Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease, is a neurodegenerative disorder of motor neurons, leading to paralysis and eventual respiratory failure. The disease is invariably fatal and there is neither a cure nor even an effective treatment. A team of researchers led by Eric Olson at the University of Texas Southwestern Medical Center has identified miR-206 as a modifier of ALS pathogenesis and has defined a role for a microRNA (miR-206) in reinnervating the neuromuscular junction after injury and improving survival in a mouse model of the disease. miRNAs are small non-coding RNA molecules which down-regulate gene expression and dysfunction of miRNAs has been associated with a number of diseases. The authors searched for miRNAs involved in amyotrophic lateral sclerosis (ALS) by comparing expression of 320 miRNAs in the lower limb muscles of normal mice and a common model for the disease, animals expressing human superoxide dismutase 1 (SOD1) with a G93A mutation. They found that miR-206 was upregulated to more than three times its normal expression levels with the onset of disease. Following denervation, expression of miR-206 increased by more than 10-fold in healthy mice, suggesting it may be part of a common response to nerve injury. They then generated and characterized targeted mutants of the miRNA-206 gene, and crossed them to the ALS mice. They found that loss of miRNA-206 had little effect on development of muscle or neuromuscular synapses, but speeded disease progression by slowing the ability of axons to form new synapses on denervated muscle fibers. Furthermore, they showed that miRNA-206 normally coordinates the muscle’s response to denervation, in part by increasing the efficacy of signals that the muscle sends back to the nerve. The results suggest that factors expressed and secreted from skeletal muscle have a positive role in maintaining the signaling between motor neuron and skeletal muscle during injury and disease. One of the hallmarks of ALS and other similarly degenerative muscle diseases is the inability of the neuromuscular synapse to transmit the impulse that leads to muscle contraction. The data from this study show that miR-206 plays a central regulatory role in this process, a potentially promising target for therapeutic intervention in ALS and other neuromuscular diseases.

Interim results from AVI BioPharma’s current clinical trial of the exon-skipping compound AVI-4658 in boys with Duchenne muscular dystrophy (DMD) show that when the compound is delivered systemically, rather than simply injected into a foot muscle as in a previous trial, it appears safe and leads to production of the missing muscle protein dystrophin. Exon skipping is among the most promising strategies for treatment of DMD, and the AVI4658 results bode well for this compound and others of its type. Restoration of dystrophin, a key component of muscle, theoretically could restore muscle function or halt its deterioration in DMD. The newly announced trial results reflect an ongoing phase 1b/2 clinical trial of AVI4658 for the systemic treatment of DMD. The interim results are for participants in the first four of six dosage groups who have completed 12 weeks of treatment with different doses of AVI4658 (0.5, 1, 2 or 4 mg/kg) and have undergone muscle biopsies. The post-treatment muscle biopsy samples revealed that the three trial participants who received 2 and 4 mg/kg of AVI4658 showed mRNA for dystrophin that reflect skipping of exon 51, accompanied by production of dystrophin protein. One trial participant, in the 2-milligram dosage group, showed significant production of dystrophin with treatment, which encourages the investigators to expect even greater levels of dystrophin expression following treatment with the higher doses of 10.0 mg/kg and 20.0 mg/kg of AVI-4658. No dystrophin was seen in the biopsy samples from patients who received 0.5 or 1 mg/kg of AVI4658. Nineteen patients are now enrolled in this trial, with some receiving dosages of 10 and 20 mg/kg of intravenous AVI4658. Presently, the strategy only applies to people who can benefit from skipping exon 51. However, if this approach proves successful, other exon-skipping compounds can be developed targeting other dystrophin mutations.

28 February 2010: Early registration deadline
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in conjunction with the European Meeting on Psychosocial Aspects of Genetics
Abstract submission is open
Registration is open
Deadline for abstracts submission:  February 19, 2010
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18 January 2010: Abstract submission deadline

28 February 2010: Early registration deadline

Organized by Genopole® together with Genethon, partner of the ADNA program (Advanced Diagnostics for New Therapeutic Approaches) program coordinated by Mérieux Alliance, the conference gathered in Paris on December 10th, 2009, various actors implicated in the discovery, follow up and validation of new biomarkers in the development of a personalized medicine.
Conference first session was dedicated to monogenic rare diseases. Thomas Voit, Scientific and Medical Director of the Institute of Myology presented several types of biomarkers related to Duchenne Muscular Dystrophy (DMD). Two points were highlighted during his talk : the importance of miRNA which expression patterns vary according to the neuromuscular diseases, and the choice of the methodology used for identification of the biomarkers and their functions. Brenda Wong, Associate Professor of Pediatrics and Neurology at the Children’s Hospital Medical Center de Cincinnati (USA) presented her team's results on the use of biomarkers in diagnostic as well as pathophysiological and therapeutic follow up in DMD.
Besides, the talk of Marc Peschanski, Scientific Director of ISTEM laboratory was related to biomarkers use in screening of potential therapeutic compounds. The technique developed by ISTEM's researchers allows to identify biomarkers in a population of embryonic stem cells carrying DM1 mutation combined with Steinert disease.

Talks from all sessions will soon be available on Génopole® website.

This book provides a detailed scientific treatment of the emerging disciplines of personal genomics and personalized medicine. It also includes a comprehensive treatment of both the promises and challenges of personal genomics and medicine from technological, societal and medical perspectives. It offers a wide-ranging review of the state of the art across all aspects of a highly multi-disciplinary subject. This book will be immensely useful for practicing health professionals and researchers, as well as senior undergraduates and graduate students in biomedical sciences.
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This manual is designed to serve as a practical guide to primary human cell culture, which is integral in both academic and industrial biotechnology research. This improved second edition also includes a new section on stem cells and additional material on transfection. It should serve as a foundation for individual researchers to experiment, explore, and establish niche protocols for their specific needs. With its compact physical format that makes it portable and flexible for usage in a laboratory setting, the manual will be a useful guide for all beginners in primary human cell culture work.
> A Manual for Primary Human Cell Culture (2nd Edition)

The Senator Paul D. Wellstone Muscular Dystrophy Research Cooperative Research Center at the University of North Carolina at Chapel Hill is offering 1-year or 2-year training opportunities for both pre-doctoral and post-doctoral fellows in research targeted at gene therapy for muscular dystrophy.

 

Fellowship positions are open to pre-doctoral students with a bachelor’s degree or post-doctoral students with an earned doctorate (Ph.D., M.D., D.V.M., etc) who are interested in basic, clinical or translational research related to any of the diverse disciplines that collaborate to develop and implement gene therapy for human muscular dystrophies. These include engineering and testing of viral vectors (Dr. Jude Samulski), design and testing of gene therapy in animal models (Drs. Xiao Xiao and Joe Kornegay), muscle imaging (Dr. Weili Lin), clinical evaluation (Drs. James F. Howard, Jr and Spencer Weig) and testing of delivery systems for human limbs (Dr. William Powers).

 

The bimonthly Newsletter of the Institute of Myology keeps you up to date with developments in myology research, and presents a summary of the latest scientific, medical, political and associative news concerning neuromuscular diseases.

You can access our Newsletter by connecting directly to the Institute of Myology website, or by subscribing.

 

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