The aim of this network is to synergize expertises from European basic researchers, leaders in their field, and European SMEs specialized in stem cell amplification and in safety of these procedures, to set up conditions for autologous transfer of human stem cells in GMP conditions for the treatment of DMD by exon-skipping. Cell therapy trials in DMD has never fulfilled the promises raised by the early results obtained in mouse models. Several groups have recently demonstrated the possibility of generating a truncated, but functional dystrophin using exon-skipping, by masking splicing sequences with oligonucleotides introduced by either direct or viral transfer.
The direct approach can be used as many times as needed, but is extremely expensive, while the AAV approach allows a large dissemination of the masking sequences, but triggers an immune response to the vector, and therefore can be used only once. Cell therapy can thus be used to target sites which have not been cured by the AAV approach, using autologous cells as vectors which, by fusing with the regenerating fibres of the patient, will bring a functional dystrophin to these fibres.
Myoblasts become progressively exhausted in DMD patients as the disease progresses, while stem cells, such as mesoangioblasts or AC133+, remain intact and functional. However, little is known either about the possibility to transduce these cells with oligonucleotides or vectors for exon-skipping, or the methods that can be used to expand these cells in GMP conditions. The technical and ethical guidelines resulting from this network will enable SMEs to expand stem cells with myogenic potential in GMP conditions for clinical trials in patients with DMD or other neuromuscular diseases. This network is a natural link between MYORES, an existing NoE dedicated to muscle research, and TREAT, an upcoming NoE dedicated to therapeutics (FP6 4th Call, line LSH-2005-2.1.1-7) since it gathers specialists belonging to both NoE.
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