Pumping Out Hope: Stem cells secrete brain-preserving protein

Because stem cells can grow into many different cell types, researchers have touted them for replacing cells damaged by injury or disease (SN: 4/2/05, p. 218: Full Stem Ahead). However, some scientists also envision the cells as pumps for delivering drugs. New research suggests that such living drug pumps could eventually treat Parkinson’s disease, a progressive neurological disorder with no known cure.

Parkinson’s disease occurs when brain cells that produce dopamine malfunction and die. Studies have shown that repeated doses of a protein called glial-cell line–derived neurotrophic factor (GDNF) can protect dopamine-producing cells in lab cultures.

Injections of GDNF into the bloodstream aren’t practical because the protein can’t traverse the blood-brain barrier, a feature of the circulatory system that shields the brain from many chemicals.

In ongoing trials, researchers have implanted mechanical GDNF pumps in Parkinson’s patients’ skulls. However, notes neuroscientist Allison Ebert of the University of Wisconsin–Madison, the mechanical-pump method is expensive and requires upkeep, including monthly GDNF refills.

Seeking a new method to transport GDNF to dopamine-making cells, Ebert and her colleagues, led by

Wisconsin–Madison neuroscientist Clive Svendsen, slipped extra copies of the gene for GDNF into stem cells that normally make insignificant amounts of the protein. These neural-progenitor cells can morph into several kinds of brain cells.

After testing the stem cells to make sure they produced substantial amounts of GDNF in the lab, the researchers injected them into the brains of rats that had been treated with a slow-acting drug that selectively kills dopamine-producing cells. In a different group of rats treated with the same toxic drug, the researchers injected normal neural-precursor cells that didn’t make significant GDNF.

After 2 weeks, Svendsen’s team compared the brains of rats in the two groups. Although the new cells seemed to integrate well into the brain tissue of both groups of rodents, the researchers found that those rats with the cells producing abundant GDNF had about 20 percent more surviving dopamine-making cells than the other rats did. These effects persisted when the researchers compared the rats’ brains 9 weeks later. Svendsen and his colleagues report their results in an upcoming Gene Therapy.

The new study is a “good, important, first step in trying to think about using this approach for Parkinson’s disease,” says Evan Snyder of the Burnham Institute for Medical Research in La Jolla, Calif., who has used a similar method to turn stem cells into pumps for drugs used to treat other neurological diseases and cancer.

However, notes neurobiologist Don M. Gash of the University of Kentucky in Lexington, the new findings are “good science, but a long way from being good medicine.” Gash points out that the amount of GDNF released by Svendsen’s stem cells can’t currently be regulated, whereas that in artificial pumps can. Either over- or under-production of dopamine by the cells could eventually lead to adverse effects.

Ebert says that she and other members of Svendsen’s team plan to tackle this challenge in future studies.