Blocking immune response to spinal cord injury can improve chances for recovery

November 13, 2003

Irvine, Calif., Nov. 13, 2003 -- People who suffer spinal cord injuries may have a greater chance of recovery if treated with drugs that block the body's own immune response to the initial trauma, researchers from the Reeve-Irvine Research Center at UC Irvine have found. In addition, UCI neurologist Hans Keirstead and immunologist Thomas Lane have laid the foundation for these drugs by creating antibodies that, when tested on rats, stopped the secondary nerve and spinal cord damage caused by the immune system response. Use of these antibodies resulted in significantly improved rates of recovery.

Previous studies have shown that the body's immediate immune system response to a spinal cord injury actually worsens the condition. Results of this UCI study appear in the November issue of Experimental Neurology.

"While the primary tissue damage caused by the initial spinal trauma cannot be reversed, we've discovered that the secondary damage caused by immune responses can be prevented, which gives those who suffer these injuries hope for recovery," Keirstead said.

Immediately after spinal cord trauma, cells called chemokines are released at the injury site and induce inflammation. One specific chemokine called CXCL-10 recruits immune system cells called T-lymphocytes. Normally, T-cells battle disease and other invading agents in the body, but in the central nervous system during spinal injury and periods of disease in multiple sclerosis, these T-cells create toxic compounds that attack and damage spinal tissue and nerve fibers.

In tests on rats with induced spinal cord injuries, Keirstead and Lane treated one group with their antibody drugs that blocked CXCL-10 cells from recruiting T-cells to the injury site. Another group received no therapies. In the group treated with the antibodies, the researchers found a significant reduction in T-cell counts and spinal damage. The untreated rats showed increased T-cell levels and greater secondary tissue damage.

In further tests 14 days after the initial injury, Keirstead and Lane found that the treated rats had far greater mobility than the untreated mice, suggesting that further tissue damage caused by T-cells can lead to increased paralysis.

"The difference in mobility between the treated and untreated rats was dramatic," Keirstead said. "It points to the necessity of treating people with antibodies immediately after their spinal cord injuries as part of both regular trauma care and their recovery program." Rafael Gonzalez, Janette Glaser and Michael T. Liu of UCI assisted on the study, which was supported by the Roman Reed Spinal Cord Injury Research Fund of California, Research for the Cures and individual donations to the Reeve-Irvine Research Center.

The Reeve-Irvine Research Center was established to study how injuries and diseases traumatize the spinal cord and result in paralysis or other loss of neurologic function, with the goal of finding cures. It also facilitates the coordination and cooperation of scientists around the world seeking cures for paraplegia, quadriplegia and other diseases impacting neurological function. Named for actor Christopher Reeve, the center is part of the UCI College of Medicine.

Keirstead and Lane also are principals in Ability Biomedical Corp., a pharmaceutical development firm developing chemokine-based therapeutic drugs for treating spinal cord injury and multiple sclerosis. They recently created a human antibody based on the one used in this study to be used in future clinical trials. In 2001, the researchers found that the same antibodies used in this study were also effective in stopping and reversing nerve damage in multiple sclerosis triggered by T-cells.

The University of California, Irvine is a top-ranked public university dedicated to the principles of research, scholarship and community. Founded in 1965, UCI is among the fastest-growing University of California campuses, with more than 24,000 undergraduate and graduate students and about 1,300 faculty members. The third-largest employer in dynamic Orange County, UCI contributes an annual economic impact of $3 billion.
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