The AFM has launched its Call for Proposals with two review sessions. The deadlines are  October 2, 2009 (first session) - notification expected mid-February 2010 and March 5, 2010 (second session) - notification expected mid-July 2010. This international call for proposals is centred around three axes that will i) lead to a better fundamental understanding of the neuromuscular system ii) encourage the development of therapies for neuromuscular diseases and rare genetic diseases and III) improve care and quality of life of patients with neuromuscular diseases.
> Please visit the AFM website for more information on their calls for proposals and fellowships

The 8th French-Japanese Workshop on Muscular Dystrophies, “From pathophysiology to biotherapies”, was held on July 3–4, 2009, at the Institute of Myology. Thirty speakers followed one after the other, talking on basic biology, molecular genetic, physiopathology and biotherapies. Thomas Voit kicked off this very dense two-day workshop which began with David Sassoon's talk whereas Shin'ichi Takeda closed the the last session.

 

Prosensa, the Dutch based biopharmaceutical company focusing on RNA modulating therapeutics, announces the successful completion of a feasibility enquiry using the TREAT-NMD Global Database for DMD and the TREAT-NMD Care and Trial Sites Registry (CTSR) for the planning of the phase II/III study for its lead compound PRO-051. This will be the first of many collaborative ventures for TREAT-NMD as they work together toward planning new clinical trials for neuromuscular diseases.
> Read the Press Release

Muscular dystrophy, a group of inherited diseases characterized by progressive skeletal muscle weakness, can be caused by mutations in any one of a number of genes. In this study, Japanese researchers identify a new gene mutation linked to muscular dystrophy. The finding came from genetic analyses of five people with muscular dystrophy and lipodystrophy. Their muscles were deficient in caveolin-3 protein, but they did not have mutations in the caveolin-3 gene, which have been linked to muscular dystrophy. The researchers found a mutation in the PTRF gene, which makes a protein believed to influence caveolin protein stabilization. Further investigation showed that the mutated forms of the PTRF gene produced mutant PTRF proteins that could not localize correctly or associate with caveolin proteins. Based on their findings, the researchers concluded that the muscular dystrophy in the five people they studied was probably the result of caveolin deficiencies secondary to PTRF gene mutations.
Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy

Myotonic dystrophy is the most common form of muscular dystrophy in adults, with a prevalence of 1 in 8,000. It is a multisystem disorder characterized by progressive muscle wasting and weakness, particularly in the lower legs, hands, neck, and face. It is well established that RNA is a central player in myotonic dystrophy. Triplet repeat expansion of dystrophia myotonica protein kinase (DMPK) causes the nuclear retention of mutant messenger RNA (mRNA). Currently there is no cure for myotonic dystrophy and there are no treatments. In this paper, Dr. Charles Thornton and colleagues at the University of Rochester Medical Center describe a novel way to block the genetic flaw key in the development of myotonic dystrophy.  The researchers used a morpholino antisense oligonucleotide, CAG25 to break up deposits of toxic RNA and re-establish the cellular activity that is disrupted by the disease. It is believed that potentially all of the symptoms of myotonic dystrophy flow from this single genetic flaw, therefore neutralizing it could potentially restore muscle function in people with the disease. When injected into the muscle cells of mice with myotonic dystrophy, CAG25 found its way to the cell nucleus, broke up the deposits of toxic RNA, freed the captive muscleblind proteins, and ultimately improved the molecular structure function of the muscle cells. The researchers specifically observed a restoration of proper electrical control in the cells, which is a convenient way to monitor the condition. However, major hurdles must be overcome before this compound can be tested in humans. Specifically, a better delivery system must be developed so that this or a similar compound attains its target in the body, and the potential side effects must be carefully analyzed. This study demonstrates the potential to reverse established symptoms of the disease after they have developed, as opposed to simply preventing them from getting worse. This study establishes a proof of concept that could be followed to develop a successful treatment for myotonic dystrophy. This is important because it impacts the molecular underpinning of myotonic dystrophy and is a major step forward in being able to develop treatments for it.

Organised by the EuroMyasthenia Network
New extended abstract submission deadline : Friday, September 18, 2009
> More information

Identification of two new genes responsible for a congenital myasthenic syndrome and Emery-Dreifuss muscular dystrophy

 

Research teams at the Institut de Myologie (Myology Institute) in Paris have identified two new genes responsible for neuromuscular diseases: a congenital myasthenic syndrome and Emery-Dreifuss muscular dystrophy. A crucial milestone in terms of understanding these diseases and developing treatment strategies, in the immediate term, these discoveries will make it possible to more accurately diagnose diseases and offer genetic counselling to the families concerned.

Neuromuscular junctions (NMJ) form in three steps that include specific nerve-muscle recognition, synaptic differentiation, and maturation of the synapse. In some congenital myasthenic syndromes or autoimmune diseases, one of these steps is perturbed during development and leads to functional defects at the synaptic contact with more or less severe muscle weakness. These defects also appear postnatally with very high incidence following traumatic nerve injury or nerve section during surgery. To stimulate formation or regeneration of the synapse, one needs to understand the molecular and cellular bases for the establishment of such a specialized contact where the pre and postsynaptic cells become precisely apposed and differentiate. To date, most of the molecular players that have been unraveled at the NMJ are involved in synapse differentiation and maturation. However, the early step corresponding to nerve-muscle recognition is still «a black box ». The aim of this proposal is to investigate the signals that come from the muscle to instruct the nerve terminal of its final attachment site on the muscle.
This work will be done in collaboration between Claire Legay’s lab and Pascal Maire’s lab.
The position is for 2 years starting January 2010.
For more information and to apply for this position, please contact

Claire Legay: Claire.legay(a)univ-paris5.fr or 
Pascal Maire: pascal.maire(a)inserm.fr

Two post-doctoral positions are available in the laboratory of Dr. Natalia Shirokova in the Department of Pharmacology and Physiology, University of Medicine and Dentistry, New Jersey Medical School. Their research is focused on mitochondrial and redox regulation of calcium signaling in skeletal and cardiac muscle under physiological and pathophysiological conditions (e.g. in muscular dystrophy). They use electrophysiological methods in combination with video-rate, single and two photon confocal imaging, and UV-flash photolysis of caged compounds. Research experience in one of the techniques listed above is required. A strong background in muscle physiology is highly desirable. For more information and a list of their publications, please visit http://njms.umdnj.edu/departments/pharmacology/faculty/shirokova/.
Salary and fringe benefits will be highly compatible and commensurate with experience. Application including a cover letter, CV and the names of three references should be e-mailed to nshiroko(a)umdnj.edu.

This is the first full-length intellectual biography of Francis Crick, a greatly admired and influential scientist who co-discovered the structure of DNA and then followed up this discovery with important contributions that shaped the foundations of molecular biology. He later worked in the field of neuroscience, studying vision and the biological basis of consciousness. This book is an in-depth exploration of Crick's passion for the discovery and understanding of the molecules that orchestrate the essential processes of life.

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