Effects of Long-Term Pioglitazone Treatment on Peripheral and Central Markers of Aging

"Currently in France is running a trial with Pioglitazone . Although the subject matter of the article is not about the FA, get more information about this drug is interesting."

OPEN ACCES

PLoS ONE 5(4): e10405. doi:10.1371/journal.pone.0010405

Eric M. Blalock^1#, Jeremiah T. Phelps^1#, Tristano Pancani¹, James L. Searcy¹, Katie L. Anderson¹, John C. Gant¹, Jelena Popovic¹, Margarita G. Avdiushko², Don A. Cohen², Kuey-Chu Chen¹, Nada M. Porter¹, Olivier Thibault^1*

1 Department of Molecular and Biomedical Pharmacology, University of Kentucky Medical Center, Lexington, Kentucky, United States of America, 2 Department of Microbiology and Immunology, University of Kentucky Medical Center, Lexington, Kentucky, United States of America

Abstract

Thiazolidinediones (TZDs) activate peroxisome proliferator-activated receptor gamma (PPARγ) and are used clinically to help restore peripheral insulin sensitivity in Type 2 diabetes (T2DM). Interestingly, long-term treatment of mouse models of Alzheimer's disease (AD) with TZDs also has been shown to reduce several well-established brain biomarkers of AD including inflammation, oxidative stress and Aβ accumulation. While TZD's actions in AD models help to elucidate the mechanisms underlying their potentially beneficial effects in AD patients, little is known about the functional consequences of TZDs in animal models of normal aging. Because aging is a common risk factor for both AD and T2DM, we investigated whether the TZD, pioglitazone could alter brain aging under non-pathological conditions.

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Carbamylated erythropoietin increases frataxin independent from the erythropoietin receptor

European Journal of Clinical Investigation, Early View (Articles online in advance of print), Published Online: 28 Apr 2010
BRIEF COMMUNICATION

Brigitte Sturm*, Melissa Helminger*, Hannes Steinkellner*, Mohammad Mehdi Heidari*,†, Hans Goldenberg* and Barbara Scheiber-Mojdehkar*
*Medical University of Vienna, Vienna, Austria , † Yazd University, Yazd, Iran

KEYWORDS: Carbamylated erythropoietin • erythropoietin receptor • frataxin • Friedreich's ataxia • nonerythropoietic erythropoietin • recombinant human erythropoietin

Dysarthria in Friedreich's Ataxia: A Perceptual Analysis.

Folia Phoniatr Logop. 2010;62(3):97-103. Epub 2010 Apr 29.

Folker J, Murdoch B, Cahill L, Delatycki M, Corben L, Vogel A.

The University of Queensland, Brisbane, Qld., Australia.

Keywords: speech intelligibility,  dysarthria severity,  Friedreich's ataxia (FRDA), clinical factors.

'Epigenetic' Concepts Offer New Approach To Degenerative Disease

Medical News Today, Article Date: 28 Apr 2010 - 5:00 PDT

In studies on cancer, heart disease, neurological disorders and other degenerative conditions, some scientists are moving away from the "nature versus nurture" debate, and are finding you're not a creature of either genetics or environment, but both - with enormous implications for a new approach to health.  read more

Molecular Perspective Review of Biochemical Role of Nucleobases Modified by Oxidative Stress

COMPUTATIONAL METHODS IN SCIENCE AND TECHNOLOGY 16(1), XX-XX (2010)

Piotr Cysewski1,2
1 Department of Physical Chemistry, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń,
ul. Kurpińskiego 5, 85-950 Bydgoszcz, Poland
2Department of General Chemistry, University of Technology and Life Sciences in Bydgoszcz,
ul. Seminaryjna 3, 85-326 Bydgoszcz, Poland

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"Examples of cancer and non-cancer diseases, for which elevated levels of hydroxyl radical nucleobases were reported [12-15]. : .../... Elevated level in chromatin hydrolysates  (GA) in Friedreich' ataxia"

Folate regulation of axonal regeneration in the rodent central nervous system through DNA methylation

J Clin Invest. doi:10.1172/JCI40000.

Bermans J. Iskandar¹, Elias Rizk¹, Brenton Meier¹, Nithya Hariharan¹, Teodoro Bottiglieri², Richard H. Finnell³, David F. Jarrard⁴, Ruma V. Banerjee⁵, J.H. Pate Skene⁶, Aaron Nelson¹, Nirav Patel¹, Carmen Gherasim⁵, Kathleen Simon¹, Thomas D. Cook⁷ and Kirk J. Hogan⁸

¹Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin, USA.
²Baylor Research Institute, Institute of Metabolic Disease, Dallas, Texas, USA.
³Texas Institute for Genomic Medicine, Houston, Texas, USA.
⁴Department of Surgery, University of Wisconsin, Madison, Wisconsin, USA.
⁵Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, USA.
⁶Department of Neurobiology, Duke University Medical Center, Durham, North Carolina, USA.
⁷Department of Biostatistics and
⁸Department of Anesthesiology, University of Wisconsin, Madison, Wisconsin, USA. 

 Keywords: folate supplementation, neurodegenerative and neuropsychiatric disorders, afferent spinal neurons, DNA methylation, axonal regeneration, epigenetic mechanism contributing to neurorepair, promote regeneration.

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See the related Commentary:

J. Clin. Invest. doi:10.1172/JCI40764.

Neuronal injury: folate to the rescue?

Golo Kronenberg, Matthias Endres

Understanding the molecular mechanisms of Friedreich Ataxia to develop therapeutic approaches.

Hum Mol Genet. 2010 Apr 22.

Stéphane Schmucker^a,d,e and Hélène Puccio^{a,b,c,d,e,* a} IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), 1 rue Laurent Fries, BP10142, Illkirch, F-67400 France ; ^b Inserm, U596, Illkirch, F-67400 France ; ^c CNRS, UMR7104, Illkirch, F-67400 France ; ^d Université Louis Pasteur, Strasbourg, F-67000, France ; ^e Collège de France, Chaire de génétique humaine, Illkirch, F-67400 France

Keywords:  Friedreich ataxia, neurodegenerative disease,  frataxin, iron sulfur cluster (ISC), cellular iron dysregulation, potential novel therapeutic approaches.

[Usefulness of electromyography in diagnostics of the neuro-muscular diseases]

Przegl Lek. 2009;66(11):913-9.

Kroczka S, Steczkowska M, Kaciński M.

Katedry Neurologii Dzieci i Młodziezy, Uniwersytet Jagielloński Collegium Medicum, Kraków. neupedkr@cm-uj.krakow.pl

[Article in Polish]

Keywords: Electrophysiological examinations, neuromuscular disorders, monitoring of the disease progress,  differential diagnosis.

Novel Strategy For Generating Induced Pluripotent Stem Cells For Clinical Use Is Safe And Efficient

Medical News Today,
Article Date: 17 Apr 2010 - 0:00 PDT

 A new technique for reprogramming human adult cells could greatly improve the safety and efficiency of producing patient-specific stem cells for use in a range of therapeutic applications to repair or replace damaged or diseased tissues.

Original paper full text pdf

Structural basis for Fe-S cluster assembly and tRNA thiolation mediated by IscS protein-protein interactions.

PLoS Biol. 2010 Apr 13;8(4):e1000354.

Rong Shi¹, Ariane Proteau¹, Magda Villarroya², Ismaïl Moukadiri², Linhua Zhang³, Jean-François Trempe¹, Allan Matte³, M. Eugenia Armengod², Miroslaw Cygler^1,3*

1 Department of Biochemistry, McGill University, Montréal, Québec, Canada, 2 Laboratorio de Genética Molecular, Centro de Investigación Príncipe Felipe, Valencia, Spain, 3 Biotechnology Research Institute, Montréal, Québec, Canada

OPEN ACCES

Highlight: "Our data support the role of frataxin as an iron donor for IscU to form the Fe-S clusters."

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A New Proposal For Achieving Neuronal Regeneration

Medical News Today, Article Date: 20 Apr 2010 - 2:00 PDT
Over the past four years, in the installations of the Faculty of Medicine, University of Cadiz, a group of researchers, headed by Doctor Carmen Estrada, has been studying neurogenesis the process of forming new neurons from mother cells in the adult mammal brain. The purpose of this research project is to contribute to the knowledge of this process with the object of finding some additional mechanism that would facilitate the treatment of pathologies of the central nervous system (CNS) that are suffered in consequence of neuronal death...

Frataxin, the mitochondrial iron chaperone for Fe-S cluster bioassembly

ProQuest, Dissertations & Theses

Jeremy David, Ph.D.,Wayne State University, 2010, 256 pages; AAT 3390960

Keywords: Iron, human disorders and diseases, Freidreich's Ataxia (FRDA),

frataxin, mitochondria, iron homeostasis, chaperone, Iron Sulfur Cluster (ISC),   ferrous iron, carboxylate ligands

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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

.../...

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.

.../...

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.

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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.

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

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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)

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Cell and gene therapies: moving from research to clinic

Journal of Translational Medicine 2010, 8:31 (29 March 2010)

Stroncek DF, Puri RK
1Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, Maryland, USA
2Center for Biologics Evaluation and Research, Food and Drug Administration,
Bethesda, Maryland, USA

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