"Our work does lay an important and critical early foundation for techniques that we hope will restore function to nervous systems damaged by amyotrophic lateral sclerosis (ALS), spinal motor atrophy (SMA), and other degenerative motor neuron diseases," says Jeffrey Rothstein, M.D., Ph.D., professor of neurology and director of the Packard Center for ALS Research at Johns Hopkins, one source of funding for the work. "But there's a long way to go."
In preliminary test-tube studies, the researchers saw that their ES-derived motor neurons and healthy muscle cells "conversed," each pumping out -- within hours -- agents needed to pave the way for the cells' "hookup."
In the lab dishes, Kerr saw the new motor neurons grow outward toward the muscle cells and form proper connections with proper receptors. The muscle cells that were connected to nerve cells even began to contract in the laboratory dish.
To investigate whether the phenomenon would happen in animals, the team of scientists implanted the pre-motor neurons into the spinal cords of paralyzed adult rats, easing them into areas typically rich in motor neurons. "We transplanted roughly 12,000 cells per animal, and about 4,000 of them 'took,'" says Kerr. "They became true motor neurons and looked gorgeous."
In these first animal studies, however, the axons of these new neurons didn't poke through the spinal cord and out to muscle targets. Kerr reasoned that, because myelin is a potent inhibitor of axon growth, the myelin-coated neurons that ring the spinal cord were probably trapping the new motor neurons inside.
Fortunately, other scientists had recently uncovered molecules that can block myelin's axon-repelling effect. So the team implanted the rats with a pump to drip these myelin "de-squelchers" in the vicinity of the animals' spinal cords. As a result, some motor neurons extended themselves through the cord.