Stem cell therapy treats muscular dystrophy in mice

Researchers at the University of Texas Southwestern Medical Centre have developed a new technique to treat the symptoms of muscular dystrophy using embryonic stem cells (ES cells). The group, reporting in the February 2008 issue of Nature Medicine, successfully manipulated mouse ES cells to transform them into muscle-forming cells. They then transplanted these cells into mice that have the same genetic disorder that causes Duchenne muscular dystrophy (DMD) in humans.

DMD is the most common of nine muscular dystrophies. It is caused by a defect in a protein called dystrophin, which is vital to muscle regeneration - without it, muscles are unable to renew after injury. This results in the progressive and eventually fatal muscle wasting that characterises DMD. After treating the dystrophin-lacking mice with the transformed ES cells, the researchers detected new production of dystrophin in the muscles of the treated mice and observed improved muscle strength and coordination in the mice. 'The improved coordination is significant because it shows the ES cells have benefitted the animal's quality of life, not simply caused an isolated growth with no overall improvement' explained Dr Rita Perlingeiro, who led the team of researchers.

The success of the technique arose from two important advancements made by the team in producing the therapeutic ES cells. Firstly, they activated a genecalled Pax3 in the ES cells which triggered them to begin turning into new muscle cells. They then purified the partially-formed muscle cells, making sure they excluded all other ES cells which might otherwise form tumours when transplanted into the DMD mice. 'We know with ES cells you have to find a way to pull out the cells you want' said Dr Perlingeiro, adding 'even if there are ten undesirable cells, that's too many'. But after three months the treated mice were tumour-free, validating the efficacy of the team's cell-sorting method.

The positive outcome of these experiments offers hope that they may eventually be translated into new stem cell-based therapies for the currently incurable human muscular dystrophies. Dr Marita Pohlschmidt, director of research at the UK's Muscular Dystrophy Campaign, told the BBC: 'the results 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, she cautioned that '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'.

Dr Perlingeiro acknowledged that a human therapy was a long way in the future and that both exhaustive tests in mice and a greater understanding of human ES cell biology would be required before clinical trials could be considered. But she remains optimistic, saying 'you go brick by brick to build something'.