Current and emerging treatment options in the management of Friedreich ataxia

Neuropsychiatric Disease and Treatment, Published Date July 2010 , Volume 2010:6 Pages 491 - 499

Michelangelo Mancuso, Daniele Orsucci, Anna Choub, Gabriele Siciliano
Department of Neuroscience, Neurological Clinic, University of Pisa, Pisa, Italy

Keywords: Friedreich ataxia (FRDA), Oxidative damage, mitochondria, antioxidant protection, idebenone, cardiac hypertrophy, frataxin gene transcription, iron-chelating therapies, erythropoietin, histone deacetylase inhibitors, gene-based strategies.

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EMBL scientists identify proteins that ensure iron balance

EurekAlert, Public release date: 4-Aug-2010

MEASURING LEVELS OF FRATAXIN

Patent about methods and materials involved in measuring levels of a frataxin polypeptide present in a differents  biological samples.

MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH, OGLESBEE, Devin, MATERN, Dietrich, ISAYA, Grazia.

Adaptive robot training for the treatment of incoordination in Multiple Sclerosis

Journal of NeuroEngineering and Rehabilitation 2010, 7:37doi:10.1186/1743-0003-7-37

Elena Vergaro, Valentina Squeri, Giampaolo Brichetto, Maura Casadio, Pietro Morasso, Claudio Solaro and Vittorio Sanguineti.

OPEN ACCES

Abstract

Background
Cerebellar symptoms are extremely disabling and are common in Multiple Sclerosis (MS) patients. In this feasibility study, we developed and tested a robot therapy protocol, aimed at the rehabilitation of incoordination in MS subjects.

Methods
Eight subjects with clinically defined MS performed planar reaching movements while grasping the handle of a robotic manipulandum, which generated forces that either reduced (error-reducing, ER) or enhanced (error-enhancing, EE) the curvature of their movements, assessed at the beginning of each session. The protocol was designed to adapt to the individual subjects' impairments, as well as to improvements between sessions (if any). Each subject went through a total of eight training sessions. To compare the effect of the two variants of the training protocol (ER and EE), we used a cross-over design consisting into two blocks of sessions (four ER and four EE; 2 sessions/week), separated by a 2-week wash-out period. The order of application of ER and EE exercises was randomized across subjects. The primary outcome measure was the modification of the Nine Hole Peg Test (NHPT) score. Other clinical scales and movement kinematics were taken as secondary outcomes.

Results
Most subjects revealed a preserved ability to adapt to the robot-generated forces. No significant differences were observed in EE and ER training. However over sessions, subjects exhibited an average 24 % decrease in their NHPT score. The other clinical scales showed small improvements for at least some of the subjects. After training, movements became smoother, and their curvature decreased significantly over sessions.

Conclusions
The results point to an improved coordination over sessions, and suggest a potential benefit of a short-term, customized, and adaptive robot therapy for MS subjects.

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Development and pilot testing of HEXORR: Hand EXOskeleton Rehabilitation Robot

Journal of NeuroEngineering and Rehabilitation 2010, 7:36doi:10.1186/1743-0003-7-36

Christopher N Schabowsky, Sasha B Godfrey, Rahsaan J Holley and Peter S Lum.

OPEN ACCES

Abstract

Background
Following acute therapeutic interventions, the majority of stroke survivors are left with a poorly functioning hemiparetic hand. Rehabilitation robotics has shown promise in providing patients with intensive therapy leading to functional gains. Because of the hand's crucial role in performing activities of daily living, attention to hand therapy has recently increased.

Methods
This paper introduces a newly developed Hand Exoskeleton Rehabilitation Robot (HEXORR). This device has been designed to provide full range of motion (ROM) for all of the hand's digits. The thumb actuator allows for variable thumb plane of motion to incorporate different degrees of extension/flexion and abduction/adduction. Compensation algorithms have been developed to improve the exoskeleton's backdrivability by counteracting gravity, stiction and kinetic friction. We have also designed a force assistance mode that provides extension assistance based on each individual's needs. A pilot study was conducted on 9 unimpaired and 5 chronic stroke subjects to investigate the device's ability to allow physiologically accurate hand movements throughout the full ROM. The study also tested the efficacy of the force assistance mode with the goal of increasing stroke subjects' active ROM while still requiring active extension torque on the part of the subject.

Results
For 12 of the hand digits'15 joints in neurologically normal subjects, there were no significant ROM differences (P > 0.05) between active movements performed inside and outside of HEXORR. Interjoint coordination was examined in the 1st and 3rd digits, and no differences were found between inside and outside of the device (P > 0.05). Stroke subjects were capable of performing free hand movements inside of the exoskeleton and the force assistance mode was successful in increasing active ROM by 43 +/- 5% (P < 0.001) and 24 +/- 6% (P = 0.041) for the fingers and thumb, respectively. Conclusions Our pilot study shows that this device is capable of moving the hand's digits through nearly the entire ROM with physiologically accurate trajectories. Stroke subjects received the device intervention well and device impedance was minimized so that subjects could freely extend and flex their digits inside of HEXORR. Our active force-assisted condition was successful in increasing the subjects' ROM while promoting active participation.
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Neuroprotective properties of a novel, non-haematopoietic agonist of the erythropoietin receptor

Brain 2010 133(8):2281-2294; doi:10.1093/brain/awq101

Stanislava Pankratova1, Darya Kiryushko1, Katrin Sonn2, Vladislav Soroka1, Lene B. Køhler1, Mette Rathje1, Bing Gu1, Kamil Gotfryd1, Ole Clausen1, Alexander Zharkovsky2, Elisabeth Bock1 and Vladimir Berezin1

1 Protein Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, 2200 Copenhagen, Denmark 2 Department of Pharmacology, Centre of Excellence for Translational Medicine, University of Tartu, 51014 Tartu, Estonia

Keywords: Erythropoietin, central nervous system, neuroprotective agent, non-haematopoietic erythropoietin, Epotris, neurite outgrowth, blood–brain barrier, neurodegeneration, neurological disorders.

First causal treatment option for Friedreich's Ataxia via Erythropoietin (EPO)

Technology collaboration OFFER
Abstract
An Austrian university offers the first treatment option for Friedreich´s Ataxia (FRDA), an inherited neurodegenerative disease. It causally targets FRDA
using Erythropoietin (EPO) to increase the level of Frataxin, decreased levels of which are reportedly responsible for the development of FRDA. So far
no other effective treatment is available which is at an advanced development stage. Industrial partners for further developing & commercialising
EPO for the treatment of FRDA are sought.

Date de creation: 23 July 2010

Insulin signaling meets mitochondria in metabolism.

Trends Endocrinol Metab (2010), Published by Elsevier Ltd. DOI: 10.1016/j.tem.2010.06.005

Zhiyong Cheng, Yolanda Tseng and Morris F White
Howard Hughes Medical Institute, Division of Endocrinology, Children's Hospital Boston, Harvard Medical School, Boston MA, USA.

"chronic exposure to high ROS levels could alter mitochondrial function and thereby cause insulin resistance"

Klinik und Genetik der rezessiven Ataxien -[Clinical details and genetics of recessive ataxias.]

Nervenarzt. 2010 Jul 18. DOI: 10.1007/s00115-010-3079-4

Kühlke C, Kreuz F, Bürk K.

Institut für Humangenetik, Universität zu Lübeck.
[Article in German]

Iron-Sulfur (Fe-S) Cluster Assembly THE SufBCD COMPLEX IS A NEW TYPE OF Fe-S SCAFFOLD WITH A FLAVIN REDOX COFACTOR*

J. Biol. Chem. 2010 285: 23331-23341. First Published on May 11, 2010, doi:10.1074/jbc.M110.127449

Silke Wollers, Gunhild Layer, Ricardo Garcia-Serres, Luca Signor, Martin Clemancey, * Jean-Marc Latour, Marc Fontecave, and Sandrine Ollagnier de Choudens

ArmaGen® Re-engineers Erythropoietin For Brain Penetration

Medical News Today, Article Date: 17 Jul 2010

"EPO drug development for the brain is limited, because EPO does not cross the blood-brain barrier (BBB)"

"EPO-driven neuroprotection in human brain disorders is now possible with systemic administration of the HIRMAb-EPO fusion protein at doses that have minimal effects on erythropoiesis."

ArmaGen® Web

Oxidative stress, thiol redox signaling methods in epigenetics.

Methods Enzymol. 2010; 474: 213-44, doi:10.1016/S0076-6879(10)74013-1

Sundar IK, Caito S, Yao H, Rahman I

Keywords: Epigenetics, gene expression, posttranslational modifications, histones, histone acetylation, deacetylation, methylation, histone acetyltransferases (HATs), histone deacetylases (HDACs), reative oxygen species (ROS), signaling pathways, SIRT1.

Heterochromatin dysregulation in human diseases

J Appl Physiol 109: 232-242, 2010.
doi:10.1152/japplphysiol.00053.2010 

Matthias Hahn,^* Silvia Dambacher,^* and Gunnar Schotta
Munich Center for Integrated Protein Science (CiPS^M) and Adolf-Butenandt-Institute, Ludwig-Maximilians-University, Munich, Germany 

Keywords: epigenetics, heterochromatin, epigenetic therapy, FSHD, Friedreich's ataxia (FRDA), cancer

The Intermembrane Space of Mitochondria

Antioxidants & Redox Signaling.  doi:10.1089/ars.2009.3063.

Johannes M. Herrmann and Jan Riemer

Department of Cell Biology, University of Kaiserslautern, Kaiserslautern, Germany.

Review: Friedreich Ataxia and Erythropoietin

The Open Drug Discovery Journal, Volume 2, ISSN: 1877-3818
Review: Friedreich Ataxia and Erythropoietin, pp.18-24 (7)
Authors: Sylvia Boesch, Brigitte Sturm, Wolfgang Nachbauer, Sascha Hering, Hannes Steinkellner, Rainer Schneider, Werner Poewe, Barbara Scheiber-Mojdehkar
doi: 10.2174/1877381801002020018
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Iron-Overload Cardiomyopathy: Pathophysiology, Diagnosis, and Treatment

Journal of Cardiac Failure, Article in Press, Corrected Proof. Available online 3 July 2010.

Colm J. Murphy MD, FRCPC and Gavin Y. Oudit MD, PhD, FRCPC
Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada

Keywords: Cardiomyopathy; hemochromatosis; oxidative stress; anemia; cardiac MRI; echocardiography; primary (hereditary) hemochromatosis; secondary iron overload (hemosiderosis); iron toxicosis (iron poisoning); myocardial ischemia-reperfusion injury; cardiomyopathy associated with Friedreich ataxia; vascular dysfunction.

The Role of PGC-1alpha in the Pathogenesis of Neurodegenerative Disorders

Curr Drug Targets. 2010 Jul 1
Róna-Vörös K, Weydt P.
Department of Neurology, Ulm University, Ulm, Germany

Keywords: Mitochondrial dysfunction, neurodegeneration, Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), transcriptional co-activator PGC-1alpha.

Assessment of impairment or monitoring change in Friedreich ataxia

Movement Disorders, 10.1002/mds.23103
Letter to the Editor

Adam P. Vogel, MSc 1 2 *, Angela T. Morgan, PhD 3 4
1Centre for Neuroscience, University of Melbourne, Australia
2Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Melbourne, Australia
3Department of Paediatrics, University of Melbourne, Australia
4Healthy Development Theme, Murdoch Childrens Research Institute, Melbourne, Australia

"No abstract"

PGC-1α Regulates Expression of Myocardial Mitochondrial Antioxidants and Myocardial Oxidative Stress After Chronic Systolic Overload

Antioxidants & Redox Signaling. Ahead of print. doi:10.1089/ars.2009.2940.
Zhongbing Lu, Xin Xu, Xinli Hu, John Fassett, Guangshuo Zhu, Yi Tao, Jingxin Li, Yimin Huang, Ping Zhang, Baolu Zhao, Yingjie Chen.

Keywords: Mitochondria, reactive oxygen species (ROS, heart, Peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α), SOD2, and thioredoxin (Trx2), 3’-nitrotyrosine, 4-hydroxynonenal, TAC-induced myocardial oxidative stress, hypertrophy,dysfunction.