New Stem Cell Treatment Shows 'unambiguous' Benefits

Stem cell therapy has received a major boost from tests of an experimental treatment for an inherited muscle-wasting disease.

The study involved injecting the stem cells into golden retriever dogs with a condition that closely mimics Duchenne muscular dystrophy (DMD). The cells integrated into damaged muscle tissue and, in some cases, led to impressive improvements in the animals' walking ability.

"This is the most dramatic example that stem cells really have a lot of potential to regenerate damaged or diseased tissues," said Jeffrey Chamberlain at the Institute for Stem Cell and Regenerative Medicine in the University of Washington. He was not involved in the work. "There's been a lot of interest in applying stem cells to treating diseases, but so far that's been mainly theoretical. There haven't been any good examples of the success of that strategy."

Scientists believe that stem cells hold great promise in medicine because they are able become a variety of other cells and so could be used to rebuild damaged tissue.

Even sceptics who feel their potential has been over-hyped are impressed by the dog study. "I've actually been a bit of a cynic about the stem cell field, because I felt that it was initially over-sold," said Professor Dominic Wells, an expert in DMD at Imperial College, London, who did not contribute to the study.

"But when you start to see ... a clear and unambiguous contribution, then you start to believe there really is something in this technology." Except in rare cases, DMD affects only boys. It is one of the most common inherited diseases, though it is still rare on a national scale, with around 1,500 sufferers in the UK. As patients get older, their muscles gradually break down, leaving them increasingly weakened. By 11 years old, most patients are in a wheelchair and the majority do not live beyond their early 20s.

"Life expectancy has gone up a lot with this disease [because of new treatments], but what hasn't changed is the relentless muscle wasting," said Prof. Wells, "So the quality of life that this sort of treatment might offer is perhaps more important or as important as the longevity aspect."

The study, published today in Nature, tested two approaches to introducing associated stem cells with a working copy of the dystrophin gene - the one that is damaged in DMD patients - into dogs' blood vessels.

The team, led by Giulio Cossu at San Raffaele Scientific Institute in Milan, used cells from healthy 15-day-old puppies in six animals; another four dogs had some of their own cells removed, genetically repaired and re-injected - a form of gene therapy.

If the first approach were transferred to humans, it would probably mean using cells from the muscle of a living donor. Since these cells would be recognised as foreign by the patient's immune system and attacked, the recipient would have to take immune-suppressant drugs for the rest of their life. These drugs lead to an increased risk of certain cancers and other conditions, so to minimise the problem, doctors would probably opt to use a donor who was a close genetic match, such as a sibling or parent. The idea of using the patient's own cells, already fixed by gene therapy, is much more attractive because it avoids the rejection problem.

Prof. Wells said it would have been impossible to bring the treatment this far without trying it out on animals. An earlier version was tested in mice in 2003. "It is difficult to envisage any way that you could assess the potential of these cells outside of an animal," he said.

"The proof they actually are useful can only be done either in an animal or man and you are not going to get permission to put in a novel treatment that you have no evidence for works in people." Safety trials in human volunteers are already being planned.

There are a handful of treatment approaches already being tested for DMD. For example, one involves injecting short so-called "anti-sense" strands of DNA which change the way the faulty gene is expressed in the body and so restore it to normality. Another is to try gene therapy on the muscle cells in the body, using a benign virus to inject DNA into them.

Prof. Wells thinks that the different treatments might end up complementing each other. "There's a whole series of things going through at the moment. What we in the community think is that none of them will be perfect, but they may be additive."