383834-6.00030-6

FIGURE 23-9. PCR analysis of Friedreich ataxia GAA trinucleotide repeat expansion. Arrow indicates the size of PCR products generated from normal alleles. The samples shown are 1, normal; 2, homozygous expanded; and 3, heterozygous.

Chapter 101 – Iron Metabolism and Related Disorders. Kaveh Hoda, Christopher L. Bowlus, Thomas W. Chu, Jeffrey R. Gruen; Emery and Rimoin's Principles and Practice of Medical Genetics (Sixth Edition), 2013, Pages 1-41. http://dx.doi.org/10.1016/B978-0-12-383834-6.00106-3


Chapter 118 – The Hereditary Ataxias. Puneet Opal, Huda Zoghbi; Emery and Rimoin's Principles and Practice of Medical Genetics (Sixth Edition), 2013, Pages 1-32. http://dx.doi.org/10.1016/B978-0-12-383834-6.00125-7

Hereditary ataxias: overview.

Hereditary ataxias: overview. Jayadev S, Bird TD; Genet Med advance online publication 28 March 2013 Genetics in Medicine (2013); doi:10.1038/gim.2013.28.

Keywords: highly heterogeneous group, gait ataxia, incoordination of eye movements, speech, and hand movements, atrophy of the cerebellum, spinocerebellar ataxia, Friedreich, ataxia-telangiectasia, ataxia with oculomotor apraxia type 1, ataxia with oculomotor apraxia type 2, ataxia with vitamin E deficiency, cerebrotendinous xanthomatosis, Refsum, coenzyme Q10 deficiency.

Deferiprone and idebenone rescue frataxin depletion phenotypes in a Drosophila model of Friedreich’s ataxia

Deferiprone and idebenone rescue frataxin depletion phenotypes in a Drosophila model of Friedreich’s ataxia. Sirena Soriano, José V. Llorens, Laura B. Sobero, Lucía Gutiérrez, Pablo Calap-Quintana, M. Puerto Morales, M. Dolores Moltó, M. José Martínez-Sebastián. Gene, Available online 28 March 2013.

Keywords: Frataxin, aconitase, mitochondria, oxidative stress, life span, climbing capability

Edison Pharmaceuticals, Inc. signs licensing agreement with Dainippon Sumitomo Pharma Co., Ltd. for development & commercialization of orphan mitochondrial and adult central nervous system disease drugs

Edison Pharmaceuticals, Inc. signs licensing agreement with Dainippon Sumitomo Pharma Co., Ltd. for development & commercialization of orphan mitochondrial and adult central nervous system disease drugs.

MOUNTAIN VIEW, Calif., March 28, 2013 /PRNewswire/ -- Edison Pharmaceuticals today announced that it has entered into a research/development and commercialization agreement with Dainippon Sumitomo Pharma Co., Ltd. (DSP) for the development of EPI-743 and EPI-589 in Japan. read more...

Synthesis of Benzoquinone Antioxidants and a Bleomycin Disaccharide Library

Synthesis of Benzoquinone Antioxidants and a Bleomycin Disaccharide Library. Mathilakathu Madathil, Manikandadas (Author) / Hecht, Sidney M (Advisor) / Rose, Seth (Committee member) / Woodbury, Neal (Committee member) / Arizona State University (Publisher).; Doctoral Dissertation, ASU Electronic Dissertations and Theses (2013)

The synthesized 5-amino-3-tridecyl-1,4-benzoquinone antioxidants were tested for their ability to protect Friedreich's ataxia (FRDA) lymphocytes from induced oxidative stress. Some of the analogues synthesized conferred cytoprotection in a dose-dependent manner in FRDA lymphocytes at micromolar concentrations.


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Assessment of upper limb function in young Friedreich ataxia patients compared to control subjects using a new three-dimensional kinematic protocol

Assessment of upper limb function in young Friedreich ataxia patients compared to control subjects using a new three-dimensional kinematic protocol.
Nathalie Maurel, Amadou Diop, Arnaud Gouelle, Corinne Alberti, Isabelle Husson; Clinical Biomechanics, Available online 26 March 2013. http://dx.doi.org/10.1016/j.clinbiomech.2013.02.007

Keywords: Friedreich ataxia, Evaluation of upper limb function, Three-dimensional kinematic protocol, Reliability, Measurement errors, Discriminative ability.

Le phénotype atypique des maladies de Friedreich de début tardif et très tardif

Le phénotype atypique des maladies de Friedreich de début tardif et très tardif. C. Lecocq, K. Nguyen, J.-P. Azulay, A. Durr, M. Pandolfo, C. Tranchant, M. Anheim; Revue Neurologique, Volume 169, Supplement 2, April 2013, Pages A18-A19. http://dx.doi.org/10.1016/j.neurol.2013.01.036

Keywords: Friedreich, Lofa, vlofa, Ataxie cérébelleuse

The optic nerve: A “mito-window” on mitochondrial neurodegeneration

The optic nerve: A “mito-window” on mitochondrial neurodegeneration. Alessandra Maresca, Chiara la Morgia, Leonardo Caporali, Maria Lucia Valentino, Valerio Carelli; Molecular and Cellular Neuroscience, Volume 55, July 2013, Pages 62-76. http://dx.doi.org/10.1016/j.mcn.2012.08.004

Keywords: Mitochondrial disease, Optic atrophy, Mitochondrial functions, LHON, DOA, Friedreich ataxia, Retinal ganglion cells.

A New Assessment Tool for Ataxia Syndromes: The "STAND" (Scale To Assess Ataxia and Neurologic Dysfunction)

A New Assessment Tool for Ataxia Syndromes: The "STAND" (Scale To Assess Ataxia and Neurologic Dysfunction). Theresa Zesiewicz, Jessica Shaw, Israt Jahan, Kelly Sullivan, Kevin Allison, Joseph Staffetti, Patricia Greenstein, Clifton Gooch, Tuan Vu; AAN poster 2013

Objective: To evaluate a new ataxia rating scale, the STAND (Scale To assess Ataxia and Neurologic Dysfunction).

Families Push for New Ways to Research Rare Diseases

Families Push for New Ways to Research Rare Diseases . A version of this article appeared February 19, 2013, on page D1 in the U.S. edition of The Wall Street Journal, with the headline: Families Push For New Ways To Research Rare Diseases.

Parents with children who have rare and debilitating diseases are pushing to change how researchers develop medicines to treat the conditions.

The idea of sharing medical data from patients with rare diseases is gaining backing from public-health officials at the National Institutes of Health and the Food and Drug Administration

Companies and academic researchers, though, are often reluctant to cede control of what they consider proprietary information.

Epidemiology of Hereditary Ataxias in Spain: Hospital Discharge Registry and Population-Based Mortality Study

Epidemiology of Hereditary Ataxias in Spain: Hospital Discharge Registry and Population-Based Mortality Study. Alonso V., Villaverde-Hueso A., Hens M.J., Morales-Piga A., Abaitua I., Posada de la Paz M.; Neuroepidemiology 2013;41:13-19 (DOI:10.1159/000346275).

Keywords: Hereditary ataxias (HA), genetically heterogeneous rare diseases, morbimortality of HA, national death index (1981-2008), Friedreich's ataxia (45.4%), non-Friedreich group(54.6%).

Discovery of a Novel Small Molecule Inhibitor Targeting the Frataxin/Ubiquitin Interaction via Structure-Based Virtual Screening and

Discovery of a Novel Small Molecule Inhibitor Targeting the Frataxin/Ubiquitin Interaction via Structure-Based Virtual Screening and. Antonio Lavecchia, Carmen Di Giovanni, Carmen Cerchia, Annapina Russo, Giulia Russo, Ettore Novellino; J. Med. Chem., Just Accepted Manuscript. DOI: 10.1021/jm3017199

Keywords: Friedreich ataxia (FRDA), frataxin, ubiquitin–proteasomal pathway, residue K147, potential ubiquitin-binding domain.

Motor manifestations and basal ganglia output activity: The paradox continues

Motor manifestations and basal ganglia output activity: The paradox continues. Jose A. Obeso, J. Guridi, A. Nambu and A.R. Crossman. Movement Disorders. Article first published online: 14 MAR 2013 | DOI: 10.1002/mds.25358

KeR-EGI, a new index of gait quantification based on electromyography

KeR-EGI, a new index of gait quantification based on electromyography. Kristell Bervet, Manon Bessette, Lucille Godet, Armel Crétual; Journal of Electromyography and Kinesiology, Available online 16 March 2013. http://dx.doi.org/10.1016/j.jelekin.2013.02.006

Keywords: Gait analysis in adults, EMG-based gait quantification, Gait Deviation Index, Edinburgh Visual Gait Score

Hopes For Personalized Regenerative Medicine After Monkeys Receive Transplanted Brain Cells

Hopes For Personalized Regenerative Medicine After Monkeys Receive Transplanted Brain Cells. University of Wisconsin-Madison. (2013, March 17). Medical News Today. Retrieved from http://www.medicalnewstoday.com/releases/257709.php.

For the first time, scientists have transplanted neural cells derived from a monkey's skin into its brain and watched the cells develop into several types of mature brain cells, After six months, the cells looked entirely normal, and were only detectable because they initially were tagged with a fluorescent protein.



Citation: Induced Pluripotent Stem Cell-Derived Neural Cells Survive and Mature in the Nonhuman Primate Brain.
Marina E. Emborg, Yan Liu, Jiajie Xi, Xiaoqing Zhang, Yingnan Yin, Jianfeng Lu, Valerie Joers, Christine Swanson, James E. Holden, Su-Chun Zhang; Cell Reports - 14 March 2013 (OPEN ACCESS)

“Six sessions is a drop in the ocean”: an exploratory study of neurological physiotherapy in idiopathic and inherited ataxias

“Six sessions is a drop in the ocean”: an exploratory study of neurological physiotherapy in idiopathic and inherited ataxias. Gavin Daker-White, Julie Greenfield, John Ealing; Physiotherapy, Available online 15 March 2013, http://dx.doi.org/10.1016/j.physio.2013.02.001

Keywords: exploratory study, specialist neurological physiotherapy, improvements following therapy.

Bilateral cochlear implantation in Friedreich's ataxia: A case study.

Bilateral cochlear implantation in Friedreich's ataxia: A case study.. Frewin B, Chung M, Donnelly N., Cochlear Implants Int. 2013 Mar 9. [Epub ahead of print]

Keywords: Friedreich's ataxia (FRDA), sound detection thresholds, auditory pathways, Electrophysiological testing, cochlear nerve, pre-neural cochlear function, temporal processing, frequency discrimination, speech perception, ANSD, hearing loss.

A Pilot Study to Identify Asymptomatic Newborns at Risk for Friedreich Ataxia through the Analysis of Frataxin Levels in Dried-Blood-Spots

A Pilot Study to Identify Asymptomatic Newborns at Risk for Friedreich Ataxia through the Analysis of Frataxin Levels in Dried-Blood-Spots. Devin Oglesbee, Karen Sanders, Charles Kroll, Ramanath Majumdar, Amber McDonald, Grazia Isaya, Dimitar Gavrilov, Kimiyo Raymond, Silvia Tortorelli, Piero Rinaldo, Fred Lorey, Dietrich Matern. 2013 ACMG Annual Clinical Genetics meeting, Poster Presentations Phoenix Convention Center North Building.

Keywords: Friedreich ataxia, newborn screening pilot study, multiplex immunoassay, FXN levels, dried blood spots (DBS)

Frataxin Blood Level Contributes to a Positive Diagnosis of Friedreich Ataxia, a Case Report

Frataxin Blood Level Contributes to a Positive Diagnosis of Friedreich Ataxia, a Case Report; Lindsay Zetzsche, Ralitza Gavrilova, Devin Oglesbee; 2013 ACMG Annual Clinical Genetics meeting, Poster Presentations, Phoenix Convention Center North Building

Keywords: Friedreich ataxia, expansion allele in FXN, carrier for FRDA, blood protein frataxin level.

Complexes between two GAA Repeats within DNA introduced into Cos-1 cells.

Complexes between two GAA Repeats within DNA introduced into Cos-1 cells.. Krasilnikova MM.; Mob Genet Elements. 2012 Nov 1;2(6):267-271.

Keywords: Friedreich ataxia, GAA repeat, chromatin, genome instability, replication.

Heterochromatinization induced by GAA-repeat hyperexpansion in Friedreich's ataxia can be reduced upon HDAC inhibition by Vitamin B3

Heterochromatinization induced by GAA-repeat hyperexpansion in Friedreich's ataxia can be reduced upon HDAC inhibition by Vitamin B3 . Ping K. Chan, Raul Torres, Cihangir Yandim, Pui P. Law, Sanjay Khadayate, Marta Mauri, Crina Grosan, Nadine Chapman-Rothe, Paola Giunti, Mark Pook, and Richard Festenstein. Hum. Mol. Genet. first published online March 7, 2013 doi:10.1093/hmg/ddt115

Keywords: triplet repeat sequence (GAA.TTC), transcriptional repression, Frataxin gene (FXN), Friedreich's ataxia (FRDA), heterochromatinization, H3K9me3, H3K27me3, class III HDAC inhibitor vitamin B3 (nicotinamide), H3 and H4 histone acetylations, nicotinamide.

INDAGINI STRUTTURALI SU METALLOPROTEINE MEDIANTE DIFFRATTOMETRIA DEI RAGGI X

INDAGINI STRUTTURALI SU METALLOPROTEINE MEDIANTE DIFFRATTOMETRIA DEI RAGGI X. UNIVERSITÀ DEGLI STUDI DI NAPOLI “FEDERICO II”, TESI DI DOTTORATO IN SCIENZE CHIMICHE, DOTTORANDO: Dott.ssa Marisa Franzese

 The Ph. D. research activity, carried out in collaboration with Dr. Pastore (MRC, London) and Prof. Peisach (AECOM, New York) groups, was focused on structural analysis of the two different metalloproteins: 1) Hemoglobin; 2) Frataxin.

About Frataxin: 9-13, 119-134

Excessive motor overflow reveals abnormal inter-hemispheric connectivity in Friedreich ataxia.

Excessive motor overflow reveals abnormal inter-hemispheric connectivity in Friedreich ataxia. Low SC, Corben LA, Delatycki MB, Ternes AM, Addamo PK, Georgiou-Karistianis N.; J Neurol. 2013 Mar 5. [Epub ahead of print]

Keywords: force variability, motor overflow, Friedreich ataxia (FRDA), finger-pressing task, cortico-cerebellar disruption, motor control. inter-hemispheric activity.

A double-blind, randomized, placebo-controlled, clinical trial to test the efficacy of Epoetin alfa on physical performance of Friedreich Ataxia patients (FriEMax).

A double-blind, randomized, placebo-controlled, clinical trial to test the efficacy of Epoetin alfa on physical performance of Friedreich Ataxia patients (FriEMax). FARA, Clinical Trial Newsletter, March 2013

Expression profile of Yeast Frataxin Mutants

Expression profile of Yeast Frataxin Mutants. Moreno-Cermeño A, Alsina D, Cabiscol E, Ros J, Tamarit J. ; NCBI, Gene expression Omnibus (GEO), Public on Mar 06, 2013

Iron and Diabetes Risk

Iron and Diabetes Risk, Judith A. Simcox, Donald A. McClain; Cell Metabolism, Volume 17, Issue 3, 5 March 2013, Pages 329-341, http://dx.doi.org/10.1016/j.cmet.2013.02.007

Friedreich ataxia is associated with increased prevalence of type 2 diabetes. Abnormal IRP1 activity is seen in patients with Friedreich ataxia. It's thought frataxin is an iron chaperone or storage protein. IRP1 aconitase activity is decreased, while IRP binding to IREs is increased.

Iron and Copper in Mitochondrial Diseases

Iron and Copper in Mitochondrial Diseases, Wenjing Xu, Tomasa Barrientos, Nancy C. Andrews; Cell Metabolism, Volume 17, Issue 3, 5 March 2013, Pages 319-328


Fe-S cluster biogenesis may not be as severely affected in patients with Friedreich’s ataxia or animals carrying FXN mutations. Mitochondrial Fe accumulation has been reported (Lamarche et al., 1980; Puccio et al., 2001), but others suggest that it is an inconsistent and late finding (Bayot et al., 2011). However, Fxn-deficient mouse cells do show altered expression of genes that favor Fe uptake and mitochondrial import over Fe storage and export (Huang et al., 2009).

Friedreich's ataxia–associated GAA repeats induce replication-fork reversal and unusual molecular junctions

Friedreich's ataxia–associated GAA repeats induce replication-fork reversal and unusual molecular junctions. Cindy Follonier, Judith Oehler, Raquel Herrador & Massimo Lopes. Nature Structural & Molecular Biology (2013), Published online 03 March 2013, doi:10.1038/nsmb.2520

Keywords: Expansion of GAA/TTC repeats, mechanisms of replication interference and expansion, in vivo replication structures at GAA repeats, replication-associated intramolecular junctions, homopurine-homopyrimidine tracts, postreplicative mechanisms.

I JORNADA DE INVESTIGACIÓN EN ATAXIA DE FRIEDREICH

I JORNADA DE INVESTIGACIÓN EN ATAXIA DE FRIEDREICH

Screening for DNA-repair gene could predict rate of progress of Huntington’s disease, muscular dystrophy

Screening for DNA-repair gene could predict rate of progress of Huntington’s disease, muscular dystrophy, Polly Thompson The Hospital for Sick Children (Canada).

The genetic repair function is also important in Friedreich’s ataxia and at least 13 other neurodegenerative and neuromuscular diseases.

Citation: Tomé S, Manley K, Simard JP, Clark GW, Slean MM, et al. (2013) MSH3 Polymorphisms and Protein Levels Affect CAG Repeat Instability in Huntington's Disease Mice. PLoS Genet 9(2): e1003280. doi:10.1371/journal.pgen.1003280.

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Abnormal body iron distribution and erythropoiesis in a novel mouse model with inducible gain of iron regulatory protein (IRP)-1 function

Abnormal body iron distribution and erythropoiesis in a novel mouse model with inducible gain of iron regulatory protein (IRP)-1 function. D. Casarrubea, L. Viatte, T. Hallas, A. Vasanthakumar, R. S. Eisenstein, K. Schümann, M. W. Hentze, B. Galy. Journal of Molecular Medicine; March 2013, DOI 10.1007/s00109-013-1008-2.

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Inappropriately high IRP1 activity causes disturbed body iron distribution and erythropoiesis. This new mouse model further highlights the importance of appropriate IRP regulation in central organs of iron metabolism. Moreover, it opens novel avenues to study diseases associated with abnormally high IRP1 activity, such as Parkinson’s disease or Friedreich’s ataxia.

Les centres maladies rares en neurologie ont- ils changé les pratiques et la prise en charge dans les ataxies cérebelleuses héréditaires ?

Have centers of rare neurological diseases changed their practices and management of the hereditary cerebellar ataxias?. C. Tranchant; Revue Neurologique, Volume 169, Supplement 1, February 2013, Pages S23-S27

Les centres maladies rares en neurologie ont- ils changé les pratiques et la prise en charge dans les ataxies cérebelleuses héréditaires ?

Keywords: Recessive cerebellar ataxia, Dominant cerebellar ataxia, FXTAS, Friedreich's ataxia.

Paper in French