This is the 3rd international Myology congress organized by the AFM since 2000. Thomas Voit will chair the congress and Ketty Schwartz will be the honorary president.

 

As specified by Thomas Voit: “It is necessary for us to exchange, compare and learn from others how to progress, such are the objectives of this congress. And this will all be done in a collaborative frame of mind”. This unique gathering of international myology experts is of great importance for the community of ‘myologists’ because it encourages exchanges necessary to overcome the obstacles for the development of innovative therapeutics and the establishment of clinical trials in man.

 

Among the developments for this Myology 2008 edition is the advocacy to approach both themes of the conference each day -fundamental and therapeutic- across transverse subjects or  pathology. Another novelty is that the last day of the congress will also be the 1st day of the 5th international congress of rehabilitation in neuromuscular diseases (May 30 to June 1, 2008).

 

We will keep you informed of the programme and all other formalities for these two events: inscription and submission of abstracts will take place in September.

Myoblast transfer therapy (MTT) is one therapeutic strategy for Duchenne Muscular Dystrophy that has been pursued for many years. In this therapy, myoblasts expressing normal dystrophin are transplanted in order to contribute their functional dystrophin to the multinucleated myofibres with which their differentiating progeny eventually fuse. Progress in this area has been limited by biological problems such as cell death and failure to proliferate and migrate. An additional obstacle is the lack of an immortal normal human myoblast cell line, so that almost all of our information is based on rodent myoblasts which may differ in important ways.

 

The aim of this study was to create a reliable model of immortalized myoblasts that display all signs of normal differentiation. Such a cell line has never been isolated, and would represent a powerful tool to study the parameters involved in the success or failure of MTT, thus allowing an optimization of this therapeutic approach using human cells. Moreover, reliable in vitro models of various neuromuscular diseases could be created, which would represent crucial tools (i) to analyse the molecular pathways involved in the process of the diseases and (ii) to develop therapeutic strategies, e.g. high throughput analyses of pharmacological molecules to correct these perturbed molecular pathways. In order to create these models, optimised culture conditions and the expression of human telomerase reverse transcriptase (hTERT) in combination with cyclin-dependent kinase 4 (cdk4) have been employed, avoiding the use of viral oncoproteins. This report describes the production and characterization of a human myogenic cell line, LHCNM2, that has overcome replicative aging due to the expression of telomerase and cdk4. This immortal human myoblast cell line functions as well as the best human primary cultures in xenotransplant experiments in immunocompromized mice under conditions of regeneration following muscle damage.

 

This will prove to be a valuable reagent that can be shared between laboratories, and this approach can be applied to the production of immortal lines from a variety of different human myopathies. The most important implications of immortalizing human myoblasts that retain a normal karyotype and differentiate normally lies in the creation of a normal human myoblast for the development of a universal donor engineered to function therapeutically in human patients.

This was work was partly supported by the AFM.

Walker Warburg syndrome (WWS) is an autosomal recessive condition characterized by congenital muscular dystrophy, structural brain defects and eye malformations. Typical brain abnormalities are hydrocephalus, lissencephaly, agenesis of the corpus callosum, fusion of the hemispheres, cerebellar hypoplasia and neuronal overmigration, which causes a cobblestone cortex. Ocular abnormalities include cataract, microphthalmia, buphthalmos, and Peters' anomaly. WWS patients show defective O-glycosylation of alpha-dystroglycan (alpha-DG). This protein plays a key role in bridging the cytoskeleton of muscle and central nervous system cells with extracellular matrix proteins, important for muscle integrity and neuronal migration. Mutations in the genes FCMD, FKRP, POMT1 and POMT2, affect the glycosylation of alpha-dystroglycan and result in phenotypic variability ranging from WWS to limb-girdle muscular dystrophy. Mutations in the glycosyltransferase gene LARGE, also result in the hypoglycosylation of alpha-dystroglycan. The authors of this paper sought to investigate whether allelic variability also occurs for the LARGE gene. To this end, intragenic and LARGE flanking genetic markers were selected to test for homozygosity in 30 WWS patients from consanguineous parents. They found a homozygous 63-kb intragenic deletion in LARGE in one patient with WWS, indicating that LARGE is responsible for a small percentage of WWS patients. This data demonstrate that the LARGE gene mutation can lead to a wide clinical spectrum, similar to the previously described genes. The authors have uncovered a fifth causative gene for WWS.

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant, late-onset, progressive disease that generally presents in the fifth or sixth decade with dysphagia, ptosis and proximal limb weakness. OPMD is caused by the abnormal expansion of a (GCG)n trinucleotide repeat in the coding region of the poly-(A) binding protein nuclear 1 (PABPN1) gene, an abundant nuclear protein. Polyadenylation and transport of mRNA are the principal functions of PABPN1, but the protein also appears to control gene expression. The mechanism by which the expansion results in a pathological phenotype and the selective engagement of specific types of skeletal muscle in OPMD is still not understood. Furthermore, mitochondrial abnormalities have been previously reported in the muscles of OPMD patients but their importance has not been elucidated.

 

In this study led by Dr. R. Lane from the Imperial College London, monozygotic twins with identical PABP2 expansions but noticeably different clinical severity of OPMD were studied to determine whether mitochondrial DNA abnormalities were responsible for the observed changes. Histological, electron microscopy, clinical and genetic examinations were performed. Ragged red fibres were present and cytochrome oxidase (COX) staining displayed partial and complete loss of activity in some fibres. These findings were more remarkable in one of the twins. However, similar abnormal mitochondrial accumulations with extensive peripheral mitochondrial aggregates were seen in both twins. On clinical examination, a more pronounced muscle wasting in the arms and torso and more severe facial and lower limb wasting in the legs was observed in one of the twins and not the other. Molecular genetic results showed identical heterozygous expansions of the PABP2 gene in the twins but different multiple mtDNA deletions.

 

This is the first study to demonstrate, using Southern blotting, a possible relationship between the presence of mitochondrial myopathy and the existence of mtDNA deletions in OPMD patients.

At the initiative of professors R. Whalen and S. Takeda, a first conference organized in 1995 concerning gene therapy of neuromuscular diseases aimed to promote collaborations between France and Japan. Since then, researchers from the two countries gather every two years, alternatively between France and Japan, and discuss myology themes and therapeutic possibilities for neuromuscular diseases.

 

Chaired jointly by professors H. Sugita and M. Fardeau, the 7th edition of the Franco- Japanese conference gathered 70 researchers and doctors involved in the latest developments of myology and molecular therapies of muscular dystrophies.

 

On the 22nd May 2007, the Myology Institute held its first workshop devoted to facioscapulohumeral myopathy (FSHD). Twelve research scientists from six countries gathered to provide an update on the genetic, physiopathological and therapeutic research advances in FSHD. Here we present a brief report of this workshop.

 

FSHD is a muscular dystrophy characterized by significant atrophy of the facial (Facio), scapular (Scapulo) and upper arm (Humeral) muscles. It is an autosomal dominant genetic disease resulting from integral deletions of the subtelomeric repeat D4Z4 on chromosome 4q (4q35). It is the third most common myopathy after Duchenne and myotonic dystrophy, with a prevalence of 1:14000.

 

 

The 6th international myotonic dystrophy meeting will be organized by Dr. Giovanni Meola.
A broad range of topics will be covered, ranging from DNA instability to future advances for treatment. It is hoped that the collegial atmosphere will encourage stimulating exchanges between researchers, physicians and other care providers (neurologists, internists, paediatricians, occupational and physical therapists, geneticists and counsellors, ophthalmologists, oral surgeons, anaesthesiologists, gynaecologists, cardiac and pulmonary medicine specialists, gastroenterologists and endocrinologists) and patients.
Between 200-300 investigators, physicians and patients are expected to attend.

 

> Preliminary programme

> For more information

This school will be divided in two parts: The first part will take place from the 16th to 19th September in Evry, where plenary lectures will be accompanied by short communications mainly by young researchers, followed by a practical course, from the 19th to 22nd September at Maison-Alfort. The practical course will be centred around gene transfer techniques into muscle and skin.

The workshop aims to introduce graduate students and post-docs to molecular muscle research and to the model organisms used to study myogenesis and muscle regeneration.
A total of 50 students/post-docs can participate in the workshop, 20 of whom must be involved in the Myores network. Students and post-docs are expected to present a poster on the first day of the workshop.

Deadline for registration is the 1 August 2007.

Over 800 participants from child neurology and related fields are expected to attend the congress to exchange their ideas and findings in research, diagnosis and treatment, finding an excellent opportunity to assess the state of knowledge in the field and present an update.

 

The symposium will be in the traditional WMS format with 3 selected topics: 1. New developments in metabolic disorders of muscle (including disorders of glycogen, lipid metabolism and mitochondria), 2. Update on congenital muscular dystrophies and congenital myopathies, 3. What’s new in therapy of neuromuscular disorders?

 

EUROGLYCANET, in collaboration with the Orphan Europe Academy and the Faculty of Pharmacy, is very pleased to propose the 3rd focus course on the field of inborn errors of glycosylation.
The course programme will be divided into state-of-the-art lectures and practical sessions from basic science to the clinical, biochemical and genetic aspects of CDG. It will be the occasion to discuss the recent identification of defects that affect trafficking and function of the glycosylation machinery. Furthermore it will be an excellent introduction to the Third International Meeting on CDG and related disorders, which will be held following this course, also in Paris.

 

> For more information

The biennial European Conference on Rare Diseases organised by Eurordis and its partners,
under the patronage of the Portuguese Ministry of Health, in the context of the Portuguese EU Council Presidency and supported by the European Commission.

 

> For more information: email Kasia Peala kpeala@eurordis.org

 

 

 

 

 

Stem cells represent a therapeutic hope for numerous pathologies, and this is particularly true for cases of heart failure. With the use of stem cells, the damaged tissue of the heart could be regenerated. Inserm’s AVENIR team led by Michel Pucéat (Inserm Unit 861: I-stem ) is one of the first French teams to have been authorised to work on human embryonic stem cells. In collaboration with Philippe Menasché, cardiac surgeon at the Georges Pompidou European Hospital (AP-HP, Paris 5 University) and director of the “Cell therapy in cardiovascular pathology” Inserm Unit 633, Michel Pucéat’s team has just demonstrated for the first time that human embryonic stem cells can differentiate themselves into cardiac cells in the failing hearts of rats.
 
This work was carried out at the I-Stem laboratory, led by Marc Peschanski. It is the result of a partnership between the Association Française contre les Myopathies (AFM), Inserm, Génopole and the University of Evry, and is published by the review Stem Cells.

This is the first book that provides a comprehensive review of the entire area of artificial cells, otherwise known as blood substitutes, bioencapsulation, liposomes, nanoparticles, and so on The author, a pioneer of the field, invented the first artificial cells some 50 years ago and has continued to carry out active research in this field. Since then, there have been explosive research activities around the world on artificial cells, especially in fields related to biotechnology, nanomedicine, cell therapy, blood substitutes, drug delivery and others.  Based on his 50 years of work and an interdisciplinary background, the author has managed to include all those areas in artificial cells that are disguised under different terminologies. This is a very large area therefore each chapter begins by giving a detailed overview and  includes more than 1000 references to facilitate easier literature search of this highly interdisciplinary area.

 

Serpins constitute a superfamily of proteins that possess a unique tertiary structure and mechanism of proteinase inhibition. In humans, serpins constitute 10% of the plasma proteins and are best known as critical regulators of both the thrombotic and fibrinolytic systems. Serpins also participate in the regulation of the complement cascade, angiogenesis, tumor metastasis, apoptosis and innate immunity. Considering the importance of these molecules in regulating proteolytic cascades, it is not surprising to find that loss- and gain-of-function mutations result in significant human diseases
The goal of this text is to present the current knowledge on the molecular and cellular basis of serpins and their diseases.

Start date : 01/09/2007
Description : the laboratory UMR6153 of Cellular and Molecular electrophysiology and Imaging (University of Aix-Marseille) is looking for a lecturer. He/She will study plasticity of spinal and bulbar neurovegetative centers. Lectures concern animal physiology and functionnal neurophysiology, at L and M levels, will be given at Marseille and Aix.
Contacts :
André JEAN (Tel : 04 91 28 81 98 - andre.jean(a)univ-cezanne.fr)
Jérôme TROUSLARD (Tel : 04 91 28 91 69 - jerome.trouslard(a)univ-cezanne.fr)

The Myology Institute (Pitié-Salpêtrière hospital) is seeking a part-time or full-time physical therapist  (renewable temporary contract that could lead to a permanent contract) to perform quantified muscle force measurements within the framework of clinical research protocols for certain neuromuscular pathologies. Training given.
Contact : Jean-Yves HOGREL (Tel : 01 42 16 58 80 - jy.hogrel(a)institut-myologie.org)

Subject : Motor Unit Number Estimation (MUNE) and EMG decomposition: Application of Blind Source Separation (BSS) and comparison with other methods

Laboratory :
Institute Charles Delaunay - Troyes University of technology
Laboratory of Neuromuscular Physiology-Myology Institute, Paris
PhD supervisors: Jacques Duchêne (Troyes) and Jean-Yves Hogrel (Paris)

Application deadline : July 31, 2007
Contact Myology Institute : Jean-Yves HOGREL (Tel : 01 42 16 58 80 - jy.hogrel(a)institut-myologie.org)
Contact UTT : Jacques DUCHENE (Tel: 03 25 71 76 04 - jacques.duchene(a)utt.fr)

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.

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