New stem cell findings point to future therapies for spinal musclar atrophy

Clive Svendsen

In the past few years, stem cell researchers have been taking advantage of the ability to create embryonic-like stem cells from skin to develop laboratory models of disease. The idea is simple: first, take skin from someone with a genetic disease (the skin cells will have the same genetic mutation as the cells effected in the disease). Next, turn those skin cells into embryonic-like stem cells called iPS cells. Then mature those stem cells into the type of cell that goes awry in the disease.

So far, researchers have followed this procedure to create cells in the lab dish with symptoms of Parkinson’s disease, autism, schizophrenia, Alzheimer’s disease, ALS and others. Researchers at Cedars-Sinai used the technique to create a laboratory model of the fatal childhood disorder spinal muscular atrophy, or SMA, back in 2009. Now, in work published in the June 19 online issue of PLoS ONE they have created more lab models of SMA but with newer techniques that are less likely to cause unwanted changes in the cells.

The point of all this work is to figure out what goes wrong in the disease, and to find drugs to fix the problem. Since all of these diseases occur in living neurons, which in general people are loath to part with, scientists have never had a way of studying how the disease forms in the lab. And if you don’t know what goes wrong in the first place, how can you fix it?

The latest in these disease-in-a-dish models comes from CIRM grantees led by Clive Svendsen who created motor neurons from the skin of two people with SMA. In the roughly 100,000 newborns born with the disease each year, the motor neurons that control muscle movement don’t form properly and the children are generally paralyzed by age three.

Svendsen and his group found that in the lab dish, the SMA stem cells didn’t form as many motor neurons as iPS cells from people without the disease. What they noticed is that the cells seemed to be dying off through a regulated process of cell death known as apoptosis. When they exposed the neurons to molecules that block apoptosis, the neurons lived.

A press release from Cedars-Sinai quotes Svendsen, who is director of their Regenerative Medicine Institute.

“With this new understanding of how motor neurons die in spinal muscular atrophy patients, we are an important step closer to identifying drugs that may reverse or prevent that process.”

The goal now is to start testing drugs on these SMA neurons to find ones that seem to reverse the disease. Those drugs could then become possible therapies for people with SMA.

CIRM funds $15 million in awards that could one day benefit people with SMA. You can see the complete list of those awards here.

A.A.