MONDAY, Nov. 19, 2001 (HealthDayNews) -- A mutant protein in mice seems to protect them against the rapid deterioration that normally happens in nerve cells after an injury, and people may have a similar mechanism, says a new study.
The gene mutation is known as Wld, and, in mice, it allows nerve axons -- the long "tails" of nerve cells -- to live much longer than normal after nerve cell injury, reports an international group of researchers. The findings could mean new therapies for all kinds of nerve damage, from injury to diseases, although such treatments are years away, say the researchers,.
"When we say mutation, we shouldn't always think that that's something bad. This appears to be a good mutation," says senior study author Michael Coleman.
About 10 years ago, two of Coleman's colleagues at England's University of Oxford discovered a mutant mouse in which nerve axons were protected from wallerian degeneration, a condition first described in 1850 in which the distant end of a nerve axon deteriorates after an injury to the nerve cell. The axon and its protective sheath both break apart. The degeneration is similar to what happens in the nerve cells of people with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, multiple sclerosis and injuries to their spinal cords.
Normally, the end of the nerve axon most distant from the cell nucleus degenerates in 24 to 48 hours after an injury, but in the mutant mouse, the axons survived for several weeks.
After a decade of research on successive generations of mice with that ability, the researchers identified the specific mutated gene responsible for the protective effect.
"It is possible that humans would have something related
which nevertheless could be protective," says Coleman, who now leads the Molecular Neurobiology group at the University of Cologne, in Germany.
"There's every reason to expect that humans would have some kind of related gene -- certainly not quite the same gene because it's a very unusual mutation. But once we understand enough about how this works in the mouse, we'll be able to identify similar processes in humans," Coleman says.
"The degeneration of nerves in many [human] neurodegenerative diseases follows what looks like a very similar process," says Coleman. "We hope that by identifying this gene, it has the potential for protection not only in this injury model but also in other disease types, possibly such as ALS and maybe multiple sclerosis."
The researchers are searching for similar genes in humans. "Now we have to look through the population and see whether there are some people who have alterations in those genes and therefore may be protected from kinds of neurodegenerative disease," says Coleman.
The study will be lengthy, but the researchers say they are encouraged by early tests that show that breeding mice with the mutation with mice which have the equivalent of the human neurodegenerative diseases appears to produce offspring protected from those diseases.
Coleman says the research has potential applications for chemotherapy patients, whose treatment often is limited because cancer drugs can damage their nerves.
"If we can move towards any kind of drug with this, it might be possible to give that drug in advance when you know that several hours or one day later, there's going to be this chemotherapy regime, which is toxic to neurons," he says.
Mark Bisby, a neuroscientist at the Canadian Institutes of Health Research in Ottawa, Ontario, says the findings solve a long-standing biological mystery about what protects these mutant mice from nerve trauma.
"What [these findings] have the potential to do ultimately would be to provide us with some approaches to therapy that could stop this process of degeneration in its tracks, so that the need to completely regrow a whole new nerve isn't necessary," says Bisby.
The researchers say they found large quantities of the Wld protein in nerve axons but not in the nucleus of the nerve cells, suggesting that the protein regulates a protective mechanism, rather than directly prevents degeneration.
Coleman says the next step is to test the gene in other animal models. If it works, researchers then face the challenge of finding a drug that does the same job as the protein without producing side effects.
"One bit of good news is that this mouse that has the protective mutation is otherwise absolutely normal, " says Coleman. "So that suggests that if we can find a drug that mimics this process well enough, then we might also see few side effects in humans."
What To Do
For more about neurodegenerative diseases and nerve trauma injuries, check the ALS Association, the National Multiple Sclerosis Organization or the Brain Injury Association.
For a technical explanation of wallerian degeneration, check the Uppsala University Web site.
