The Institute of Myology was established to fill the needs of the AFM, of patients and their families and to set up in public hospitals a reference centre that includes medical specialists, basic and clinical research teams and education curriculum on muscles and their pathologies. The AFM’s mission is to stimulate innovative clinical research by helping conduct clinical trials and by financing part, or all of them. Each year the AFM launches a call for proposals dedicated to the development of therapeutics. This program may concern the development of therapeutic products, or preclinical and clinical trials. All projects are evaluated by the Scientific Council. In order to provide an impetus to clinical trials, the AFM has created a service whose role is to identify innovative scientific strategies, stimulate and monitor projects. For example, as a result of studying the potential of cell therapy in FSHD, the AFM received several preclinical research proposals in this field. The AFM’s role then consists in helping those teams who wish to elaborate their projects before they are submitted to the Scientific Council during the call for proposals period.
The AFM is funding nearly 40 clinical trials that are either in preparation or in progress, including about twenty trials at the Institute of Myology which concern both the natural history of genetic muscular disease and pharmacological, cell, gene and enzyme therapies as well as effort retraining.
Besides the trials investigated directly by teams from the Institute of Myology, the AFM or Généthon, the technological and scientific platform of the Institute is recognised by well-known organisations (NIH; Genzyme) which have chosen it for some of their trials.

Loss of muscle strength is one of the key features in diseases such as amyotrophic lateral sclerosis (ALS) and Duchenne muscular dystrophy (DMD) and accurate evaluation of muscle strength is crucially important. In this article, Dr. Jean-Yves Hogrel from the Institute of Myology and his colleagues describe the development of a normative database for isometric strength measured by quantitative muscle testing (QMT) for a French adult population. The study included 315 healthy men and women from four clinical centres treating patients with neuromuscular disorders. Strength measurements for 14 muscle functions (13 bilaterally and neck flexion) were performed. In 86% of patients, the right side was dominant and significantly stronger (P<0.05) for all muscle functions except hip flexion and extension, knee flexion and shoulder internal rotation. A predicted strength value for each muscle group could be computed for a patient of any age, sex and height. Compared to published normative data from the U.S. population, with the exception of hip extension, significantly lower values were observed in the French population. The predictive values deduced from the French regression models were also lower than the American predictive values. This database will allow objective evaluation of patients with respect to these normative data, assessment of the degree of their neuromuscular deterioration and collection of information on the clinical course of the disease. Furthermore, composite scores can be estimated in therapeutic trials to follow a global index of strength.
Arch Phys Med Rehabil. 2007 Oct;88(10):1289-97.

Defects in glycosylation of alpha-dystroglycan are associated with several forms of muscular dystrophy, often characterized by congenital onset and severe structural brain involvement, collectively known as dystroglycanopathies. Six causative genes have been identified in these disorders: POMT1; POMT2; POMGnT1; fukutin, FKRP and LARGE. The increased availability of mutation analysis in patients with a dystroglycanopathy has consequently led to the discovery of a range of phenotypes resulting from mutations in FKRP. However, there is no data concerning the frequency of involvement or the genotype-phenotype relationships for the other five genes in a large and unbiased population. In this study, the authors have systematically screened a large population of 92 unrelated individuals with a dystroglycanopathy phenotype for mutations in POMT1; POMT2; POMGnT1; fukutin and LARGE genes. Mutations were observed in 34% of these patients. Mutations in the FKRP gene had previously been excluded. Mutations in POMGnT1 and fukutin were associated with a wider than reported spectrum of clinical severity. The majority of patients with POMT1 and POMT2 mutations have evidence of central nervous system involvement. Only one patient presented a mutation in the LARGE gene. In decreasing order of prevalence, mutations in the glycosyltransferase genes were as follows: POMT2; POMT1; POMGnT1; fukutin and LARGE. The data presented in this paper increase the clinical spectrum of disorders associated with mutations in the known glycosyltransferase genes.

Muscle-eye-brain disease (MEB; OMIM 253280) was first described in 1977 in Finland, where it is enriched because of founder effect and genetic isolation. MEB is now known to occur throughout the world, but Finland remains the country with the largest group of MEB patients. It is an autosomal recessive disorder characterized by congenital muscular dystrophy, brain malformation and ocular abnormalities. MEB is caused by mutations in the protein O-linked mannose ß1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) gene. To date, 28 different POMGnT1 mutations have been identified with a diverse clinical spectrum. In this paper, Dr. Ute Hehr and her colleagues describe the clinical, neuroradiological and molecular genetic findings in nine MEB patients from eight independent families of various ethnic origins. The authors aimed to further characterize the spectrum of identified human POMGnT1 mutations and to investigate a possible genotype-phenotype correlation. The age at the time of clinical examination varied between 3 months and 16 years. Psychomotor and mental development indicated moderate to severe global retardation. At birth, all patients presented a severe muscular hypotonia with distinctly elevated CK values. Ophthalmologic findings revealed a wide array of abnormalities in all patients, resulting in severe visual impairment, the most frequent being sever myopia. Out of five cases, prenatal ultrasound data revealed a hydrocephalus in four patients. The most prominent and consistent feature observed on cerebral MR images was marked alterations of the white matter, including hypoplasia of the brainstem with a characteristic flattening and kinking of the pons. Hydrocephalic changes of varying degree and thinning of the corpus callosum were also observed in this patient cohort. Concerning molecular genetic findings, three previously reported and six novel POMGnT1 mutations were identified. The combined data from this study allowed the authors to conclude that there is no genotype-phenotype correlation for POMGnT1-confirmed MEB patients and that additional environmental and/or genetic factors may contribute to the observed clinical variability of POMGnT1-associated phenotypes.

Asklepios BioPharmaceutical, Inc., (AskBio) has announced the creation of the Chapel Hill Project, a non-profit organisation created to further development of cell and gene therapies for orphan diseases. Askbio will provide the Chapel Hill Project with access to its Biological NanoParticle (BNP) and Self-Complementary Vector technologies with no up-front cost. The Chapel Hill Project will make this technology available to researchers for use in developing novel treatments for orphan disease indications. The Chapel Hill Project hopes to eventually serve as a depository for intellectual property that can be used for the development of cell and gene therapies for orphan diseases with other companies contributing the use of their DNA-based technologies in order to speed the advancement of orphan disease therapeutics to the market. Recombinant adeno-associated virus (rAAV) has become a successful gene-delivery vector for a multitude of targets due to its "non-pathogenic properties and absent immune response, ability to maintain efficient and long-term expression, and ease of genetic manipulation". AskBio has developed a library of rAAV Biological Nano Particles.

The congress was dedicated to three groups of neuromuscular diseases: metabolic myopathies, congenital muscular dystrophies and congenital myopathies. As usual, the final day was devoted to therapeutic approaches. Thomas Voit, Scientific Director of the Institute of Myology and member of the WMS programme, shares his impressions of the event.

 

As a member of the WMS programme committee, were you fully satisfied with the congress, in terms of the organisation or scientifically?
I wouldn’t say that I was 100% satisfied but that’s related to my character. On the whole, the congress went very well, especially given the number of participants. There was a particular problem during the poster session, which was inconvenienced by the excessive number of both people and posters. Next year, we will improve or at least change the way posters are presented. This is part of the various changes that we would like to implement next year so that the WMS congress regains its more intimate character and thereby stimulates collaboration.

The Symposium is planned as two parallel meetings, one on biomedical science and the other on research and advances in the care and management of people affected by ALS/MND. Joint sessions consider issues of mutual concern, challenging current views and practice.

This year's MYORES Congress will be combined with the mid-term review. As you can see in the (preliminary) program, the first 1,5 days (Monday, December 17th and Tuesday, December 18th) are only for MYORES members and are not open for the public. The lab-heads should come with one student/postdoc (who is working on the most important MYORES-project) and the person who is responsable for the platform.

Cell and molecular Biology have made tremendous strides over time. Inputs from physical scientists especially in the area of structural biology has added a great deal of information to our knowledge base of interrelationship between structure and function. Structure can be manipulated to modulate a function or create a new function. In today's post genomic era proteomes are well analysed thanks to the advent of several kinds of mass spectrometers. However, in spite of these advances we have only partial understanding of complex processes like cell growth, cell cycle, cell proliferation, cell differentiation inter- and intra-cellular trafficking and apoptosis. The International Congress on Cellular and Molecular Biology will focus on life processes that are least understood.

Contact: Professor Baishnab C Tripathy, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Email: baishnabtripathy(a)yahoo.com

Scientists from around the world will gather to exchange ideas about cutting-edge research on the human embryonic stem cells. With a lineup of 29 fascinating Lectures from selected specialists, including dedicated sessions for industrial applications of human ES cells and presentation of scientific networks supported by the European Commission, FISH-ESC 2008 is an opportunity for learning and professional development not to be missed.

The symposium will include sessions on:
The peripheral nervous system, neuroimmunology, aging, neurodegenerative diseases and dementia. Hands-on' workshops such as the interpretation of laboratory tests in neurological disease will also take place.

Trophos SA, a biopharmaceutical company specializing in the discovery and development of drugs for neurological disorders, announced that the company has begun enrolling Spinal Muscular Atrophy (SMA) patients in a Phase Ib clinical trial of its lead product, TRO19622. The clinical trial will involve 20 type 1b-3 SMA patients aged between 6-25 years of age and will assess the pharmacokinetics and safety of drug product after administration of single and multiple doses, once-daily, by the oral route. The study is being conducted at three centres in France.
The clinical program in SMA is supported by the Association Française contre les Myopathies (AFM), through a strategic partnership begun in 2000.
Thanks to Téléthon donations, over the last 7 years Trophos has received decisive financial support from the AFM for this project. Now, barely four years after the identification of a candidate molecule, a clinical trial in humans is underway. This again shows how a patient association can play a leading role in promoting drug development.

The idea that the adult brain of mammals can generate new neurons has only recently been accepted by the scientific community, and research in this exciting area is now in full swing. Bringing together leading researchers in the field of adult neurogenesis, the 30 chapters in this monograph provide a valuable overview of this emerging field and lay the groundwork for future studies. Adult Neurogenesis includes discussions on neural stem cell biology; methods and models for studying adult neurogenesis; physiological and molecular processes and their control; related neurological diseases; and comparisons of neurogenesis in humans, birds, fish, and invertebrates. It will be of interest to all researchers in neurobiology as well as those in the medical field, as it has implications for understanding depression, epilepsy, and other psychiatric disorders.

Research into the causes of aging, and strategies to delay that process, have gained much ground and attention in recent years. This volume covers the major threads in the molecular genetics of aging, including genes that regulate aging, causes of aging, evolutionary theories of aging, and the relationship between diet and aging. Among specific topics covered are calorie restriction, mitochondria, sirtuins, telomeres, stem cells, and cancer. Each chapter is written by one or more leaders in the field, and the book presents the current status of this exciting research area and provides an invaluable source of information in a single volume.
> Molecular Biology of Aging

Department of Human Genetics, based at the Leiden University Medical Centre, Leiden, The Netherlands

The Department of Human Genetics is looking for a post-doctoral researcher for its team investigating new therapeutic strategies for patients with Duchenne muscular dystrophy.

 

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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