New Therapy Boosts Function in Paralyzed Rats

The findings were reported in the June 2004 issue of Nature Medicine.

Past studies have found that supporting cells from nerves outside the brain and spinal cord, called Schwann cells, can be used to make a bridge across the damaged spinal cord that encourages nerve fibers to regrow. Other research has suggested that cAMP (cyclic adenosine monophosphate) can turn on growth factor genes in nerve cells, stimulating the brain and helping to overcome signals that inhibit regeneration.

The current study is the first to try combining both approaches in an animal model of spinal cord injury. Researchers at the University of Miami School of Medicine (FL, USA) found that spinal cord injury triggers a loss of cAMP in the spinal cord and some parts of the brain. They transplanted Schwann cells into the spinal cords of rats in a way that bridged the damaged area. They also gave the rats a form of cAMP and a drug called rolipram, which prevents cAMP from being broken down.

This triple-combination therapy not only preserved but even elevated cAMP levels in nerve cells after injury and preserved many of the myelinated nerve fibers. The treated rats grew back many more nerve fibers than untreated rats or rats that received only one or two of the therapies. The regenerated fibers included many that carry serotonin, important for locomotion. Rats receiving the triple therapy had much better locomotion and coordination eight weeks after treatment than control rats.

"The behavioral improvements in the rats receiving the triple therapy are dramatically better than those reported previously using Schwann cell bridges or cAMP strategies in spinal cord-injured animals,” said Naomi Kleitman, Ph.D., program director of the U.S. National Institute of Neurological Disorders and Stroke (NINDS, Bethesda, WA, USA). The study was funded in part by NINDS.

The therapies in this study were selected for their likely feasibility in humans. Rolipram, for example, has already been tested in clinical trials for other disorders, and Schwann cells can be grown from a patient's own peripheral nerves.

Follow-up studies are now being planned to confirm the results and to try to learn more about how the triple therapy works, said Mary Bartlett Bunge, Ph.D., who conducted the study along with colleagues at the University of Miami School of Medicine. Their studies might also lead to the development of better drugs to prevent the breakdown of cAMP, she added.

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Related Links:
University of Miami Medical School
Institute of Neurological Disorders and Stroke