Muscular dystrophy stem cell hope

A new way to manipulate human embryonic stem cells (ESCs) offers hope of a treatment for muscular dystrophies. The muscle-wasting conditions are caused by genetic mutations which block production of a key protein in cells.

In theory, ESCs could be used to replace defective cells - but getting them to form muscle cells in sufficient quantity has proved difficult. Nature Medicine details US work using genetic manipulation to overcome the problem, with positive results in mice. However, much work is required before the technique can be tested in humans.

The genetic mutations that cause muscular dystrophy - of which Duchenne muscular dystrophy is the most common - lead to loss of production of a key structural protein of muscle cells called dystrophin. When this occurs the cells can no longer regenerate after injury, resulting in progressive muscle weakness and eventual death.

Currently there is no effective treatment for muscular dystrophy. Scientists have tried to develop ways to transplant muscle cells called myoblasts to replace the faulty cells. But attempts have failed because the cells do not survive well, and have a limited ability to migrate to the areas where they are most needed.

Researchers believe that ESCs may provide a more adaptable alternative source of replacement cells - but until now it has proved difficult to produce them in sufficient number to have any therapeutic effect. In the latest study, a team at the University of Texas Southwestern used genetic manipulation techniques to stimulate the production of a key chemical inside ESCs that triggers their transformation into muscle cells, followed by cell sorting to purify the muscle-forming cells.

This led to the creation of enough partially-formed new muscle cells to potentially have a real therapeutic impact on mice. The cells were then delivered to the muscle either through direct injection, or intravenous infusion, and the researchers measured significantly improved muscle function in the animals, the first time such a result has been obtained using ESCs. They also say that because the cells were highly purified when introduced to the mice, the risk of tumour formation - another problem with previous attempts to use ESCs - was eliminated. They accept that at least a decade's work is still required to refine the technique before it can be applied in clinical trials.

Dr Marita Pohlschmidt, director of research at the Muscular Dystrophy Campaign, said: "Embryonic stem cell technology has the potential to become a powerful tool to treat a number of muscular dystrophies and related conditions. The results presented in this paper are promising because they demonstrate that embryonic stem cells can develop in to muscle cells when injected into an animal model. However, this area of research is still in its infancy and much more work must be done before stem cell technology can be regarded as a viable route for treatment of muscle disease."