SCIENTISTS USE A VARIETY OF CELLS AND MOLECULES TO COAX REGROWTH OF DAMAGED NERVES

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SCIENTISTS USE A VARIETY OF CELLS AND MOLECULES TO COAX REGROWTH OF DAMAGED NERVES.

ORLANDO, Sunday, Nov. 3 - Step by step, scientists are making new advances in regenerating damaged nerves and nerve fibers - advances that may one day help people who have conditions or diseases in which nerve cells have become impaired or have ceased functioning entirely, including spinal cord injuries, blindness, stroke and multiple sclerosis.

One group of scientists, for example, has discovered that transplants of the ensheathing cells from the nerves that humans use to smell can help spinal cord damaged rats regain some of their ability to walk. Another group, also working with rats, has developed a synthetic peptide that promotes new nerve fiber growth in damaged spinal cords. In addition, scientists have found that transplants of a particular cell line can limit loss of vision in rats with retinal degenerative disease. The new studies were reported today during the 32nd annual meeting of the Society for Neuroscience.

Hans Keirstead, PhD, and his colleagues at the University of California-Irvine have found that transplanted human olfactory ensheathing cells (OECs) can help rats with injured spinal cords recover some ability to walk.

"This is the first time human OECs prepared in this high purity manner have been used to investigate their ability to treat the injured spinal cord," says Keirstead. "Because our study used human cells, it has direct significance for clinical use."

OECs are brain cells that enable our sense of smell. When injured, these cells are able to replace themselves - a very rare trait among brain cells. Usually, it's only young cells that are able to regenerate.

"OECs are thus considered a good candidate for the treatment of an injured brain or spinal cord," says Keirstead. In the past, scientists have investigated whether rat OECs are effective in treating injured spinal cords, but with mixed results. Some of the treated animals showed excellent recovery; others showed no recovery at all.

Keirstead and his colleagues wanted to determine what, if any, behavioral and cellular effect human OECs would have on injured spinal cords. They set up an experiment in which they transplanted human OECs into one group of spinal cord injured rats and did not treat another group of similarly-injured rats.

"We first observed that the injured animals transplanted with these human olfactory ensheathing cells were able to regain some walking ability," says Keirstead. "We also observed some regrowth of neurons in the injured spinal cords of the animals that had received the transplants - but not in the spinal cords of non-transplanted animals."

The scientists found that scar formation, which commonly occurs around injury sites and which prevents the growth of neurons, was present in both the transplanted and non-transplanted animals. But in the transplanted animals, some growth of neurons occurred despite the scarring. "This suggests that human OECs transplanted into an area of spinal cord injury provide some support that enables regrowth in an environment that would otherwise prevent it," says Keirstead.

The scientists also found that the human OECs not only survived the period through which the animals were kept alive, but that the cells migrated from the transplant site into its surrounding. Such an ability to migrate through the adult nervous system is a very rare trait, and suggests that the cells may be able to cause regrowth beyond the injury site.

Keirstead is now trying to better understand how human OECs permit the regrowth of neurons. "We're also evaluating the effects of these cells following transplantation into chronically injured spinal cords," says Keirstead. "This would allow us to determine if these human cells are good candidates for treating injuries that have taken place months and maybe even years earlier."

At Yale University, Stephen Strittmatter, MD, PhD, and his colleagues have developed a synthetic peptide that promotes new nerve fiber growth in the damaged spinal cords of laboratory rats, allowing them to walk better. The peptide, NEP1-40, promotes the growth by suppressing the effects of the "Nogo" gene, which has been identified as the gene that prevents the brain and spinal cord from rewiring themselves after an injury.

"We have developed a way to block Nogo action with a peptide that binds to the Nogo receptor, thus preventing it from doing its normal job," says Strittmatter. This finding could one day help people who have experienced a brain or spinal cord injury, a stroke, or who have a degenerative disease such as multiple sclerosis.

To examine whether NEP1-40 would block Nogo and promote nerve regrowth, Strittmatter and his colleagues administered the peptide to spinal cord injured rats for four weeks through a catheter inserted into the animals' spinal cords. "We found that a number of nerve fibers did grow back in the spinal cord and that the rats were able to walk better than without the treatment," says Strittmatter.

No drug has been developed to promote axon recovery in humans, so it's difficult to predict how well this peptide will work in people, Strittmatter cautions. Nor have any toxicology studies been conducted on NEP1-40. "Before moving to human trials, researchers must first determine whether this synthetic peptide can promote nerve fiber growth in animals weeks and months after injury and whether the compound is effective and safe for human use," he says.

Because damaged nerve fibers in the brain and spinal cord remain at the site of an injury, scientists have some reason to believe that NEP1-40 might promote growth in older injuries. "If we had some way to block these nerve regeneration inhibitors, the damaged fibers might grow back again," says Strittmatter. "Our findings thus suggest that this peptide might have significant therapeutic potential."

Experiments recently conducted by the laboratory of Ray Lund, PhD, of the University of Utah Health Science Center may lead to new therapies for two serious eye conditions that can cause blindness: age-related macular degeneration and retinitis pigmentosa.

More than 10 million Americans currently have age-related macular degeneration, a condition that affects central vision and that is the leading cause of blindness in people over the age of 55. Retinitis pigmentosa, a group of inherited diseases that affect the retina and that result in a progressive loss of vision, afflicts about 100,000 Americans.

Working in collaboration with the laboratory of Glen Prusky, PhD, at the University of Lethbridge in Alberta, Canada, Lund's team has found that transplantations of a human pigment epithelial cell line can limit the deterioration of vision in rats with retinal degenerative disease.

"You can't ask a rat how well it can see, so we had to devise a method of assessing their visual performance," Lund says. His lab did this by developing a visual water task, a combination of a typical alternate choice box and the Morris water maze. "The test is very accurate discriminator of visual performance," says Lund.

For their experiments, Lund and his colleagues used RCS rats, the most widely studied animal model of retinal degeneration. Human cell line cells were transplanted into the eyes of three-week-old rats. When the animals were six months of age or older, their vision was assessed using the visual water task. The cell-grafted rats as a group performed more than twice as well on the test as the sham-injected rats, but only half as well as sighted control rats.

"Our study also showed that cell lines can be used as a potential source of cells for transplantation, which obviates many of the logistical and ethical problems associated with using fresh fetal cells," Lund says.

Lund and his researchers intend to try similar experiments in larger animal models in preparation for human clinical trials.