Cancer drug helps paralyzed mice walk.

A bacterial toxin that can destroy the developing lungs of a newborn child has unexpectedly enabled mice paralyzed by spinal cord injuries to walk again.

The toxin, known as CM101, was originally considered as a cancer drug by a research group led by Carl G. Hellerqvist of Vanderbilt University in Nashville. Bacteria known as group B streptococci secrete this carbohydrate molecule, which binds to a cell-surface protein found on blood vessels in newborn infants' lungs, marking them for destruction by an immune response. Since growing tumors depend upon the formation of new blood vessels, which also bind the toxin, Hellerqvist and his colleagues are testing whether CM101 can similarly mark tumors for destruction.

Recently, the researchers started to wonder about spinal cord injuries. They noted that the scar that often forms at the site of such an injury may be a major impediment to the cord's recovery. Since this scarring depends on immune cells delivered by new blood vessels, they hypothesized that CM101 might have a therapeutic effect.

When given intravenously within several hours of a paralyzing spinal cord injury and for several days after, CM101 allowed 24 out of 26 mice to regain the ability to walk within 2 to 12 days, the scientists report in the Oct. 27 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES. In contrast, none of 14 untreated mice suffering a similar injury recovered their mobility, and 8 died within 24 hours.

CarboMed, a firm founded in 1990 by Hellerqvist to commercialize CM101, is encouraged by both the new results and recent cancer trials that indicate the drug is safe. The company plans to test the compound on people immediately after they have suffered spinal cord injuries. "By the end of next year, we should be in clinical trials," says Hellerqvist.

While several investigators who study spinal cord injuries say that such a leap is premature until CM101 undergoes significantly more animal testing, some of them are nevertheless impressed by the apparent recovery of the mice. "The results are phenomenal," says Arlene Y. Chiu of the National Institute of Neurological Disorders and Stroke in Bethesda, Md., who recently heard Hellerqvist present his results and saw a video of the treated mice walking and climbing.

Chiu and other investigators caution that Hellerqvist's group didn't use an established model of spinal cord injury but developed its own method of damaging the cord, complicating comparisons with other treatments. Moreover, the large percentage of deaths in the untreated group is unusual for spinal cord injuries and makes evaluating CM101 a challenge, says Naomi Kleitman of the Miami Project to Cure Paralysis.

Further research is needed to explain how CM101 works. Some evidence collected by Hellerqvist suggests that it indeed eliminates scarring and so encourages new connections among cells. Other experiments suggest that CM101 may protect cells whose connections remained intact. "The drug appears to preserve the overall health and structure of the nerve cells," Kleitman says.