US researchers have used human stem cells to lessen the symptoms of motor neurone disease in rats bred to have symptoms of the condition. The scientists, based at Johns Hopkins University, Baltimore, showed that injecting fetal nerve stem cells into the spines of rats with amytrophic lateral sclerosis (ALS) delays nerve damage and slightly prolongs the life of the animals. Team leader Vassilis Koliatsos says the study, published in the journal Transplantation, offers 'proof of principle' for using stem cell transplants to treat the disease.
ALS, also known as Lou Gehrig's disease, is a progressive, incurable paralysis caused by gradual damage to motor neurons - nerve cells in the brain and spine. As the nerves gradually waste away, people with the condition eventually lose all control over their voluntary movements. The causes of motor neurone disease remain largely unknown, although ten per cent of cases are linked to an altered gene, called SOD-1. In the latest study, the researchers used genetically altered rats that have a mutated human SOD-1 gene, which means they develop symptoms of ALS.
The scientists injected fetal nerve stem cells into the lower spine of presymptomatic rats, and dead stem cells in the spines of control animals. Both groups of rats were then weighed and tested for strength twice a week for 15 weeks. According to Koliatsos, weight loss indicates the onset of the disease, while measuring strength shows how quickly it is progressing. The scientists determined how strong the rats were by coaxing them to crawl up an angled plank, and measuring the angle at which they could no longer cling on for more than five seconds.
The team found that the treated animals started losing weight at 59 days and lived for 86 days after the injection, while the control group started losing weight at 52 days and lived for 75 days. Microscopic examination of the transplanted cells revealed that more than 70 per cent of them developed into nerve cells, and many formed new connections to other cells in the rats' spinal cords. The transplanted cells also made proteins specific to nerve cells, such as a growth factor called GNDF.
Koliastsos cautions that although clinical applications are still 'far from possible', the fact that the cell transplants formed new nerve cells in the spinal cord was 'a pleasant surprise'. 'We were extremely surprised to see that the grafted stem cells were not negatively affected by the degenerating cells around them, as many feared introducing healthy cells into a diseased environment would only kill them', he said.
The team now plans to carry out further experiments in which stem cells will be injected along the full length of the spine, so that nerves and muscles above the waist - especially those involved in breathing - also benefit. They hope this will further increase the lifespan of the affected animals.
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