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Oct 20, 2008

Outnumbering Unhealthy Cells with Healthy Ones Helps Sustain Breathing in ALS Mice

  • Scientists say that transplanting a new line of stem cell like cells into rat models shifts key signs of neurodegenerative disease in general and those of amyotrophic lateral sclerosis (ALS) in particular. They found that it slowed the animals' neuron loss and preserved limb strength and breathing, basically  extending life.

    Investigators found that it is most beneficial to inject the glial restricted precursors (GRPs) into parts of the cervical spinal cord that control the diaphragm muscles largely responsible for breathing. In ALS patients, the death of motor neurons in this region is known to lead to respiratory decline.

    The researchers observed that 47% more motor neurons survived there than in untreated model animals. “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,” says neuroscientist Nicholas Maragakis, M.D., an associate professor of neurology at Johns Hopkins who led the research team.

    The GRPs also cleared away the neurotransmitter glutamate, which is usually difficult to remove in people with ALS. The resultant excess glutamate overstimulates the motor neurons that spark muscle movement, causing death.

    The researchers transplanted 900,000 GRPs to specific sites in the cervical spinal cord of each model rat in early stages of disease. These GRPs began life as astrocyte progenitor cells from healthy rat spinal cord tissue. Following transplant, they transformed into mature, healthy astrocytes, found living alongside sick motor neurons, the scientists note. The astrocytes maintained proper ion levels and nutrient support of nerve cells.

    At least a third of the added GRPs functioned after their transplantation. With time, almost 90% of the GRPs had differentiated into astrocytes. Unlike the model rats' own astrocytes, the new ones continued to appear healthy. None of the GRPs damaged the spinal cord or formed tumors. Additionally, transplanting alternate GRPs - those that the team engineered to lack glutamate transporters - offered none of the protective properties.\

    The team consisted of researchers from Johns Hopkins and Invitrogen. The article appears online this week in Nature Neuroscience.

     



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