Myology Institute : A flood of results with Telethon support :

With no less than 8 publications in major international scientific journals in just a few weeks, Institut de Myologie (Myology Institute) research teams* have demonstrated their leading role in the progress of knowledge and the fight against neuromuscular disease. Resulting from years of work and investments made possible by Telethon donations, some of these results are helping to improve understanding of the diseases, while others provide innovative research tools and prepare future clinical trials.

*Research teams at the Myology Institute since 1st January 2009:
(1) UMRS974 INSERM-UPMC-CNRS-AIM: "Thérapie des maladies du muscle strié" (Treatment for Striated Muscle Diseases) directed by Thomas Voit
(2) UMRS787 INSERM-UPMC-AIM: "Groupe Myologie" (Myology Group) directed by David Sassoon

1 – New treatment prospects

•Myostatin inhibition does not affect muscle stem cell
Helge Amthor's team (UMRS 974), in cooperation with English and American teams, has demonstrate that, contrary to what was believed until now, inhibition of myostatin (a factor which normally limits muscle growth) has no harmful effects on satellite cells (cells which are essential for repairing injured muscles). These results shed new light on treatment systems involving myostatin blockage. PNAS, published on-line on 21 April 2009.

•Bone marrow finally within reach for gene therapy
One of the major challenges of gene therapy for diseases affecting the nervous system lies in the contribution of gene therapy as far as motor neurons and bone marrow. Through work conducted by Martine Barkats (UMRS 974/ CNRS FRE 3087, Genethon) and her colleagues in the Biotherapy for neuromuscular diseases team, this obstacle is now being overcome. These researchers have just shown that in adult animals, an AAV vector, in this case AAV9, can transduce the central nervous system, probably partly by crossing the blood-brain barrier which isolates the central nervous system – brain and spinal cord – from the blood circulation, in adult mice. Furthermore, and in cooperation with INSERM unit U649 led by Philippe Moullier in Nantes and the Nantes Veterinary School, these researchers have shown that this methodology is applicable to large animals, in this case the cat used as a model of spinal amyotrophy. Molecular Therapy, 14 April 2009, published on-line.

•Hurler's syndrome: evaluation in primates of the biodistribution of vectors anticipated for use in gene therapy
The results of a study performed by INSERM unit U649 led by Philippe Moullier in Nantes and the Nantes Veterinary School, in cooperation with Martine Barkats (UMRS 974) of the Biotherapy for neuromuscular diseases team, show that the three vectors evaluated are distributed equally throughout the brain and spinal cord in primates and two of them could be more effective. Human Gene Therapy, April 2009, vol. 20 No. 4, pp. 350-360, published on-line on 9 March 2009.

2 – Towards better understanding of diseases

•Steinert's disease: premature ageing of satellite cells
Denis Furling (UMRS 974) and his colleagues of the Remodelling, regeneration and cell therapy for striated muscle team have revealed the involvement of satellite cells in type 1 myotonic dystrophy. They have discovered that in patients, these cells undergo premature ageing which could contribute to the gradual atrophy of their muscles. American Journal of Pathology, No. 174, pp. 1435-1442, published on-line on 26 February 2009.

•The neuromuscular junction involved in autosomal dominant Emery-Dreifuss muscular dystrophy
The Genetics and physiopathology of neuromuscular diseases team led by Gisèle Bonne (UMRS 974), in close cooperation with Tom Misteli's American team (NIH, Washington) and particularly with Alexandre Méjat, has just demonstrated in two mouse models of this disease, that faults in the neuromuscular junction form part of the mechanisms leading to the development of this disease. Journal of Cell Biology, vol. 184, No. 1, pp. 31-44, published on-line on 5 January 2009.

3 – Research tools

•A mouse model of polymyositis confirms the therapeutic benefit of Tregs
Work conducted by the Remodelling, regeneration and cell therapy for striated muscle team lead by Gillian Butler-Browne (UMRS 974 & UMRS 787) has resulted in teams led by Prof. Olivier Benveniste and David Klatzman (Pitié-Salpêtrière) developing mouse models of polymyositis and testing a new therapeutic approach. They have confirmed the therapeutic potential of regulator lymphocytes (Treg). American Journal of Pathology, No. 174, pp. 989-998, published on-line on 13 February 2009.

•An inexhaustible source of muscle stem cells to help researchers
The Remodelling, regeneration and cell therapy for striated muscle team in cooperation with the Biotherapy of neuromuscular diseases team led by Luis Garcia (UMRS 974) has developed a technique for obtaining a virtually inexhaustible source of muscle cells, with a view to validating therapeutic strategies used for neuromuscular diseases. Human Gene Therapy, published on-line before printing on 9 April 2009.

•A new method for producing cardiac tissue
Until now, obtaining cardiac tissue meant using products from tumours, which could not therefore be used in humans. Catherine Coirault and her colleagues in the Genetics and physiopathology of neuromuscular diseases team (UMRS 974) have just developed a method which avoids using these toxic products and could eventually be adapted to skeletal muscle. Nature Clinical Practice – Cardiovascular Medicine, March 2009, vol. 6, No. 3, pp. 240-249.

The Myology Institute in brief :

Created in 1996 by the Association Française contres les Myopathies (AFM - French Muscular Dystrophy Association) through Telethon donations, the Institut de Myologie (IDM - Myology Institute) is an international research centre on muscles and muscular diseases, operating at the Pitié-Salpêtrière hospital. It includes, on a single site, complementarity activities in close partnership with Inserm, AP-HP, UPMC (Pierre and Marie Curie University) and the CNRS: treatment, research, teaching and community activities to understand muscle, its function, pathologies, ageing and how to treat it. It brings together nearly 250 researchers, physicians, students and related staff over more than 5,000sq.m of laboratories. 22 clinical protocols are in progress there. Overall support from the AFM and IDM reached nearly €7million in 2008. For further information : www.institut-myologie.org