Clinicians closed the morning session with a talk concerning therapeutic approaches for inflammatory myopathies. The afternoon was devoted to gene therapy with three seminars dedicated to techniques known as "gene surgery":  stop codon read through using antibiotics, the use of RNA in mitochondrial myopathies and exon skipping in Duchenne muscular dystrophy. 

Pr. Ketty Schwartz closed this workshop by emphasizing the multidisciplinary of the speakers. She also insisted on the importance of understanding fundamental disease mechanisms and was fascinated by the abundance of therapeutic approaches for neuromuscular diseases.

 

Olivier Boyer (CHU de Rouen, Inserm U519) et Olivier Benveniste (Hôpital Pitié Salpétrière, Paris)

The morning session was concluded by Dr. Olivier Boyer and Dr. Olivier Benveniste who gave a talk about the different therapeutic approaches that can be employed in inflammatory myopathies. They highlighted the need to develop animal models to understand the physiopathogenesis of inflammatory myopathies. 
They also presented two new preclinical models.

Terry Partridge (CNMR, Washington) et Luis Garcia (Généthon, France)
Pr. Terry Partridge and Dr. Luis Garcia terminated this session by discussing the promises, problems and perspectives of the exon skipping technique as a therapy for DMD. The aim of exon-skipping is to suppress the part of the gene containing the mutation in order to restore the reading frame and allow the cell to produce the missing protein. In about 75% of Duchenne patients, the mutation causes a shift of the reading frame leading to the synthesis of a non-functional dystrophin protein. The reading frame can be restored by artificially removing one or more exons directly before or after the deletion or point mutation from the mRNA. Exons can be eliminated from the mRNA with antisense oligonucleotides. Pr. Partridge presented data concerning the phase I clinical trial to be carried out by the Dutch biopharmaceutical company Prosensa. Repeated intramuscular injections of antisense RNA will be carried out at regular intervals. This is the first ‘in human’ trial of exon-skipping and will provide important proof-of-principle for total body systemic trials. Dr. Garcia talked about the impressive exon skipping results they obtained using an AAV vector to insert into the cell a small RNA from the cell nucleus known as U7. U7 masks the defective gene, thus restoring the reading frame within the cell. Due to potential immune reaction problems related to the use of AAVs in humans, especially as vaccins, alternative molecules are being considered. In particular, new synthetic RNAs, such as morpholino, which can achieve and maintain therapeutic levels of dystrophin throughout the body, will be employed (see article by J. Alter et al, Nature Medicine 2006 12(2):175-7).

Frédéric Mouquet (Hôpital Cardiologique, Lille)
To conclude this session, Dr. Frédéric Mouquet described the first cell therapy clinical trial in France for acute myocardial infarction termed, BONAMI: BONe marrow cells in Acute Myocardial Infarction. This study is headed by Professor Patricia Lemarchand at the University Hospital in Nantes and will involve a total of six different French institutions. The purpose of the study is to assess the effects of the injection of autologous bone marrow cells on heart repair after myocardial infraction. This randomised study has been underway since the end of December 2004 and should continue until the end of December 2006, with a final total number of 100 patients. Within a week to ten days of myocardial infarction, 100x10⁶patient's bone marrow cells are injected into the heart. This is a major innovation in cell therapy for the heart, especially since the restorative properties of bone marrow cells have been identified recently.