October 30, 1998

Cancer drug may impact spinal cord injuries: study

Cancer drug may impact spinal cord injuries: study

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Dr. Carl Hellerqvist (right), and Drs. Artur Wamil and Barbara Wamil are testing CM-101's ability to aid in treating spinal cord injuries. (Photo by Donna Jones Bailey)

Mice paralyzed with spinal cord injuries recovered walking ability after treatment with a compound discovered and initially developed as an anti-cancer drug at Vanderbilt University Medical Center, VUMC researchers report this week.

The work with bacterial toxin CM-101 was reported in the Oct. 27 issue of the Proceedings of the National Academy of Sciences. The drug works by blocking a "pathoangiogenic" process that creates new blood vessels in an inflammatory response to injury or to support the growth and spread of tumors, the researchers say.

"The key to preventing serious damage in spinal cord injury appears to be blocking the inflammatory process, which is the body's effort to clean up the damaged tissue but which becomes self-destructive," said Dr. Carl G. Hellerqvist, associate professor of Biochemistry and Medicine and senior author of the PNAS article. "If you do that, the body has a tremendous ability to recover. CM-101 can block that inflammatory process that leads to excessive tissue damage."

Co-authors of the article are Dr. Artur W. Wamil, research assistant professor of Anesthesiology, and Dr. Barbara D. Wamil, research assistant professor of Biochemistry.

Spinal cord injury is often devastating and affects an estimated 10,000 people in the United States each year, according to the Spinal Cord Injury Information Network based at the University of Alabama-Birmingham. As many as 200,000 Americans — most between ages 16 and 30 — are alive today with SCI, which is most often caused by motor vehicle crashes, acts of violence, falls and sports injuries.

CM-101 was initially discovered during the study of group-B streptococcus infection in infants. CM-101 is a toxin produced by the bacteria that attacks newly formed blood vessels in the lungs and causes deadly lung disease in infected infants. Hellerqvist's colleagues in the discovery of CM-101 were Dr. Mildred Stahlman and Dr. Hakan W. Sundell, professors of Pediatrics, and Dr. Jorge Rojas, associate clinical professor of Pediatrics.

Because tumors prompt development of blood vessels to support their growth and spread, Hellerqvist's group began investigating CM-101 as a potential anti-cancer drug. It has shown promise in the laboratory and in early patient studies, which are ongoing.

Because pathoangiogenesis is also involved in wound healing, joint damage from rheumatoid arthritis and spinal cord injury, the researchers began investigating CM-101's potential implications in these areas as well.

In work reported in PNAS, Hellerqvist and his colleagues report the results of a randomized study in which mice were paralyzed with a spinal cord crush injury. Some of the mice were then treated with CM-101.

The scientists treated 26 mice with CM-101 delivered intravenously one hour after injury and repeated every other day for five more infusions. Of this group, 25 survived 28 days after the injury, and 24 of them recovered the ability to walk within two to 12 days.

In the control group, six of the 14 untreated mice survived 24 hours after the injury, and none recovered function of their paralyzed legs, the researchers report.

Both groups of animals were analyzed by magnetic resonance imaging, which found reduced damage at the site of the crushing injury in the treated mice. This finding was corroborated by microscopic examination of spinal cord sections of treated and control animals.

Electrophysiologic measurements on isolated spinal cord tissue and cells in culture suggested that CM-101 may restore connectivity of nerve cells not only by reducing scarring but by protecting damaged nerve cells from degeneration and death, they report.

"CM-101 appears to be more than anti-pathoangiogenic; it also may have protective properties," Hellerqvist said.