Oct. 2, 2008

Supercharged Stem Cells Aid ALS Rats

Scientists at the University of Wisconsin-Madison and institutions in the United Kingdom and Switzerland have shown that stem cells derived from human bone marrow and then engineered to produce a neuroprotective substance can significantly slow the course of a disease resembling human ALS (amyotrophic lateral sclerosis) in rats.

Masatoshi Suzuki and Clive Svendsen, both at the University of Wisconsin's Waisman Center, and colleagues, who published their findings online Sept. 16 in Molecular Therapy, say the stem cells acted as miniaturized, long-term "pumps" that delivered GDNF (glial-derived neurotrophic factor) to the rats after being injected into their muscles. The neuroprotective compound apparently traveled to nerve cells from the muscle tissue.

Rats with mutated SOD1 genes and a disease resembling human ALS that were treated with the supercharged stem cells lived as much as 28 days longer than their untreated counterparts. Even in rats with a very severe, rapidly progressive disease, caused by high numbers of mutated SOD1 genes, the average survival time was prolonged by 18 days.

The stem cells the researchers used, known as "mesenchymal" stem cells, normally give rise to bone, muscle, cartilage, tendons or fat cells. The investigators note that these stem cells, even without being supercharged to produce GDNF, secrete other proteins that may be neuroprotective, reduce inflammation and enhance blood-vessel formation.

In fact, the stem cells preserved significant numbers of motor neurons, the nerve cells that control muscle activity that are lost in ALS, even when they didn't produce GDNF. However, the benefit was greater when the cells were equipped with GDNF genes.

The researchers note that muscle is an accessible tissue compared to the nervous system and that delivering GDNF or other protective genes via stem cells has advantages over other gene therapy approaches.

For instance, they say, delivering therapeutic genes directly to the recipient's existing cells, which are already undergoing ALS-related degeneration, might not be as beneficial as delivering these genes via new cells that are healthy and bring additional advantages to the targeted areas.

"This was a combined therapy approach," Svendsen said. "Both the stem cells, and the GDNF they released, seemed to work together to provide these effects."