Researchers have found a way to sharply reduce the number of embryos required for an experimental treatment of Parkinson's disease. Treating fetal cells with an enzyme that prevents them from committing suicide may cut the need for fetuses by as much as 75%, they report in the latest issue of Nature Medicine.
Researchers have for years tried treating Parkinson's patients by injecting fetal cells into their brains, to replace cells dying as a result of the disease. The operation benefits some patients greatly and might someday become the standard therapy. But because 90% to 95% of the fetal cells die during the procedure, researchers need at least four donated fetuses to perform one operation, says Hakan Widner, a neurologist at Lund University in Sweden. Finding four women to donate aborted fetuses at almost the same time has proved nearly impossible, at least in Lund. "That has not happened once in the last 12 months here," he says.
The dying fetal cells appear to be following a suicide program, so Widner and his colleagues reasoned they might prolong the cells' longevity by inhibiting an enzyme called caspase, which touches off the cell's suicide cascade. They used a rat model of Parkinson's disease in which a lesion is made to a group of dopamine-sensitive neurons on one side of the brain. This causes the animal to circle continuously in one direction. They injected the brains of eight of these rats with fetal brain cells treated with Ac-YVAD-cmk, a caspase inhibitor molecule, and transplanted untreated fetal cells into eight other rats.
After 2 weeks, the rats with the pretreated cells had nearly stopped making their circles; the control group had improved only somewhat. After 6 weeks, the first group had begun turning in the opposite direction, indicating that an excess of the transplanted cells had survived and taken up their new function in that side of the brain. Biopsies showed that 4 times as many cells had survived in the pretreated transplants. If the caspase inhibitor treatment works in humans as well, says Widner, only one or two embryos per transplantation would be needed.
Caspase inhibitors may complement similar treatments now being tested in humans, such as pretreating the cells with growth factors, says Curt Freed, a neurologist at the University of Colorado Health Sciences Center in Denver. If both treatments are successful, they might be combined for even greater effect, he says.