Marie-Agnes Metgès is a lecturer and hospital practitioner at the University Hospital of Brest. At the hospital, she is responsible for a lung function testing unit, which caters mainly to children. Moreover, her basic research focuses on the adaptation of the neuromuscular system to environmental constraints. She currently works at the Institute of Myology in Yves Fromes group in the laboratory of experimental physiology.  

 

What is your research thematic at the Institute?
We are seeking to understand the mechanisms of the nervous system adaptation to the progressive muscular weakness and impairment: what is the new equilibrium between the muscle and its nervous control?  In this context, we are studying the limb girdle muscular dystrophy observed in the CHF147 hamster, a spontaneous animal model of delta-sarcoglycan deficiency.

Duchenne muscular dystrophy (DMD) is the most common and lethal genetic muscle disorder currently lacking a curative treatment. Palliative treatment for DMD can prolong the lifespan of patients, but the prognosis is limited, and a progressive reduction in quality of life and early death in adulthood cannot be prevented using currently available treatment regimens. The best hopes for a cure lies with cellular and gene therapy approaches that target the underlying genetic defect. The helper-dependent adenovirus (HDAdv) is the only viral vector that can accommodate the large size of the full-length dystrophin complementary DNA. This study carried out by a team of Japanese scientists aimed to investigate whether gene transfer by HDAdv to multiple proximal skeletal muscles of utrophin/dystrophin double knockout (dko) mice was effective as a therapy for muscular dystrophy. Examination of the muscle pathology 8 weeks post-injection clearly showed that dystrophin was expressed beneath the sarcolemmal in wild-type and injected dko mice. The dystrophin associated proteins, β-dystroglycan, and α-sarcoglycan as well as neuronal nitric oxide (nNOS) were also expressed in the dystrophin positive fibres of both groups, whereas myc-tag (confirms that the dystrophin was derived from the transferred gene) was expressed only in the injected dko mice.  There was a significant reduction in the number of centrally nucleated fibres in the injected dko mice compared with uninjected dko mice. There were much fewer immune cells in the injected dko muscles than in the uninjected dko muscles. Furthermore, vector-injected dko mice showed an increase in body weight, improved motor performance and lived longer. These results may have a potential use in the establishment of an effective therapy for muscular dystrophy.

Researchers at Cold Spring Harbor Laboratory (CSHL) and Isis Pharmaceuticals have devised a potential approach to treat the neuromuscular disease spinal muscular atrophy (SMA) caused by a deficiency in the survival of motor neuron protein (SMN) caused by a single gene mutation. SMA is a neurodegenerative disease of the motor neurons and results in progressive muscle weakness. It is also the leading hereditary cause of infant mortality. CSHL professor Dr. Adrian Krainer and his team have devised a method to stimulate cells to replenish the SMN protein by activating an existing, slightly modified copy of the mutant gene, survival of motor neuron 1, centromeric (SMN1). The researchers injected antisense oligonucleotides (ASO) into mice that had an added, human version of the SMN2 gene. As expected, the gene produced significantly more SMN RNA, including the section that is usually omitted, in tissues where the ASOs accumulate. These results highlight the therapeutic potential of some of these ASOs in the context of SMA. However, before this approach can be applied to human patients, several additional issues must be addressed-such as whether the ASOs really benefit growing animals with SMA and how and when they should be administered to affect the nervous system.

Dutch researchers from University Medical Centre Utrecht and the Hubrecht Institute have made a breakthrough in stem cell research by successfully growing stem cells from adult human hearts into new heart muscle cells. For a long time, researchers thought that the adult heart contained no stem cells. However, recent studies have revealed the existence of a small pool of potential stem cells in the adult heart. In this latest study, principal investigator Professor Doevendans and his team succeeded in isolating some of these stem cells from the material left over from open-heart surgery. Until now, scientists have relied on human embryonic stem cells to create heart stem cells. However, this method is not very productive, as many of the cells do not develop into muscle cells. Furthermore, isolating stem cells from embryos remains a controversial issue. The researchers cultured these cells in the laboratory and allowed them to develop. Almost all the cells developed spontaneously into mature heart muscle cells that contract rhythmically and respond to both electrical activity and adrenaline. These cultured heart muscle cells will enable scientists to study heart defects and test new medicines, and could one day be used to repair heart tissue which has been damaged during a heart attack. The findings are published in the latest issue of the journal Stem Cell Research.

• Myostatin shows promise for Muscular Dystrophy - Read
• Hepatitis C drug may offer potential treatment strategy for Muscular Dystrophy - Read
• Standards of care for Duchenne muscular dystrophy - Brief TREAT-NMD recommendations - Read
• Homozygous R471C LMNA mutation results in a new severe phenotype - Read
• Mutations in the dysferlin gene can cause amyloidosis - Read
• NORD Announces 2008 Funding Opportunities - Read
• Special report on DMD-BMD research - Read
• NIH to Host Research Symposium on Clinical Applications of Stem Cell Therapies - Read
• United Parent Projects MD (UPPMD) launch an interactive website for the Duchenne Community - Read
• Development of novel polymer-oligonucleotide drugs for treatment of Duchenne Muscular Dystrophy - Read
• McArdle disease is associated with systemic low-grade inflammation - Read
• PTC Therapeutics Initiates Phase IIb Muscular Dystrophy Trial - Read

Every year the Institute of Myology in Paris offers a high level 10-day teaching program in English covering various topics from basic myology to the different aspects of the ever progressing knowledge of muscle diseases. The course is comprised of a series of lectures, seminars and interactive workshops.

Registrations are closed for this edition, yet you can register for next year.

> For more information

MYORES - the European Muscle Development Network of Excellence – is organising a workshop to introduce graduate students and post-docs to Bio-informatics methods for developmental muscle research. This workshop will focus on the basics of sequence analysis/comparison, the use of databases and the methods for gene transcription analysis.
Registration deadline: June 27th, 2008

 

The chosen topics for this year’s congress are:
1. New insights into the pathogenesis of facioscapulohumeral muscular dystrophy, myotonic dystrophy and other dominanat muscular dystrophies.
2. Advances in the understanding and treatment of myasthenic disorders.
3. Therapeutic advances in neuromuscular disorders.

Mark your calendars for the 2008 EPPOSI workshop, taking place at the National Assembly in Paris. The theme of the workshop is Orphan drugs: partnering along the chain and across the borders - Sharing strategies and tools for access to diagnosis and treatment.

11/04/2007 - Result of Téléthon 2007 : 102.3 million Euros for the turning point to treatments to succeed - Thank you, everyone!
€ 102 315 233 : this is the final result of Téléthon 2007, organised on 7 and 8 December by the Association Française contre les Myopathies (AFM) and France Télévisions, with the support of the regional stations of the Radio France Group. Although after thirty hours of programming the counter of donations promised stood at € 96 228 136, the final figure came to over 6% more than that.
> Access the complete press release

Molecular and Cell Biology of Muscular Dystrophy gives a series of accounts of various aspects of the remarkable breakthrough which has been achieved in our understanding of the Duchenne/Becker muscular dystrophies and of the consequences and ramifications of this breakthrough. Subject areas covered include: Molecular human genetics and the Duchenne/Becker muscular dystrophy gene; Molecular genetics and genetic counselling for Duchenne/Becker muscular dystrophy; Inheritance and pathogenicity of myotonic dystrophy; Dystrophin-associated glycoproteins: their possible roles in the pathogenesis of muscular dystrophy; Molecular and cell biology of skeletal muscle regeneration; Human dystrophin gene transfer: genetic correction of dystrophin deficiency; Myoblast transplantation in inherited myopathies.

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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