Community Research and Development Information Service - CORDIS


MYOAMP — Result In Brief

Project ID: 37479
Country: France

Exon skipping for muscle repair

European researchers have investigated the ideal conditions for amplification of muscle stem cells to be used in cell therapy for patients with Duchenne muscular dystrophy (DMD).
Exon skipping for muscle repair
As many as 30,000 young people are affected by DMD in Europe. At the core of this debilitating disease lies the dystrophin protein that sits in the membrane surrounding the muscle protecting it from damage on contraction.

Patients with any of the muscular dystrophies can have a faulty dystrophin gene where parts, known as exons, are missing. Eventually, after repeated damage, particularly in DMD – the most severe form of the disease – the muscle fibres die. One possible answer is so-called exon skipping during muscle protein production. This involves literally skipping over the faulty exon(s) so a form of the muscle is made – better than muscle that is completely non-functional, the case in DMD.

To implement exon skipping, a piece of imported genetic material, a molecular plaster, must be 'stuck' over the gap in the faulty gene. This enables the machinery that makes the muscle from the gene information to skip to the next part. Prior research has not been able to put this into practice but the solution may lie in using muscle stem cells (myogenic progenitor cells (MPCs)) from the individual's own cells in autologous cell therapy.

The EU-funded 'Amplification of human myogenic stem cells in clinical conditions' (MYOAMP) project addressed the question of how to amplify MPCs as well as address safety and ethics issues. To improve understanding of regulation of proliferation including the mitotic clock status of the cells, in vitro and in vivo trials were run.

MYOAMP scientists also investigated the number of cells needed on injection at each implantation and defined the maximum number of cells to be amplified in good manufacturing practices (GMPs). The researchers also drew up guidelines for production of MPCs in GMP conditions and stability of the parameters during amplification.

Definition of protocols to obtain amplified human myogenic stem cells with optimised efficiency in clinical trials is a major step forward for research into DMD. Moreover, as stem cell multiplication is at the basis of many of the new genomic-based therapies, the technology would be potentially applicable across a wide range of biomed disciplines.

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