July 31, 2008

Scientists Create Nerve Cells From
ALS Patient's Skin Cells

MDA-supported scientists at Harvard University in Cambridge, Mass., and Columbia University in New York have created muscle-controlling nerve cells known as motor neurons from the skin cells of a patient with ALS (amyotrophic lateral sclerosis, or Lou Gehrig’s disease).

MDA-supported Hiroshi Mitsumoto, who directs the Eleanor and Lou Gehrig MDA/ALS Center at Columbia, was part of the study team.

John Dimos of the Harvard Stem Cell Institute and colleagues published their findings today in Science Express, an online service of the journal Science.

ALS is a degenerative disease of the motor neurons, characterized by progressive paralysis. Patients usually die within three to five years of diagnosis. It’s familial about 10 percent of the time, but identifying its cause in the remaining 90 percent of cases has so far remained elusive.

“Much of the hope invested in patient-specific stem cells is based on the assumption that it will be possible to differentiate [mature] them into disease-relevant cell types,” the study authors say, referring to the process of coaxing a stem cell down a particular developmental path, such as that of a nerve cell.

One goal of such differentiation is the possibility of using such cells to replace the patient’s own, disease-affected cells. Since the replacement cells would come from the patient, the immune system would likely accept them.

Another goal is to study the way in which specific cell types from a disease-affected patient develop, which should provide important insights into the disease process.

“This research opens new avenues in the search for the exact cause of ALS and details of the disease process, and increases our ability to test new therapies,” said Sharon Hesterlee, MDA’s vice president of Translational Research. “We were pleased to help support this work.”

The study team collected skin cells from an 82-year-old woman with a familial form of ALS and then “turned back the clock” in these cells, inducing them to become like the cells of embryos, but without the capability of actually forming embryos. After the cells were reprogrammed back to an embryo-like state, the researchers coaxed them to develop into motor neurons.

Other research teams have recently created similar “induced pluripotent stem cells,” but until now, it wasn’t clear that the process could be accomplished in cells from elderly patients with chronic diseases.

“Our study demonstrates the feasibility of producing large numbers of motor neurons with a patient’s exact genotype [genes], which would be immune-matched to that individual, a long sought-after goal of regenerative medicine,” the study’s authors write. “However, several major challenges must be resolved before cell replacement therapy using iPs [induced pluripotent stem cell] technology can become a clinical reality.”

Among these challenges, they say, are ensuring the safety of iPS cells for transplantation into patients, since the current methods used for reprogramming could cause malignancies; and correcting defects, such as genetic errors, that caused the disease in the first place.

Replacing damaged motor neurons involves the additional hurdle of ensuring that the cells go to the right place in the brain or spinal cord and connect to muscle fibers and other nerve cells properly.

To circumvent this significant obstacle, some experts advocate the creation of nervous-system support cells called glia from iPS cells and using those, instead of motor neurons, for transplantation.

Glia don’t have to localize to a specific place, and studies in rodents with an ALS-like disease have shown that having healthy glia mitigates disease severity. The Harvard and Columbia researchers say they’ve also created cells they believe are glia.