Therapeutics :

In the field of gene and cell therapies, 2004 was marked by the development of exon skipping – an innovative technique of gene therapy at present applied to Duchenne myopathy. The work was carried out in less than two years by Généthon, where the muscles of Duchenne myopathy mouse models were repaired. This was done by re-establishing the production of a truncated but functional protein. This new technique, which acts directly on the gene message, opens up prospects for numerous diseases.

In addition, the AFM has considerably stepped up its activities in the field of stem cells by : supporting the I-stem research programme (Institute of stem cells for the study and treatment of monogenic diseases), signing an agreement with the Cochin Institute for the study of somatic stem cells and contributing to the founding of the Biotherapy Research Institute in Montpellier.
These projects complement the research developed by the Généthon stem cell group since 2002 which itself continued the work begun by the AFM in 1998. The aim is to encourage work on these cells which, thanks to their capacity to be turned into different types of cells, are able to regenerate tissue and even organs.

Finally, in keeping with its policy of investigating promising new leads, in December 2007 the AFM supported a far-reaching research programme aimed at applying “genomic surgery” to the repair of genetic mutations responsible for rare pathologies. This technology is based on the use of particular enzymes (meganucleases) to repair specific mutations. Thus the AFM entered into partnership with Cellectis, a biotechnology company with unique expertise in the use of meganucleases for therapeutic ends. During 2008 the first start-up stages of this five-year project will consist of defining therapeutic targets then selecting and engineering the meganucleases so that they can then be tested and validated.

Creating the right conditions for the implementation of clinical trials for neuromuscular diseases in humans, requires tools that facilitate the preparation of the trials and the evaluation of the therapeutic effects.
AFM thus supports the development of molecular genetics databases (Institut Cochin, the Montpellier Institut de génétique moléculaire) : they cover genetic mutations and the clinical signs of each disease so that researchers can assemble homogeneous cohorts for their trials and patients can participate in therapeutic protocols which are adapted to the genetic anomaly in question.
To date, AFM has financed databases on Duchenne and Becker muscular dystrophy, Steinert, muscular dystrophy, Emery-Dreyfuss muscular dystrophy, laminopathies, dysferlinopathies, sarcoglycanopathies, calpainopathies, fukutine related protein muscular dystrophy, spinal muscular atrophy and myasthenia. The Association has also sponsored the development of a scale for Motor Function Measure, to help assess the motor capacities of patients affected by a neuromuscular disease. The validation protocol of this scale on 306 patients, which is particularly useful for the evaluation of the therapeutic effects, was completed in 2004.

Trials on humans have shown up certain obstacles that must be overcome in order to improve the effectiveness of treatments. For this reason the AFM supports research programmes that aim to reduce these obstacles. Here, the objectives are to :

- Improve vectors : vectors are the tools necessary to deliver therapeutics to the nucleus of the cells (in gene therapy, for example, by gene transfer or for gene surgery). Knowledge in this field - unknown less than 10 years ago - is becoming more sophisticated and the AFM is continuing its research at Généthon in Evry, but also in Nantes, Geneva and Barcelona.

- Disseminate treatments more widely in the affected tissues : in order to deliver the drug to the maximum possible number of cells, the dissemination methods of these therapeutics need to be worked on further, in particular by using the blood circulation system to repair a maximum of damaged tissue. A new method of gene transfer (a plasmid) by intravenous injection has been developed, with AFM support, by Prof John Wolf in the United States.

- Control the immune system better : the function of the immune system is to recognise and reject all elements foreign to the body and to thus form a real barrier to gene transfer or cell transplant. It is therefore vital to understand better how it functions. The know-how developed by Prof Brigitte Dreno at the University Hospital of Nantes, and supported by the AFM, has brought some extremely valuable insights in this field.

- Evaluate the effectiveness of therapeutic solutions : a treatment cannot be validated if it is not suitably evaluated. Thus it is necessary to design or improve tools capable of measuring the effects of these new therapies on the human body. In this effort, the AFM supports in particular access to and improvement of imaging techniques.

Thanks to the knowledge acquired over recent years in physiopathology and the molecular biology of the muscle and motoneuron, certain pharmacological treatments can now tackle not only the symptoms of the diseases, but their causes.

In addition, certain molecules exist which – although not offering a cure – can slow down disease progression and so help patients achieve the best state of health possible to face curative therapies.Thus, the AFM is supporting current or future clinical trials whose objective is to evaluate the effectiveness of these molecules in neuromuscular diseases.