Stem Cells Might Help in ALS and SMA in Unexpected Way

A study out today establishes that human stem cells can partly reverse a paralyzing neurological disease in rats — apparently without producing new nerve cells.

The research, which generated headlines when it began several years ago, offers hope that stem cell therapy will work against paralyzing human diseases like amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA).

A team led by Jeffrey Rothstein, co-director of the Muscular Dystrophy Association’s ALS Center at Johns Hopkins University in Baltimore, first reported the experiments at a scientific conference in 2000. Then, it was believed that stem cells — master cells that build tissues such as nerve and muscle — might replace cells lost to disease, but it now appears they’re better at repairing damaged cells.

Rothstein and his group injected human primordial germ cells (which can morph into any cell in the body) into the spinal cords of rats infected with Sindbis virus. The virus is harmless to humans, but kills motor neurons (muscle-controlling nerve cells) connected to the rats’ hind limb muscles.

After 12 weeks, the treated rats had recovered some movement, and their hind limbs were 40 percent stronger compared to those of rats that had received “sham” injections without stem cells.

Examining the rats’ spinal cords, the researchers found that many of the injected cells had taken up residence there, but surprisingly few of the cells had become motor neurons. Further experiments showed that the stem cells release transforming growth factor-alpha (TGF-alpha) and brain-derived neurotrophic factor (BDNF) -- proteins that enhance neuronal survival and growth — and that blocking these proteins eliminated the stem cells’ beneficial effects.

The research appears in the current issue of the Journal of Neuroscience.

“In some ways our results reduce stem cells to the nonglamorous role of protein factories, but the cells still do some amazing, glamorous things we can’t explain,” said Hopkins researcher Douglas Kerr, in a statement issued by the university.

Human trials of stem cell therapy for ALS and SMA, which destroy motor neurons on a devastating scale, are still years away, the group says. But in preparation, they’ve begun testing stem cells in monkeys with motor neuron disease, and they’ve engineered rats with mutations in SOD1, a gene linked to about 2 percent of ALS cases. Click here and here for more information.