Stem Cells Shed Light on ALS Cure

Researchers from Harvard and Columbia have moved one step closer to discovering the cause of the fatal neurodegenerative Lou Gehrig’s disease through a novel use of embryonic stem cells from mice.

Supporters of embryonic stem cell research have long pointed to the potential to use these cells to directly treat diseases of the nervous system. But the Harvard and Columbia teams assert that stem cells have a broader application in providing critical information for understanding many other human diseases.

The researchers have harnessed stem cells from mice embryos, which can develop into any kind of tissue, to create mutant nerve cells for studying the early stages of disease.

“With this strategy, it would be possible to study virtually any human disease,” said Harvard researcher Thomas P. Maniatis, who was a member of the Harvard team.

The scientists announced yesterday that they have discovered that a toxic molecule produced by non-neuron support cells causes the patterns of nerve cell death found in sufferers of Lou Gehrig’s disease, also known as Amyotrophic Lateral Sclerosis.

A significant amount of previous research into nerve diseases such as Lou Gehrig’s has focused primarily on neurons as a source of disease, but the researchers cite their results as proof that non-neuron cells merit serious investigation.

“Can you imagine what would be the fate of an individual that grew up in a bad neighborhood?” said Columbia researcher Serge Przedborski, drawing a parallel between crime-ridden areas and cellular environments. “What we found was that in fact, those normal motor neurons were dying due to the aspect of being surrounded by these mutant [support cells].”

Though the identity of the toxin produced by these cells is still a mystery, the researchers are optimistic about the prospects of discovering it and finding drugs to combat it.

“You’re looking at anywhere between three and four years,” Przedborski said.

Lou Gehrig’s disease is a currently incurable nervous system disease that strikes most sufferers in their 50s. The average victim lives only three to five years after diagnosis, according to Maniatis.

Though the studies used embryonic stem cells from mice, the researchers eventually plan to make the controversial move to human cells.

“This is our first demonstration that it’s not only viable but a very valuable approach. We’re hopeful that we’ll be able to exactly extrapolate this system with human embryonic stem cells,” said Harvard researcher Kevin C. Eggan, the project’s principal investigator.

Opponents of human embryonic stem cell research criticize studies such as those envisioned by the Harvard and Columbia teams for leading to the destruction of embryos that could develop into human beings.

Last year, President George W. Bush vetoed legislation loosening restrictions on federal funding for embryonic stem cell research. It was the first and only veto of Bush’s presidency. One month earlier, then-Governor of Massachusetts Mitt Romney made moves to restrict funding for embryonic research in the state, but current Governor Deval L. Patrick ’78 announced last month that he intends to reverse these funding limitations.

A significant portion of Harvard’s stem cell research is privately funded.

Many critics of using embryonic stem cells point to adult stem cells as a viable alternative for research, but for neurodegenerative diseases, the scientists at Harvard and Columbia disagree.

“No one has been able to differentiate those cells into motor neurons,” Eggan said. “For some reason, the adult stem cells that you can isolate in the spinal cord have lost their ability to do that. You have to have a more embryonic source.”

—Staff writer Clifford M. Marks can be reached at cmarks@fas.harvard.edu.