Newsletter :: Institut de Myologie |
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 | Bimonthly Newsletter - February / March 2009
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Edito  THIS issue of the Newsletter features an interview with Dr. David Sassoon, one of the ‘elite foreign research scientists’ selected by the French Ministry of Research to reinforce France’s potential of innovative research on an international level. From the sound of things, he appears to be reaching his goal following the recent 4-year renewal of his research unit, UMR S 787 Myology Group. MARC Bitoun, a researcher from the Institute of Myology also participated in this Newsletter by describing the results of a recent publication from the Institute that highlight the identification of a new mutation in the dynamin 2 (DNM2) gene associated with a particular form of centronuclear muscular dystrophy are described. AS always, our newsletter offers you information about upcoming events, latest national and international research highlights, and new publications from research teams at the Institute. RNC |
3 questions for David Sassoon, Director of UMR S 787 Myology Group
UMR S 787 Myology Group consists of 4 research teams led by D. Sassoon & G. Marazzi, F. Relaix, E. Gomes and A. Ferreiro. Just 18 months after its creation, the unit was reviewed and is now renewed for 4 years.
How does the Myology Group operate?
As a condition for my coming to France, my project was to build a research structure built around elements that function independently. This may seem paradoxical, but this is the key ingredient for generating top level research—let me explain :
Each team leader works with his or her group on topics that they propose and for which I do not intervene nor do I take credit for their work (such as signing papers, etc.). In parallel, the teams, as chosen, are complementary in terms of research interests that relate to the entire research unit. At the end of the day, this very autonomy has led to collaborations between teams to address questions that would be difficult to examine as individually. Collaboration and autonomy are to key ingredients that define my research unit.
Each team leader works with his or her group on topics that they propose and for which I do not intervene nor do I take credit for their work (such as signing papers, etc.). In parallel, the teams, as chosen, are complementary in terms of research interests that relate to the entire research unit. At the end of the day, this very autonomy has led to collaborations between teams to address questions that would be difficult to examine as individually. Collaboration and autonomy are to key ingredients that define my research unit.
Zoom on a publication from the Institute
Since 1 January 2009, Marc Bitoun is a researcher in the group of Gisèle Bonne, UMR 974, Institute of Myology. He and his colleagues have just published an article in the journal Neurology, concerning the identification of a new mutation in the dynamin 2 (DNM2) gene associated with a particular form of centronuclear muscular dystrophy. This work was carried out in the group of Pascale Guicheney (formerly Inserm U582).
What is this new mutation that you describe in your article?
This mutation that affects dynamin 2 (DNM2) has two peculiarities. Firstly, it is located in the middle of a group of mutations that induce neuropathies. Therefore, the position of the mutation does not produce the associated phenotype; in this situation, there is no genotype-phenotype relationship. Secondly, the mutation is associated with a form of the disease intermediate of severe forms that occur in children and mild forms observed in adults.
> Access Marc Bitoun's complete interview
This mutation that affects dynamin 2 (DNM2) has two peculiarities. Firstly, it is located in the middle of a group of mutations that induce neuropathies. Therefore, the position of the mutation does not produce the associated phenotype; in this situation, there is no genotype-phenotype relationship. Secondly, the mutation is associated with a form of the disease intermediate of severe forms that occur in children and mild forms observed in adults.
> > Access all our online interviews
AVI publishes latest Exon skipping clinical trial results
The latest results of a study released by AVI BioPharma Inc, a developer of RNA-based drugs, demonstrate that Duchenne Muscular Dystrophy (DMD) could be treated successfully by exon skipping. DMD is an incurable muscle-wasting disease associated with errors in the gene that makes dystrophin, a protein that plays a key structural role in muscle fibre function. The clinical trial of the drug AVI-4658, developed by AVI BioPharma, was led by Professor Muntoni at UCL Institute of Child Health London. Biopsy data showed that injection of the drug into the foot muscles of a series of Duchenne patients successfully induced new dystrophin production. Furthermore, the drug was well tolerated, with no significant detectable drug-related adverse events. The drug candidate AVI–4658 is designed to skip exon 51 of the dystrophin gene, allowing for restoration of the reading frame in the mRNA sequence. Restoration of dystrophin production achieved by skipping this exon may potentially improve or significantly slow the disease process, thus prolonging and improving the quality of life for the affected patient. These early results that show exon skipping therapy can be a potential treatment for DMD is promising news that will be welcomed by all sufferers and their families. Recruitment of Duchenne patients for a further AVI-sponsored trial to see if this drug can be delivered body wide is now underway. The trial, which was opened in December 2008, will administer AVI-4658 systemically to see if dystrophin can be produced in all muscles. It is hoped that this might slow the very severe progression of the disease.
> Read the Press Release
Molecular therapy for spinal muscular atrophy closer to clinical use
Spinal Muscular Atrophy (SMA), a neurodegenerative disorder, is caused by the loss of survival motor neuron 1 (SMN1) and is the leading genetic cause of infantile death. In humans two copies of the SMN gene exist, SMN1 and SMN2. The critical distinction between the two genes occurs at the RNA processing level: SMN1 produces full-length transcripts, while SMN2 primarily produces an alternatively spliced transcript lacking the final coding exon. Thus SMN2 alone cannot compensate for the loss of SMN1. SMN2 is retained in essentially all SMA patients and is a primary target for SMA therapeutic development such as trans-splicing. Trans-splicing therapy relies on splicing of mutant RNA and therapeutic RNA in order to correct RNA sequence. As a therapeutic approach, trans-splicing offers the advantage over gene replacement in that the endogenous promoter intrinsically controls expression. Consequently, temporal and spatial constraints on gene expression are retained. While this form of molecular therapy has had impressive results as a treatment for spinal muscular atrophy in cell-based models of disease, scientists have been unable to translate the therapy to humans. In this article, researcher from the University of Missouri have developed a strategy that will enhance trans-splicing activity and bring it closer to being used in the clinical setting. To improve efficiency, a series of antisense RNAs were screened to identify a sequence that would disable SMN exon 8 and promote trans-splicing. Inactivating the gene reduces competition at splice sites and improves the likelihood of achieving the desired results. In vitro assays identified an enhancing antisense RNA and were constructed into a novel single vector system individually expressing the trans-splicing RNA and the antisense RNA. Cell-based assays identified a highly efficient vector system that resulted in high levels of trans-splicing and correspondingly high SMN protein levels and increased SMN activity in SMA-derived extracts. This strategy provides insight into the trans-splicing mechanism and significantly improves trans-splicing activity in a mouse model of spinal muscular atrophy, demonstrating a platform that can significantly elevate SMN levels in vivo and in a relevant disease context.
PLoS ONE. 2008;3(10):e3468. Epub 2008 Oct 22.
The XI Myogenesis Symposium
2 & 3 February 2009, Paris
2 & 3 February 2009, Paris
The XI “Myogenesis Symposium” organized by P. Maire and C. Marcelle was held on the 3 and 4 of February at the Institute of Myology in Paris. This meeting gathered 140 researchers from different French laboratories working in the muscle field. The presentations covered various areas such as stem cells, development, cell signalling and muscle diseases.
The next meeting will be held in Cassis June 18-19
> Download the abstracts (PDF - 25 pages - 294 kb)
Discover our selection of scientific and medical publications in the fields of myology and neuromuscular diseases: a summary of each publication aimed at the general reader, highlighting the main points of the article and the authors’ conclusions is provided.
- Mutations in BAG3: Identification of a novel severe autosomal dominant childhood muscular dystrophy - Read
- Laminin-111 shows potential for congenital muscular dystrophy - Read
- Necklace fibres: an unusual histological pattern of centronuclear myopathy - Read
- Neuromuscular defects in Emery-Dreifuss muscular dystrophy - Read
June 21-23, 2009 - Paris, France
Abstract submission deadline: March 15, 2009
Registration deadline: June 10, 2009
> Preliminary programme
July 9-11, 2009 - Atlanta, USA
September 9-12, 2009, Würzburg, Germany
Deadline for handing the abstracts is April 30, 2009
> For more information
Recent publications from the Institute
"Necklace" fibers, a new histological marker of late-onset MTM1-related centronuclear myopathy.
Acta Neuropathol, 2009, 117 (3):283-91. Epub 2008 Dec 16.
Differential involvement of sarcomeric proteins in myofibrillar myopathies: a morphological and immunohistochemical study.
Acta Neuropathol, 2009, 117 (3):293-307. Epub 2009 Jan 17
Anticorps dans la myasthenie.
Rev Neurol (Paris), 2009, 165 (2):137-43. Epub 2009 Jan 21.
Remaniements experimentaux et pathologiques de la jonction neuromusculaire.
Neurochirurgie, 2009, 55S1:S104-S109
Analysis of the DYSF mutational spectrum in a large cohort of patients.
Hum Mutat, 2009, 30 (2):E345-75
A mutation in the SEPN1 selenocysteine redefinition element (SRE) reduces selenocysteine incorporation and leads to SEPN1-related myopathy.
Hum Mutat, 2009, 30 (3):411-6
Periodic variation in R-R intervals and cardiovascular autonomic regulation in young adult Syrian hamsters.
Am J Physiol Regul Integr Comp Physiol, 2009, 296 (3):R610-7. Epub 2008 Dec 24.
Comparison of toxicity and transfection efficiency of amphiphilic block copolymers and polycationic polymers in striated muscles.
J Gene Med, 2009, 11 (3):240-9
Press releases
- Gene therapy - Production of the first batch of HIV-derived vectors in Europe for use in a human clinical trial
Généthon, the laboratory created and funded by the AFM (French Association against Myopathies) using donations from Téléthon, today announced that it has produced, controlled and released a batch of lentiviral vectors derived from the human immunodeficiency (HIV) virus for a gene therapy trial in humans in a rare immune deficiency. The Etablissement de thérapie génique et cellulaire (ETGC – gene and cell therapy unit) at Généthon thus becomes the first organisation in Europe to have produced this type of vector in accordance with GMP (good manufacturing practice) standards. Part of the safety controls were carried out by GenoSafe , a company created by the AFM and Généthon.
> Access the complete press release - 2 pages - 91 ko
> Access the complete press release - 2 pages - 91 ko
- Carnitine palmitoyltransferase II deficiency - Bezafibrate effective in the treatment of this mitochondrial myopathy
A team of researchers and hospital doctors coordinated by Fatima Djouadi, a senior research officer at Inserm, and Jean-Paul Bonnefont, has just demonstrated the potential benefit of Bezafibrate, a product already widely used as a lipid-lowering drug, in the treatment of a metabolic myopathy: Carnitine Palmitoyltransferase II (CPT2) deficiency. This first clinical trial has demonstrated that treatment with bezafibrate for a period of six months stimulates the metabolic functions of the muscles and leads to an improvement in physical activity capacities and a reduction in muscle pain.
> > Access all our press releases
Book
- The Origin of Individuals : A Darwinian Approach to Developmental Biology
by Jean-Jacques Kupiec
This book presents a new approach to biological systems based on cellular Darwinism. Genes are ruled by probabilistic mechanisms allowing cells to differentiate stochastically. Embryo development is not governed by a determinist genetic program but by natural selection occurring among cell populations inside the organism. This theory has considerable philosophical consequences. Man may be a machine but he is a random one. This book is suitable for researchers, students and lay readers interested in biology, especially embryogenesis.
MRC Career Development Fellowship – Muscular Dystrophy research
A post-doctoral position is available in Professor Kay Davies’ group at the MRC Functional Genomics Unit.
The post holder will join an active research team working on the analysis of the dystrophin associated protein complexes in muscle and nerve and the function of the synapse. The long term goal is to characterise components of these complexes and proteins at the neuromuscular junction which might shed light on dysfunction in human disease. The successful applicant should have a background in molecular / cell biology. Experience of confocal microscopy, immunoprecipitation and tissue culture would be an advantage, although training will be given.
The Unit is embedded within the Department of Physiology, Anatomy and Genetics at the University of Oxford and is a world-renowned centre for research into neuromuscular and neurodegenerative disorders. We offer excellent laboratory facilities in the recently opened Henry Wellcome Building of Gene Function. Additional information about the Unit can be found at www.mrcfgu.ox.ac.uk.
This is a 3 year training and development position for a post-doctoral scientist who has either just completed their doctoral studies, has no previous experience of key transferable skills, is moving into a new research discipline, or is clinically qualified with little or no research experience. It provides opportunities to develop research project skills and develop collaborative links with colleagues within the University of Oxford and elsewhere. Additional benefits include 30 days annual leave and an excellent pension scheme. Starting salary will be from £25,622 per annum.
Applications for this role must be made online at http://jobs.mrc.ac.uk. Please ensure you include a copy of your CV, covering letter and contact details for three professional referees within your application. If you do not have internet access or experience technical difficulties, please call 01793 301049, quoting reference number FGU09/078.
> For further information about the MRC please visit www.mrc.ac.uk.
Closing date for applications: 17 March 2009.
The MRC is an Equal Opportunities Employer.
> For further information about the MRC please visit www.mrc.ac.uk.
Closing date for applications: 17 March 2009.
The MRC is an Equal Opportunities Employer.
Discover our selection of scientific and medical publications in the field of myology and of neuromuscular diseases.
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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| Editor-in-chief : Samia Ghozlane Editor : Anne Berthomier; Racquel N. Cooper. Editorial Board : Serge Braun; Monique Karkatcharian; Stéphane Roques; Thomas Voit; J. Andoni Urtizberera. Contact us – © 2009 – AFM-Institut de Myologie. All rights reserved. | |
