Erhaltene Reflexe, Propriozeption, SNAPs: trotzdem Friedreich-Ataxie - [Retained reflexes, proprioception, SNAPs: still Friedreich's ataxia]

Nervenarzt. 2010 Apr;81(4):442-3.
DOI: 10.1007/s00115-010-2946-3

 K. Dimitriadis^{1, 2}, S. Heck², M. Schubert¹ und T. Klopstock^{1, 2} 

(1)	Friedrich-Baur-Institut an der Neurologischen Klinik und Poliklinik, Klinikum der Universität München – Innenstadt, Ziemssenstraße 1a, 80336 München

(2)	Neurologische Klinik und Poliklinik, Klinikum der Universität München – Großhadern, München

 

Article in German

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Repligen Corporation - HDAC-3 Inhibitors for Friedreich's Ataxia

WALTHAM, Mass., April 16, 2010 /PRNewswire via COMTEX/ -- Repligen Corporation

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HDAC-3 Inhibitors for Friedreich's Ataxia
We are currently developing inhibitors of histone deacetylase 3 (HDAC-3) for the treatment of inherited neurodegenerative diseases such as Friedreich's ataxia.  Preclinical studies have shown that specific HDAC-3 inhibitors increase production of the protein frataxin which may have the potential to arrest disease progression in patients with Friedreich's ataxia.  We plan to file an Investigational New Drug Application (IND) for a Phase 1 human clinical study of RG2833 in healthy volunteers this quarter.

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Intermediate-Dose Idebenone and Quality of Life in Friedreich Ataxia

Pediatric Neurology
Volume 42, Issue 5, May 2010, Pages 338-342

n F. Brandsema MD^*, Derek Stephens MSc^†, Jessica Hartley MSc^‡ and Grace Yoon MD^{*, ‡}

^† Department of Child Health Evaluative Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Canada
^‡ Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada
^* Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Canada

Keywords: Idebenone, Friedreich ataxia, neurologic function, cardiac function, quality of life, 20 mg/kg per day, Pediatric Quality of Life Inventory,  International Cooperative Ataxia Rating Scale,  Activities of Daily Living Scale.

Health-Related Quality of Life in Children With Friedreich Ataxia

Pediatric Neurology
Volume 42, Issue 5, May 2010, Pages 335-337

Erin K. Paulsen BA^a, Lisa S. Friedman BA^a, Lauren M. Myers BA^a and David R. Lynch MD, PhD^{, a,}

^a Departments of Neurology and Pediatrics, University of Pennsylvania School of Medicine, and The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

Keywords:  health-related quality of life scales,  Friedreich ataxia, children,  PedsQL 4.0, Multidimensional Fatigue Scale.

Iron redistribution as a therapeutic strategy for treating diseases of localized iron accumulation.

Can J Physiol Pharmacol. 2010 Mar;88(3):187-96.

Kakhlon O, Breuer W, Munnich A, Cabantchik ZI.

Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Safra Campus at Givat Ram, Jerusalem 91904, Israel.

Keywords:  Iron,  mitochondria, neurodegeneration, frataxin, Friedreich's ataxia (FRDA), iron chelation, deferiprone (DFP), iron-relocating abilities,  cellular iron misdistribution.

Efficacy of Riluzole in Hereditary Cerebellar Ataxia - This study is currently recruiting participants.

www.clinicaltrials.gov

This study is currently recruiting participants.

Verified by S. Andrea Hospital, April 2010

First Received: April 7, 2010   Last Updated: April 14, 2010   

Sponsor:	S. Andrea Hospital
Information provided by:	S. Andrea Hospital
ClinicalTrials.gov Identifier:	NCT01104649

Coenzyme Q10-responsive ataxia: 2-Year-treatment follow-up

Movement Disorders,  Volume 9999, Issue 9999 , PagesNA -(Articles online in advance of print)
DOI. 10.1002/mds.23129


Merce Pineda, MD, PhD ^{1 2}, Raquel Montero, PhD ^{2 3}, Asuncion Aracil, MD ^{1 2}, Mar M. O'Callaghan, MD ^{1 2}, Ana Mas, MD ⁴, Carmen Espinos, PhD ², Dolores Martinez-Rubio, BS ^{2 5}, Francesc Palau, MD, PhD ^{2 5}, Placido Navas, PhD ^{2 6}, Paz Briones, PhD ^{2 7}, Rafael Artuch, MD, PhD ^{2 3 *1}Department of Pediatric Neurology, Hospital Sant Joan de Déu, Barcelona, Spain
²Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Spain
³Department of Clinical Biochemistry, Hospital Sant Joan de Déu, Barcelona, Spain
⁴Department of Pharmacy, Hospital Sant Joan de Déu, Barcelona, Spain
⁵Genetics and Medicine Molecular Unit, Instituto de Biomedicina de Valencia-CSIC, Valencia, Spain
⁶Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide, Sevilla, Spain
⁷Institut de Bioquímica Clínica, Hospital Clinic and CSIC, Barcelona, Spain

email: Rafael Artuch (rartuch@hsjdbcn.org)^*Correspondence to Rafael Artuch, Department of Clinical Biochemistry, Hospital Sant Joan de Déu, Passeig Sant Joan de Déu, 2, 08950 Esplugues, Barcelona, Spain

KEYWORDS: coenzyme Q₁₀ deficiency • mitochondrial disorders • ataxia • cerebellum • pediatric patients

Analysis of the factors influencing the cardiac phenotype in Friedreich's ataxia

Movement Disorders, Volume 9999, Issue 9999 , PagesNA - (Published Online: 13 Apr 2010)

Bheeshma Rajagopalan, FRCP ¹, Jane M. Francis, DCR(R) ², Fraser Cooke, MRCP ¹, L. V. Prasad Korlipara, MRCP ³, Andrew M. Blamire, PhD ¹, Anthony H.V. Schapira, FMedSci ³, Jason Madan, MSc ⁴, Stefan Neubauer, FRCP ², J. Mark Cooper, PhD ^{3 *1}Nuffield Department of Medicine, Department of Biochemistry, University of Oxford, Oxford, UK
²University of Oxford Centre for Clinical Magnetic Resonance Research, Oxford, UK
³Clinical Neurosciences, Institute of Neurology, UCL, London, UK
⁴Health Economics and Decision Science, ScHARR, University of Sheffield, Sheffield, UK

Funded by: Ataxia UK and the Medical Research Council

Keywords: Friedreich's ataxia (FRDA), cardiac hypertrophy, dilated cardiomyopathy, magnetic resonance imaging (MRI), LV mass, genetic mutation, GAA repeats, age of onset, effect of treatment.

PGC-1alpha Down-Regulation Affects the Antioxidant Response in Friedreich's Ataxia

PLoS ONE 5(4): e10025. doi:10.1371/journal.pone.0010025
Daniele Marmolino1, Mario Manto1,2, Fabio Acquaviva3, Paola Vergara3, Ajay Ravella1, Antonella Monticelli4, Massimo Pandolfo1*

1 Laboratoire de Neurologie Expérimentale, Université Libre de Bruxelles (ULB), Brussels, Belgium, 2 Fonds National de la Recherche Scientifique (FNRS), Brussels, Belgium, 3 Department of Cellular and Molecular Biology, University of Naples “Federico II”, Naples, Italy, 4 IEOS, Consiglio Nazionale delle Ricerche (CNR), Naples, Italy

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Background

Cells from individuals with Friedreich's ataxia (FRDA) show reduced activities of antioxidant enzymes and cannot up-regulate their expression when exposed to oxidative stress. This blunted antioxidant response may play a central role in the pathogenesis. We previously reported that Peroxisome Proliferator Activated Receptor Gamma (PPARγ) Coactivator 1-alpha (PGC-1α), a transcriptional master regulator of mitochondrial biogenesis and antioxidant responses, is down-regulated in most cell types from FRDA patients and animal models.
Methodology/Principal Findings

We used primary fibroblasts from FRDA patients and the knock in-knock out animal model for the disease (KIKO mouse) to determine basal superoxide dismutase 2 (SOD2) levels and the response to oxidative stress induced by the addition of hydrogen peroxide. We measured the same parameters after pharmacological stimulation of PGC-1α. Compared to control cells, PGC-1α and SOD2 levels were decreased in FRDA cells and did not change after addition of hydrogen peroxide. PGC-1α direct silencing with siRNA in control fibroblasts led to a similar loss of SOD2 response to oxidative stress as observed in FRDA fibroblasts. PGC-1α activation with the PPARγ agonist (Pioglitazone) or with a cAMP-dependent protein kinase (AMPK) agonist (AICAR) restored normal SOD2 induction. Treatment of the KIKO mice with Pioglitazone significantly up-regulates SOD2 in cerebellum and spinal cord.
Conclusions/Significance

PGC-1α down-regulation is likely to contribute to the blunted antioxidant response observed in cells from FRDA patients. This response can be restored by AMPK and PPARγ agonists, suggesting a potential therapeutic approach for FRDA.

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CNS-targeted gene therapy improves survival and motor function in a mouse model of spinal muscular atrophy

Published in Volume 120, Issue 4 (April 1, 2010)
J Clin Invest. 2010;120(4):1253–1264. doi:10.1172/JCI41615.

Marco A. Passini, Jie Bu, Eric M. Roskelley, Amy M. Richards, S. Pablo Sardi, Catherine R. O’Riordan, Katherine W. Klinger, Lamya S. Shihabuddin and Seng H. Cheng

Genzyme Corporation, Framingham, Massachusetts.