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

OPEN ACCES

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.

FULL TEXT PDF

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.

A New Myohaptic Instrument to Assess Wrist Motion Dynamically

Sensors 2010, 10, 3180-3194; doi:10.3390/s100403180

Mario Manto 1, Niels Van Den Braber 2, Giuliana Grimaldi 3 and Piet Lammertse 2
1  FNRS, Neurologie ULB-Erasme, 808 Route de Lennik, 1070 Bruxelles, Belgium
2  Moog FCS, 2150 Ad Nieuw-Vennep, The Netherlands;
3  Neurologie, ULB Erasme, 808 Route de Lennik, 1070 Bruxelles, Belgium;


OPEN ACCES
Abstract: The pathophysiological assessment of joint properties and voluntary motion in neurological patients remains a challenge. This is typically the case in cerebellar patients, who exhibit dysmetric movements due to the dysfunction of cerebellar circuitry. Several tools have been developed, but so far most of these tools have remained confined to laboratories, with a lack of standardization. We report on a new device which combines the use of electromyographic (EMG) sensors with haptic technology for the dynamic investigation of wrist properties. The instrument is composed of a drivetrain, a haptic controller and a signal acquisition unit. Angular accuracy is 0.00611 rad, nominal torque is 6 N·m, maximal rotation velocity is 34.907 rad/sec, with a range of motion of –1.0472 to +1.0472 rad. The inertia of the motor and handgrip is 0.004 kg·m2. This is the first standardized myohaptic instrument allowing the dynamic characterization of wrist properties, including under the condition of artificial damping. We show that cerebellar patients are unable to adapt EMG activities when faced with an increase in damping while performing fast reversal movements. The instrument allows the extraction of an electrophysiological signature of a cerebellar deficit.

Keywords: movement; sensor; myohaptic; damping; ataxia

FULL TEXT PDF

Long intronic GAA repeats causing Friedreich ataxia impede transcription elongation

EMBO Molecular Medicine DOI 10.1002/emmm.201000064
Volume 2 Issue 4,;Pages 120-129, Published Online: 1 Apr 2010

Tanel Punga, Marc Bühler

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland

Keywords: epigenetics • Friedreich ataxia (FRDA) • heterochromatic gene silencing • histone modification • triplet repeat expansion disorder (TRED)

FULL TEXT PDF