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FOR RELEASE: November 8, 2000CONTACT: Tom Curtis, Public Affairs(409) 772-2455, (800) 228-1841, [email protected]

Professor Claire E. Hulsebosch(504) 523-5906 through Nov. 8(409) 772-2939 Nov. 9 and thereafter[email protected]

EMBARGOED FOR RELEASE UNTIL AFTER 2 P.M NOVEMBER 8, 2000.

Bio-engineered Cells Boost Mobility and Seem to Relieve Pain

In Animals with Spinal Court Injuries, UTMB Study Shows

NEW ORLEANS-In experimental animals with spinal cord injuries, cells bio-engineered to produce the neurotransmitter serotonin apparently can relieve chronic pain and clearly can increase mobility, researchers from the University of Texas Medical Branch at Galveston (UTMB) have found. The study was to be reported for the first time on Wednesday, Nov. 8, at the annual meeting of the Society for Neuroscience in New Orleans.

Approximately 11,000 new human spinal cord injuries occur annually in the U.S. and they result in a devastating loss of sensory and motor function below the point where the injury occurs. Once spinal shock has subsided, reflexes return and various kinds of pain develop. Estimates vary regarding how often pain occurs following spinal cord injury, but some range as high as 94 percent. This kind of pain is difficult to treat and often is extremely debilitating.

The researchers cautioned that their research results in lab animals are preliminary and learning precisely how they will apply to human beings will require many years of additional studies. Nonetheless, the scientists believe this first study may have important implications for the ultimate development of effective new therapies for people with spinal cord injuries.

The primary author of the new study was UTMB graduate student Bryan Hains. The senior author was his mentor, Claire Hulsebosch, professor of anatomy and neuroscience at UTMB. The cells were bio-engineered by another author of the study, Mary Eaton, assistant professor of neurological surgery with the Miami Project to Cure Paralysis at the University of Miami School of Medicine.

Huslebosch explained that when the bio-engineered cells were transplanted into the area of injury in rats, "these cells survived and secreted serotonin into the cerebrospinal fluid." She added, "More important, animals that received the transplanted cells demonstrated significantly improved recovery of locomotor function and statistically significant reduction in pain-related behaviors when compared to controls" - that is, compared to laboratory rats that didn't receive the bio-engineered, serotonin-producing cells.

Hulsebosch and her colleagues at UTMB developed what is known as a rodent "model" of spinal cord injury, which means using injuries in rats to mimic the loss of function and pain that occurs in human patients. The rats apparently experience sensations common to people with spinal-cord injuries in which normally non-painful stimuli cause pain and painful stimuli become more painful. These pain "syndromes, " Hulsebosch explained, are caused by lower-than-normal levels of the neurotransmitter serotonin, which in part helps to block pain sensations.

Using transplanted cells in human beings as a source of pain-reducing compounds such as serotonin could be a major advance in pain management, the UTMB group believes. Hains explained that the cells act as biological mini-pumps, providing a continuous and renewable source of compounds directly to the site where pain originates. Also, he said, because very low doses of compounds are secreted by the cells into a very small area without exposing other organ systems or tissues, this approach could minimize or even prevent the development of drug tolerance and the need for dose increases over time. The bio-engineered cells used in his experiment were immortalized, Hains noted, meaning that unlike normal cells, they do not die after a fixed number of generations; but unlike many other immortalized cells, he added, these immortalized cells do not create cancerous tumors.

Several questions remain to be answered, the scientists noted, including whether anti-rejection drugs are required to keep the body's immune system from attacking the transplanted cells, whether the procedure is applicable to other spinal cord injuries, and whether transplanting such cells immediately following injury would be helpful. The team also is examining transplant-induced changes in the spinal cord and transplanted tissue and how these alterations in spinal cord circuitry might affect behavior.

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