By Sean Henahan, Access Excellence

On the west coast, researchers at UCSD School of Medicine are reporting the first successful use of gene therapy in animals to achieve partial recovery from spinal cord injuries. The investigators utilized gene therapy to encourage damaged nerve cells in in laboratory rats to produce a growth factor that stimulated regrowth of nerve tissue.

Caption: UF's Dr. Rick Fessler at work

"This novel use of gene therapy provides the opportunity for injured axons to regenerate through the spinal cord and restore function," said Mark H. Tuszynski, M.D., Ph.D., associate professor of neurosciences at the UCSD School of Medicine.

Under normal circumstances, once the spinal cord of an adult mammal is cut, the nerve tissue does not recover, and paralysis results. Tuszynski and his colleagues showed in earlier work that injured spinal cord cells can be stimulated to regrow when exposed to certain nerve growth proteins. In the current study, the researchers were able to culture skin cells from rats with spinal cord injuries and genetically modify the cells to produce the growth factor neurotrophin-3 (NT-3). Upon grafting back into the animal, the modified cells secreted NT-3 at the site of spinal cord injury. This stimulated axon regrowth and resulted in some recovery of walking ability. In addition, the genetically modified cells were also found to deliver NT-3 continuously for several months, further enhancing the regeneration of injured axons and the partial restoration of function.

"The goal in spinal injury research is to promote the regrowth of cut or damaged axons," said Tuszynski. "These results indicate that cellular delivery of NT-3 through gene therapy can restore function by promoting the sustained growth of axons after spinal cord injury."

FIRST NERVE TISSUE TRANSPLANT TO TREAT MAN WITH SPINAL INJURY

Meanwhile, in Florida, researchers report having performed the nation's first nerve tissue transplant on a paralyzed man to slow the progression of spinal cord damage.

The researchers injected small pieces of human embryonic spinal cord cells directly into an expanding cavity that sometimes forms at the site of a specific type of spinal cord injury. Neurosurgeons at the University of Florida Brain Institute performed the procedure to test the safety and feasibility of embryonic spinal cord grafts, which in animal studies have been shown to help cats regain some use of their paralyzed limbs.

"Our primary goal in this first clinical experience is to test whether these grafts can survive and, if so, to what extent they can fill the cavity in the human spinal cord as they have in our animal studies," said UF neurosurgeon Richard Fessler, who performed the transplant. "We are advising patients that our primary goal in this pilot study is not to restore lost mobility or feeling, but to plug the expanding cavity and prevent further spinal damage."

The test is an important first step in developing a future treatment that can restore at least partial use of limbs or organs left paralyzed by a crushing spinal cord injury, say the researchers.

"Our first clinical experience will reveal a lot about cellular transplantation in humans, particularly about the effects of short-term, drug-induced immune suppression [so the body will accept the foreign tissue], how long it takes for the grafted tissue to grow and how much transplanted tissue is needed to plug the spinal lesion," said UF neuroscientist Douglas Anderson. "You can only answer so many questions in animal studies. If this procedure is successful and causes no adverse consequences to our first patients, it will help us reach our goal faster to aid the recovery of many people disabled by spinal cord injury."

The patient receiving the experimental treatment is the first of 10 paralyzed volunteers who will undergo the procedure as part of a four-year pilot study at the University of Florida. Three days after the 12 hour surgery, the patient is reported to be in serious, but stable, condition. UF neurosurgeon Richard Fessler, who performed the transplant, estimated that it will take at least six months--and possibly as long as a year--before scientists can determine whether the tissue graft is surviving and successfully plugging the wound cavity in the effort to prevent deterioration of the patient's functioning.

Only patients who have a chronic disorder called syringomyelia are being considered for the transplant. The condition is characterized by expansion of a fluid-containing cavity within the damaged spinal cord that can cause unbearable pain and progressive loss of sensation and movement. Study participants will be rigorously screened so any existing spinal function or high recovery potential will not be placed at risk.

Patients will receive the tissue grafts while undergoing standard syringomyelia surgery, which exposes the spinal cord and drains the cavity through a tube. Many patients must undergo the treatment repeatedly.

The embryonic spinal cord graft was obtained from aborted tissue, 6 to 9 weeks old, which otherwise would have been discarded. Researchers said they used such tissue because of its exceptional ability to grow and fill cavities, and because it develops into all of the cell types normally seen in the adult spinal cord. Researchers  are also exploring alternatives to embryonic tissue in spinal-cord repair, including laboratory-grown cells and grafts using other nerve tissue cell types.

Neuroscientists are increasingly hopeful that embryonic tissue transplants also could offer promising advances in the treatment of Parkinson's, Alzheimer's, Huntington's, epilepsy, diabetes, leukemia and other debilitating and deadly conditions.

"Everybody talks about a cure for crippling spinal cord injury," Reier said, "but our philosophy is there's no single 'magic bullet' that will make someone get out of the wheelchair and walk. It will take a combination of approaches. At this point, no other technique has received the degree of scrutiny and work that embryonic tissue transplants have in actually restoring function of a damaged spinal cord."

The UCSD gene therapy findings appear in the July 15 issue of The Journal of Neuroscience. The University of Florida information was released to the press by the University of Florida.