Stem Cells Graft In Spinal Cord, Restore Movement In Paralyzed Mice

The researchers introduced neural stem cells into the spinal fluid of mice and rats paralyzed by an animal virus that specifically attacks motor neurons. Normally, animals infected with Sindbis virus permanently lose the ability to move their limbs, as neurons leading from the spinal cord to muscles deteriorate. They drag legs and feet behind them.

Fifty percent of the stem-cell treated rodents, however, recovered the ability to place the soles of one or both of their hind feet on the ground.

"This research may lead most immediately to improved treatments for patients with paralyzing motor neuron diseases, such as amyotrophic lateral sclerosis (ALS) and another disorder, spinal motor atrophy (SMA)," says researcher Jeffrey Rothstein, M.D., Ph.D.

"Under the best research circumstances," he adds, "stem cells could be used in early clinical trials within two years."

"The study is significant because it’s one of the first examples where stem cells may restore function over a broad region of the central nervous system," says neurologist Douglas Kerr, M.D., Ph.D., who led the research team. "Most use of neural stem cells so far has been for focused problems such as stroke damage or Parkinson’s disease, which affect a small, specific area," Kerr explains.

In the rodent study, however, injected stem cells migrated to broadly damaged areas of the spinal cord. "Something about cell death is apparently a potent stimulus for stem cell migration," says Kerr. "Add these cells to a normal rat or mouse, and nothing migrates to the spinal cord."

In the study of 18 rodents, the researchers injected stem cells into the animals’ cerebrospinal fluid via a hollow needle at the base of the spinal cord — like a spinal tap in reverse. Within several weeks, the cells migrated to the ventral horn, a region of the spinal cord containing the bodies of motor nerve cells.

"After 8 weeks, we saw a definite functional improvement in half of the mice and rats," says Kerr. "From 5 to 7 percent of the stem cells that migrated to the spinal cord appeared to differentiate into nerve cells, " he says. "They expressed mature neuronal markers on their cell surfaces. Now we’re working to explain how such an apparently small number of nerve cells can make such a relatively large improvement in function.

"It could be that fewer nerve cells are needed for function than we suspect. The other explanation is that the stem cells themselves haven’t restored the nerve cell-to-muscle units required for movement but that, instead, they protect or stimulate the few undamaged nerve cells that still remain. We’re pursuing this question now in the lab."

The rodents infected with the Sindbis virus are a tested model for SMA, Kerr noted. SMA is the most common inherited neurological disorder and the most common inherited cause of infant death, affecting between 1 in 6,000 and 1 in 20,000 infants. In the disease, nerve cells leading from the spinal cord to muscles deteriorate. Children are born weak and have trouble swallowing, breathing and walking. Most die in infancy, though some live into young childhood.

With ALS, which affects as many as 20,000 in this country, motor nerves leading from the brain to the spinal cord as well as those from the cord to muscles deteriorate. The disease eventually creates whole-body paralysis and death.

The research was funded by grants from the Muscular Dystrophy Association and Project ALS.

Other scientists were Nicholas Maragakis, M.D., John D. Gearhart, Ph.D., of Hopkins, and Evan Snyder, at Harvard.

Related Web sites:

This site describes SMA in detail: http://www.andrewsbuddies.org/whatissma.html

This site deals with ALS research at Hopkins: http://www.neuro.jhmi.edu/alscenter/index.html