Extension of Life in ALS-affected Rats Possible by Increasing Number of Good Neurons

Experiments conducted on rat models of ALS, also called Lou Gehrig's disease, have shown that transplanting a new line of stem cell-like cells reduces neuron loss, and extends life, Johns Hopkins researchers have revealed.

Dr. Nicholas Maragakis, an associate professor of neurology at Johns Hopkins who led the research team, says that the new work supports the hypothesis that artificially outnumbering unhealthy cells with healthy ones in targeted parts of the spinal cord preserves limb strength and breathing and can increase survival.

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The study suggested parts of the cervical spinal cord that control the diaphragm muscles, which are largely responsible for breathing, might reap the most benefit from such a therapy. That was so because 47 percent more motor neurons survived there than in untreated model animals.

Respiratory failure from diaphragm weakness is the usual cause of death in ALS.

"While the added cells, in the long run, didn't save all of the nerves to the diaphragm, they did maintain its nerve's ability to function and stave off death significantly longer," Nature Neuroscience quoted Maragakis as saying.

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"We intentionally targeted the motor neurons in this region since we knew that, as in ALS, their death results in respiratory decline," he added.

The study also suggested that the transplanted cells, called glial restricted precursors (GRPs), could address a well-known flaw in people with ALS and in its animal models - stunted ability to clear away the neurotransmitter glutamate.

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Excess glutamate overstimulates the motor neurons that spark muscle movement, causing death. The event, called excitotoxicity, also occurs in other neurological diseases.

According to the researchers, their study adds gives more strength to the proposition that finding more effective ways to avoid or lessen excitotoxicity, a major bad guy in ALS, could help protect the nervous system.

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During the study, the researchers had transplanted about 900,000 glial restricted precursors overall to specific sites in the cervical spinal cord of each model rat in early stages of disease.

They were amazed to find that none of the GRPs damaged the spinal cord or formed tumours, a worry with some stem cell therapies.

"This targeted cell delivery to the cervical spinal cord is a promising strategy to slow that loss of motor neurons in ALS. We hope at some point that these principles will translate to the clinic," said Maragakis.

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