Oct. 14, 2008

Donated Bone-Marrow Stem Cells Reach Target, Don't Slow ALS

Six men with ALS (amyotrophic lateral sclerosis) who received intravenous infusions (transplantations) of donated bone- marrow stem cells failed to derive any apparent benefit from the cells, although the study showed that such cells can enter the central nervous system from the bloodstream. The ability of cells from donors to penetrate barriers surrounding the brain and spinal cord supports their potential use as carriers of therapeutic substances.

MDA grantee Stanley Appel at Methodist Neurological Institute in Houston coordinated the study team, which published its results in the Oct. 14 issue of Neurology.

"Our study showed no clinical benefit for ALS patients, which should send a warning not to believe the exaggerated claims for stem-cell transplantation in ALS at the present time," Appel said.

Six men with sporadic (nonfamilial) ALS, ranging in age from 35 to 59, underwent radiation treatment to partially destroy their own bone marrow, followed by medications to suppress their immune systems and help them accept bone- marrow stem cells donated by siblings.

All study participants accepted the donated cells, with four of the six eventually showing 100 percent donated cells in their bloodstreams.

Three patients had rapid progression of their ALS following transplantation, with no evidence of clinical benefit.

A fourth experienced slow loss of function and required invasive (tracheostomy-delivered) respiratory support about three years later

Another experienced slow disease progression for the first 14 months after transplantation and then rapid disease progression.

Only one patient's ALS progressed at an overall rate that was slower than average for this disease, living for 7.5 years after symptom onset. The investigators say his age (35 at study enrollment), rather than the bone-marrow transplant, was the likely cause of his slow disease progression.

In three study participants, the brain and spinal cord were examined after death.

Two patients who had shown 100 percent donor cells in their blood showed 16 percent to 38 percent donor DNA at sites of ALS injury in the spinal cord. Both also showed donor DNA in the parts of the brain that their symptoms indicated were the most affected by the disease.

In the third patient, whose blood had carried only a small percentage of donor cells, there was no donor DNA in the spinal cord or brain.

The donated cells showed a marked preference for sites of injury, areas to which molecular "damage signals" probably attract them.

"This first long-term study of bone-marrow stem cell transplantation in ALS in humans is important," Appel said, "in that it showed us that donated cells can get into the brain and spinal cord and home to the sites of injury specifically.

"Although stem cells by themselves didn't provide any benefit to the patients, further studies in which stem cells serve as delivery vehicles for therapeutic genes or proteins may prove of value, especially since donor cells appear to enter areas of the nervous system at sites of ALS injury.

"Risky injections of donor cells containing therapeutic compounds directly into an ALS patient’s spinal cord would probably not be required. Instead, delivering potentially therapeutic compounds via bone-marrow stem cells could probably be accomplished with infusions into the bloodstream."