Projets de traitement des maladies d’Alzheimer et de Friedreich

Very encouraging news, Dr. Patrick Aubourg, will work with FA, this Dr. has already succeeded in stopping the evolution of Adrenoleukodystrophy(ALD), also called "Siemerling-Creutzfeldt Disease in some children, with autologous trasplant of bone marrow stem cells, with cells corrected by gene therapy

Patrick Aubourg,  Docteur en médecine et Professeur à l’Université Paris-Descartes. Il dirige l'Unité Inserm Génétique et biothérapies des maladies dégénératives et prolifératives du système nerveux, à l’Hôpital Saint-Vincent de Paul.

Le Grand Prix scientifique 2010 de la Fondation Simone et Cino del Duca a été attribué au Professeur Patrick Aubourg.

Dans l’ataxie de Friedreich, l’objectif est d’introduire le gène fonctionnel de la frataxine, une protéine essentielle au fonctionnement du cervelet, localisée dans des organites cellulaires précis : les mitochondries. Le manque de frataxine dans ces organites entraîne la perturbation d'une structure indispensable à leur bon fonctionnement, et tardivement une accumulation de fer. L’équipe de Patrick Aubourg teste deux nouveaux vecteurs viraux de thérapie génique pour déterminer lequel, après injection intra-veineuse, a la plus grande efficacité pour faire exprimer la frataxine non seulement dans les cellules du cervelet, mais aussi dans le cœur et la moelle épinière.

PRESS RELEASE IN ENGLISH 

More information about ADL Treatment:

Successful treatment of adrenoleukodystrophy by transplantation of ..

2 Children Suffering From Adrenoleukodystrophy Saved Thanks To The ELA Association

Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy
Science 6 November 2009: Vol. 326. no. 5954, pp. 818 - 823, DOI: 10.1126/science.1171242

Astrocyte-Specific Overexpression of Nrf2 Protects Striatal Neurons from Mitochondrial Complex II Inhibition

Toxicol Sci. 2010 Jun;115(2):557-68. Epub 2010 Mar 8.

Calkins MJ, Vargas MR, Johnson DA, Johnson JA.

Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin 53705, USA.

Variations of frataxin protein levels in normal individuals.

Neurol Sci. 2010 May 27.

Boehm T, Scheiber-Mojdehkar B, Kluge B, Goldenberg H, Laccone F, Sturm B.

Department of Medical Chemistry, Medical University of Vienna, Waehringerstr. 10, 1090, Vienna, Austria.

Keywords: Friedreich's ataxia (FRDA),  frataxin (FXN),  50 healthy Austrian people,  lymphocytes from blood, ELISA.

Graves' disease in a patient with Friedreich's ataxia and diabetes mellitus.

Curr Opin Pediatr. 2010 May 21. [Epub ahead of print]

Schweiger B, Klingensmith GJ, Wadwa RP.

aThe Children's Hospital, USA bBarbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, USA.

Assessment of Brain White Matter Fiber Bundle Atrophy in Patients with Friedreich Ataxia

Radiology, 255, 882-889. June 2010, doi: 10.1148/radiol.10091742
  
Elisabetta Pagani, MPhil, Andrea Ginestroni, MD,Riccardo Della Nave, MD, PhD,Federica Agosta, MD,Fabrizio Salvi, MD,Giuseppe De Michele, MD,Silvia Piacentini, MD,Massimo Filippi, MD and Mario Mascalchi, MD, PhD

Mitochondrial iron trafficking and the integration of iron metabolism between the mitochondrion and cytosol.

Proc Natl Acad Sci U S A. 2010 May 21.

Richardson DR, Lane DJ, Becker EM, Huang ML, Whitnall M, Rahmanto YS, Sheftel AD, Ponka P.

Iron Metabolism and Chelation Program, Discipline of Pathology, University of Sydney, NSW 2006, Australia.

Repligen Receives Orphan Drug Designation from the FDA for RG2833 for Friedreich's Ataxia

WALTHAM, Mass., May 24 /PRNewswire-FirstCall/ -- Repligen Corporation (Nasdaq: RGEN) announced today that the Office of Orphan Products Development of the Food and Drug Administration (FDA) has granted orphan drug designation to RG2833, a selective histone deacetylase 3 (HDAC-3) inhibitor for the treatment of Friedreich's ataxia.  Orphan drug designation qualifies Repligen to receive seven years of marketing exclusivity in the United States if the company is the first to obtain marketing approval for RG2833 for the treatment of Friedreich's ataxia.  This designation may also qualify Repligen to benefit from certain tax credits and a waiver of the company's obligation to pay the FDA application user fees for this product as required by the Prescription Drug User Fee Act. The U.S. Orphan Drug Act provides incentives for companies developing and marketing therapies for rare diseases, defined as those affecting fewer than 200,000 Americans.  There are approximately 15,000 people worldwide.......Read more

Iron Regulatory Proteins: From Molecular Mechanisms to Drug Development

Antioxidants & Redox Signaling. -Not available-, ahead of print. doi:10.1089/ars.2009.2983.

Stefania Recalcati,¹ Giorgio Minotti,² and Gaetano Cairo¹

¹Department of Human Morphology and Biomedical Sciences Città Studi, University of Milan, Milano, Italy.

²CIR and Drug Sciences, University Campus Bio-Medico and Fondazione Alberto Sordi-Research Institute on Aging, Roma, Italy.

Intracellular Redox Compartments: Mechanisms and Significances

Antioxidants & Redox Signaling. Ahead of print. doi:10.1089/ars.2009.3001.
Online Ahead of Print: May 17, 2010

Thomas Kietzmann

Department Chemistry/Biochemistry, University of Kaiserslautern, Kaiserslautern, Germany, and Department of Biochemistry, University of Oulu, Oulu, Finland.

Keywords:  reactive oxygen species (ROS),   act as signalling molecules,   hormones, growth factors, mechanical or chemical stress, mechanism of intracellular communication.

Human iron-sulfur cluster assembly, cellular iron homeostasis and disease.

Biochemistry. 2010 May 18. [Epub ahead of print]

Ye H, Rouault TA.

 Keyword: Iron sulfur (Fe-S) proteins, iron atoms, sulfur ligands, redox activity, enzymatic function, aconitase, succinate dehydrogenase, cellular iron homeostasis,  frataxin, GLRX5, ISCU, ABCB7, Friedreich's ataxia.

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Santhera’s MICONOS Trial with Catena®/Sovrima® in Friedreich’s Ataxia Misses Primary Endpoint

Liestal, Switzerland, May 20, 2010 – Santhera Pharmaceuticals (SIX: SANN) announced today that its MICONOS Phase III study evaluating Catena®/Sovrima® for the treatment of Frie-dreich’s Ataxia missed its primary endpoint. Trends towards improvement in the key neuro-logical endpoint were however identified by a meta-analysis of all Santhera’s Phase II and III studies in the same indication. MICONOS also confirmed that Catena®/Sovrima® is safe and well tolerated at doses of up to 2250 mg/day.

Pregnancy with Friedreich ataxia: a retrospective review of medical risks and psychosocial implications.

Am J Obstet Gynecol. 2010 May 15

Friedman LS, Paulsen EK, Schadt KA, Brigatti KW, Driscoll DA, Farmer JM, Lynch DR.

Departments of Neurology and Pediatrics, University of Pennsylvania School of Medicine, and Children's Hospital of Philadelphia.

Keywords: Friedreich ataxia (FRDA), pregnancy, spontaneous abortion, preeclampsia, preterm birth.

Neuroprotective Multifunctional Iron Chelators: From Redox-Sensitive Process to Novel Therapeutic Opportunities

Antioxidants & Redox Signaling. Ahead of print. doi:10.1089/ars.2009.2929.
Online Ahead of Print: May 17, 2010

Orly Weinreb, Tamar Amit, Silvia Mandel, Lana Kupershmidt, Moussa B.H. Youdim. 
Eve Topf Centers of Excellence for Neurodegenerative Diseases Research and Department of Pharmacology, Rappaport Family Research Institute, Technion-Faculty of Medicine, Haifa, Israel.

Keywords:  cytotoxic signals,   neurodegenerative brain, oxidative stress, inflammation, accumulation of iron,  iron chelators,  hydroxyl radical formation,  Fenton reaction, hypoxia-inducible factor-1α (HIF-1α), prolyl-4-hydroxylases (PHDs).

Potential Friedreich's Ataxia Drug Based on Gottesfeld Lab Work Poised to Start Clinical Trials

 NEWS & WIEW, Online weekly of the Scripps Research Institute, Vol 10. Issue 17 / May 17, 2010

"I'm as pleased as can be," said Gottesfeld. "It's wonderful news that our lab's work could be launching human trials for Friedreich's ataxia."

Ocular Motor Fixation Deficits in Friedreich Ataxia.

Cerebellum. 2010 May 15

Hocking DR, Fielding J, Corben LA, Cremer PD, Millist L, White OB, Delatycki MB.

Bruce Lefroy Center for Genetic Health Research, Murdoch Children's Research Institute, Parkville, Victoria, Australia.

Keywords: Friedreich ataxia (FRDA),  ocular motor abnormalities, fixation instability, saccadic dysmetria, vestibular dysfunction, gap overlap paradigm,  saccadic latency, cerebellum.

Ataxia with vitamin E deficiency: update of molecular diagnosis.

Neurol Sci. 2010 May 13.

Di Donato I, Bianchi S, Federico A.

Dipartimento di Scienze Neurologiche, Neurochirurgiche e del Comportamento, Università degli Studi di Siena, Viale Bracci, 53100, Siena, Italy.

Keyword: Ataxia with vitamin E deficiency (AVED),  autosomal recessive, neurodegenerative disease, TTPA gene, alpha-TTP, a cytosolic liver protein, alpha-tocopherol.

Repligen Files Investigational New Drug Application with FDA for First Drug Targeting the Core Genetic Defect of Friedreich's Ataxia

WALTHAM, Mass., May 13 /PRNewswire-FirstCall/ -- Repligen Corporation (Nasdaq: RGEN) announced today that it has filed an Investigational New Drug Application (IND) with the Food and Drug Administration (FDA) for a Phase 1 study of RG2833 .......

The role of echocardiographic deformation imaging in hypertrophic myopathies

Nat Rev Cardiol. 2010 May 11

Cikes M, Sutherland GR, Anderson LJ, Bijnens BH; Medscape.

University of Zagreb School of Medicine, Department of Cardiovascular Diseases, University Hospital Center Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia.

Keywords:  Echocardiography, hypertrophic myopathies,  ischemic heart disease, amyloidosis, Fabry disease,  Friedreich ataxia.

Low predisposition to instability of the Friedreich ataxia gene in Cuban population

T C Mariño ^a Y G Zaldivar ^b J M L Mesa ^b L A Mederos ^b R A Rodríguez ^b D A Gotay ^b R R Labrada ^b N C Ochoa ^b P MacLeod ^c L V Pérez ^b

  ^a Center of Medical Genetics, Calle Coliseo Esquina a Mártires, Avenida Cajigal Número 525F2, entre Luz y Progreso, Reparto Luz, Holguín, Cuba ,
  ^b Center for Research and Rehabilitation of Hereditary Ataxias 'Carlos Juan Finlay' (CIRAH), Holguín, Cuba ,
  ^c Division of Medical Genetics, Department of Pathology, Laboratory Medicine and Medical Genetics, Victoria General Hospital, Canada

Tufts Wins $9.5M Stimulus Grant for New Collaborative Cluster in Medford, Mass.

NEW YORK (GenomeWeb News) —

Tufts said its current collaborations include studies in model systems of diseases, such as fragile X mental retardation, Huntington's disease, and Friedreich's ataxia.

Altered lipid metabolism in a Drosophila model of Friedreich's ataxia

Hum. Mol. Genet. (10 May 2010), ddq183.

Juan A. Navarro, Elisabeth Ohmann, Diego Sanchez, Jose A. Botella, Gerhard Liebisch, Maria D. Molto, Maria D. Ganfornina, Gerd Schmitz, Stephan Schneuwly

Keywords:  Friedreich's ataxia (FRDA), mitochondrial protein frataxin,  Drosophila, lipid accumulation, peroxidation, oxidative stress, fatty acids,  glial cells, lipid peroxidation.

The Lost Boys: Neglected Generation Of Young Men With Duchenne Muscular Dystrophy Demand More Support

Medicals News Today,  Article Date: 11 May 2010

New research from the University of Bristol has found that the rights and needs of young men with Duchenne muscular dystrophy (DMD) - a life-limiting, inherited neuromuscular disease - are being severely restricted by the failure of many services to provide good planning and support.

CELLULAR STRESS RESPONSES, THE HORMESIS PARADIGM AND VITAGENES: NOVEL TARGETS FOR THERAPEUTIC INTERVENTION IN NEURODEGENERATIVE DISORDERS

http://www.liebertonline.com/doi/abs/10.1089/ars.2009.3074?mi=3b5d62&af=R&BeforeMonth=null&journalCode=null&issue=null&nh=20&AfterMonth=null&prevSearch=allfield%253A%2528%2522Friedreich%2527s%2522%2Bor%2B%2522Friedreich%2522%2Bor%2B%2522FRDA%2522%2529&discipline=null&group=null&restrict=all&result=true&filter=multiple&year=null&startPage=0&journal=null&AfterYear=null&favoriteJIds=null&sortBy=date&BeforeYear=null&doi=null&target=simple

Online Ahead of Editing: May 6, 2010

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

doi:10.1089/ars.2009.3074.  

Prof. Vittorio Calabrese,University of Catania, Department of Chemistry, Catania, Italy; Dr. Carolin Cornelius,University of Catania, Department of Chemistry, Catania, Italy; Prof. Albena T. Dinkova-Kostova,University of Dundee, The Biomedical Research Institute, Dundee, United Kingdom; Prof. Edward J. Calabrese

University of Massachusetts, Environmental Health Sciences Division, School of Public Health, Amherst, Massachusetts, United States; Dr. Mark Mattson, National Institute on Aging, Intramural Research Program, Baltimore, Maryland, United States;

Keywords:  chronic oxidative stress,  metabolic and neurodegenerative diseases,  hormesis,  neuroprotection, biological plasticity, therapeutic dose, pharmaceutical agents, sirtuin, Nrfs,  nitric oxide, carbon monoxide, H2S, mitochondrial redox signaling.

Mechanism elucidated for a rare disease

May 04 2010 
Scientists at the Friedrich Miescher Institute for Biomedical Research (FMI, part of the Novartis Research Foundation) have dissected one of the molecular mechanisms underlying Friedreich's ataxia. In doing so, they have shed new light on the pathogenic mechanism of the disease. These findings could lead to the development of new therapeutic approaches for what is, as yet, an incurable condition. The results of the study were recently published in the journal EMBO Molecular Medicine. 

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Caenorhabditis elegans as a model system to study intercompartmental proteostasis: Interrelation of mitochondrial function, longevity, and neurodegenerative diseases

Dev Dyn. 2010 May;239(5):1529-38. DOI 10.1002/dvdy.22292

Janine Kirstein-Miles, Richard I. Morimoto ^*
Department of Biochemistry, Molecular Biology and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois

Keywords:  proteostasis, eukaryotic cell,  mitochondria, cellular metabolism, organismal development,  lifespan,  neurodegenerative diseases, Friedreich's ataxia, Parkinson's disease.

Spinocerebellar ataxia: Patient and health professional perspectives on whether and how patents affect access to clinical genetic testing

Genetics in Medicine:

April 2010 - Volume 12 - Issue 4 - pp S83-S110

doi: 10.1097/GIM.0b013e3181d67e44

From the ¹Center for Public Genomics, Center for Genome Ethics, Law and Policy, Institute of Genome Sciences and Policy, Duke University, Curriculum in Neurobiology, University of North at Carolina Chapel Hill, Center for Genomics and Society at the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and ²Center for Genome Ethics, Law and Policy, Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina.

Robert Cook-Deegan, MD, Center for Genome Ethics, Law and Policy, Institute for Genome Sciences and Policy, Duke University, Box 90141, Durham, NC 27708. 

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Friedreich's Ataxia Cardiomyopathy: Case Based Discussion and Management Issues

Irish Medical Journal,  IMJ Online Paper.

A Hanley, R Corrigan, S Mohammad, B MacMahon
Monaghan General Hospital, Co Monaghan

Keywords: Cardiac involvement, Friedreich’s Ataxia, The most common symptoms are shortness of breath at rest and palpitations, ejection systolic murmur, heart sound, ECG abnormalities, Echo abnormalities, idebenone, Beta blockers, ACE inhibitors.