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.

Exercise Capacity and Idebenone Intervention in Children and Adolescents With Friedreich Ataxia

Archives of Physical Medicine and Rehabilitation, Vol=91, Issue 7, Pages 1044-1050 (July 2010)
( Presented in part to the American College of Sports Medicine, Seattle, WA, May 28, 2009.)

Drinkard BE, Keyser RE, Paul SM, Arena R, Plehn JF, Yanovski JA, Di Prospero NA. 

Keywords: Friedreich's Ataxia (FA), idebenone, randomized double-blind, placebo-controlled, oxidative stress, peak oxygen consumption per unit time (peak VO2), peak work rate (WR), Echocardiography, neurologic assessments, exercise.

Innovative gait robot for the repetitive practice of floor walking and stair climbing up and down in stroke patients

Journal of NeuroEngineering and Rehabilitation 2010, doi:10.1186/1743-0003-7-30

Stefan Hesse, Andreas Waldner; and Christopher Tomelleri

Published:28;June;2010

OPEN ACCES

Background

Stair climbing up and down is an essential part of everyday's mobility. To enable wheelchair-dependent patients the repetitive practice of this task, a novel gait robot, G-EO-Systems (EO, Lat: I walk), based on the end-effector principle, has been designed. The trajectories of the foot plates are freely programmable enabling not only the practice of simulated floor walking but also stair climbing up and down. The article intended to compare lower limb muscle activation patterns of hemiparetic subjects during real floor walking and stairs climbing up, and during the corresponding simulated conditions on the machine, and secondly to demonstrate gait improvement on single case after training on the machine.

Methods

The muscle activation pattern of seven lower limb muscles of six hemiparetic patients during free and simulated walking on the floor and stair climbing was measured via dynamic electromyography. A non-ambulatory, sub-acute stroke patient additionally trained on the G-EO-Systems every workday for five weeks.

Results

The muscle activation patterns were comparable during the real and simulated conditions, both on the floor and during stair climbing up. Minor differences, concerning the real and simulated floor walking conditions, were a delayed (prolonged) onset (duration) of the thigh muscle activation on the machine across all subjects. Concerning stair climbing conditions, the shank muscle activation was more phasic and timely correct in selected patients on the device. The severely affected subject regained walking and stair climbing ability.

Conclusions

The G-EO-Systems is an interesting new option in gait rehabilitation after stroke. The lower limb muscle activation patterns were comparable, a training thus feasible, and the positive case report warrants further clinical studies.

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Gene Therapy a Step Closer to Mass Production

ScienceDaily (June 24, 2010) — EUREKA project E! 3371 Gene Transfer Agents has made great advances in the development of novel non-viral carriers able to introduce genetic material into the target cells. These new agents, derivatives of cationic amphiphilic 1,4-dihydropyridine (1,4-DHP), avoid the problems of the recipient's immune system reacting against a viral carrier.

Transposon Tn7 Preferentially Inserts into GAA•TTC Triplet Repeats under Conditions Conducive to Y•R•Y Triplex Formation

Mancuso M, Sammarco MC, Grabczyk E, 2010 Transposon Tn7 Preferentially Inserts into GAA•TTC Triplet Repeats under Conditions Conducive to Y•R•Y Triplex Formation. PLoS ONE 5(6): e11121. doi:10.1371/journal.pone.0011121

OPEN ACCES

Abstract

BACKGROUND: Expansion of an unstable GAA*TTC repeat in the first intron of the FXN gene causes Friedreich ataxia by reducing frataxin expression. Structure formation by the repeat has been implicated in both frataxin repression and GAA*TTC instability. The GAA*TTC sequence is capable of adopting multiple non-B DNA structures including Y*R*Y and R*R*Y triplexes. Lower pH promotes the formation of Y*R*Y triplexes by GAA*TTC. Here we used the bacterial transposon Tn7 as an in vitro tool to probe whether GAA*TTC repeats can attract a well-characterized recombinase. METHODOLOGY/PRINCIPAL FINDINGS: Tn7 showed a pH-dependent preference for insertion into uninterrupted regions of a Friedreich ataxia patient-derived repeat, inserting 48, 39 and 14 percent of the time at pH 7, pH 8 and pH 9, respectively. Moreover, Tn7 also showed orientation and region specific insertion within the repeat at pH 7 and pH 8, but not at pH 9. In contrast, transposon Tn5 showed no strong preference for or against the repeat during in vitro transposition at any pH tested. Y*R*Y triplex formation was reduced in predictable ways by transposon interruption of the GAA*TTC repeat. However, transposon interruptions in the GAA*TTC repeats did not increase the in vitro transcription efficiency of the templates. CONCLUSIONS/SIGNIFICANCE: We have demonstrated that transposon Tn7 will recognize structures that form spontaneously in GAA*TTC repeats and insert in a specific orientation within the repeat. The conditions used for in vitro transposition span the physiologically relevant range suggesting that long GAA*TTC repeats can form triplex structures in vivo, attracting enzymes involved in DNA repair, recombination and chromatin modification.

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Researchers create new 'smart' nanocapsule delivery system for use in protein therapy

UCLA Newsroom, Wileen Wong Kromhout December 17, 2009


Protein therapy — the delivery of healthy proteins directly into human cells to replace malfunctioning proteins — is considered one of the most direct and safe approaches for treating diseases. But its effectiveness has been limited by low delivery efficiency and the poor stability of proteins, which are frequently broken down and digested by cells' protease enzymes before they reach their intended target.     read more