Cell mediated gene therapy for muscular dystrophy: steps towards clinical efficacy.

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This research aims to optimise a treatment that was recently tested in patients affected by Duchenne muscular dystrophy and extend it to another rare genetic diseases of the muscle, so that one strategy may in the future be adapted for more diseases. Muscular dystrophies are caused by mutations in a single gene that leads to the impairment of function and death of muscles in the human body. This in turn causes disability of variable severity that, in the worse cases, are devastating; compromising quality of life and leading to a premature death. Although individual muscular dystrophies are rare or extremely rare, together they affect many thousands of people and represent a major challenge for National Health Services, in charge of providing palliative therapies and medical assistance, often over decades. In order to "cure" genetic diseases it is necessary to replace or repair the defective gene and this can be achieved by using viral vectors (viruses that have been modified in the lab to deliver a correct version of the gene into cells) or stem cells (cells which can be used to generate any other type of cell in the body). To make sure they're accepted by the body, stem cells can be derived from a related donor (e.g. a sibling) or from the patient themselves, after having been "repaired" in the lab. These therapies have been successful so far for several genetic diseases affecting the blood, the skin, and the cornea. This has been possible because it is relatively easy to remove the diseased tissue and replace it. This approach is not possible for diseases affecting the heart, the liver or the brain. In these cases, healthy cells will have to correct the genetic defect and somehow help the function of the resident diseased cells.The innovative aspect of our treatment is based on the fact that stem cells which are injected into the arteries of patients end up distributed uniformly throughout the body. Some of these stem cells can then cross out of the blood vessel, move into the surrounding tissue of the body and eventually repair it. However, the process is not yet efficient enough to result in a noticeable improvement in patients. In order to achieve this, we will study in detail each step of the transplantation procedure through a number of culture system using human stem cells. The successful completion of the research programme will rapidly lead to new clinical trials and then may be extended to more rare genetic diseases of muscle, increasing the benefit to patients.