In 1986, an unknown disease began killing monkeys at the Oregon National Primate Research Center in Hillsboro. Affected animals developed an unsteady gait and a rapidly advancing paralysis of the limbs. Caregivers could do nothing to stop the disease and euthanized most of the helpless animals within a week of symptom onset.
The disease, researchers now report, is the monkey equivalent of multiple sclerosis. And it appears to be caused by a virus – adding support to the possibility that multiple sclerosis in humans can be triggered by a viral infection. Experts say the discovery could help expedite the search for more effective treatments. "That's the ultimate goal," said co-author Scott Wong, a scientist at the primate center and Oregon Health & Science University's Vaccine and Gene Therapy Institute.
Since the first case appeared at the primate center, 56 monkeys in the Japanese macaque colony have fallen ill with the neurological disease. In most years, no more than four cases appear in the population of more than 300 monkeys. In a few cases, the monkeys recovered and lived normally for many months before relapsing -- a course often seen in people with multiple sclerosis, or MS.
Wong and colleagues studied brain and spinal cord samples from nearly all of the monkeys after death. Microscopic examination revealed damage very similar to that in MS patients, including nerve fibers stripped of their protective sheath. Brain scans performed on eight living monkeys showed scattered patches of dead and damaged nerve cells also similar to those seen in people with MS.
The researchers isolated a previously unknown virus from a sample of damaged spinal nerve tissue taken from one animal. DNA analysis showed that the virus belongs to the herpes family of viruses. Wong's team developed a sensitive test for the virus and used it to screen samples from healthy and diseased monkeys. So far, they have detected the virus in samples of damaged nerve tissue from six monkeys that died from the disorder. The virus has not showed up in healthy samples.
"Whether or not a similar virus might actually cause MS, that's the big issue," said Dr. Dennis Bourdette, a co-author of the study and director of OHSU's multiple sclerosis center.
Scientists have spent decades trying to find out whether viruses play a role in triggering multiple sclerosis. So far, the evidence for a viral cause has fallen short. Still, many researchers suspect that a viral infection could be one of the factors that drive the immune system to mount a misdirected attack on the protective sheath around nerve fibers.
Using the sensitive tests developed by Wong, Bourdette said his team is preparing to screen samples from people with MS to look for human-adapted viruses related to the monkey virus. He said the search shouldn't take longer than 18 months. If such a virus exists -- and it proves to be a triggering factor in multiple sclerosis -- Bourdette said researchers could begin developing a preventive vaccine. The National Institutes of Health funded the research.
Dr. Kenneth L. Tyler, a professor neurology at the University of Colorado Denver who was not involved with the research, said much work remains to establish the role of viruses in multiple sclerosis.
"It is feasible that something similar in humans is occurring, although this study does not prove it," Tyler said. He noted that the researchers have yet to present definitive evidence that the monkey virus is the cause of the MS-like disease. For instance, he said, researchers must show that exposing healthy monkeys to the virus will reliably produce the disease.
But even if the viral connection doesn't pan out, Tyler said the discovery of the MS-like disease in Japanese macaques is significant because it gives researchers a better animal model for testing treatments because it is a naturally occurring disease – not a condition contrived by laboratory manipulation.
"This is a very exciting and interesting animal model," Tyler said.