The mystery of why multiple sclerosis (MS) tends to go into remission while women are pregnant may be the secret to overcoming the devastating neurodegenerative disease, according to University of Calgary researchers who have shown that a pregnancy-related hormone is responsible for rebuilding the protective coating around nerve cells.
In a paper to be published in the February 21 issue of The Journal of Neuroscience, a team of researchers from the U of C's Faculty of Medicine reports that a study conducted on mice found that the hormone prolactin encourages the spontaneous production of myelin, the fatty substance that coats nerve cells and plays a critical role in transmitting messages in the central nervous system. A collaboration between the laboratories of Drs. Samuel Weiss and V. Wee Yong of the Hotchkiss Brain Institute, the study is the first to determine that prolactin, which increases in the body during pregnancy, is directly responsible for the formation of new myelin in the brains and spinal cords of pregnant mice. Further, when non-pregnant mice with MS-like lesions were injected with prolactin, their myelin was also repaired.
The research was based on evidence that MS, which is more common in women than men, goes into remission when women become pregnant. MS is a neurodegenerative disease where the body's own immune system attacks the myelin surrounding nerves, leading to progressive loss of sensation and movement. MS affects approximately 2.5 million people worldwide and Canadians have one of the highest rates of the disease in the world.
"It is thought that during pregnancy, women's immune systems no longer destroyed the myelin," said Weiss, director of the Hotchkiss Brain Institute and senior author of the study. "However, no previous study has tested whether pregnancy actually results in the production of new myelin, which may lead to improvement of symptoms." The paper's findings represent the first example of a natural, biological mechanism that produces new myelin in the adult brain and spinal cord and identifies prolactin as a potential therapeutic substance for future testing in people with MS.
"Agents promoting remyelination will be beneficial not only for typical demyelinating diseases like MS," says Dr. Fred (Rusty) Gage, of the Salk Institute, "but also for many other neurological disorders, such as spinal cord injuries and stroke." Gage, an international leader in nervous system repair, was not involved in this study.
Subsequent tests of prolactin in animal models of MS will be required before testing of prolactin on humans can take place, but MS researchers are hopeful human trials can take place within the next several years.
"This discovery has the potential to take MS therapy a step further than current treatments that stabilize the disease in its early stages. By promoting repair, which is the goal of prolactin therapy, we have hope of actually improving symptoms in people with MS," says Dr. Luanne Metz, director of the Calgary MS Clinic in the Department of Clinical Neurosciences, University of Calgary and Calgary Health Region.
The study, authored by Weiss, Christopher Gregg, Viktor Shikar, Peter Larsen, Gloria Mak, Andrew Chojnacki and Yong, compared pregnant and virgin female mice of the same age and found that pregnant mice had twice as many myelin-producing cells, called oligodendrocytes, and continued to generate new ones during pregnancy. By chemically destroying myelin around nerve cells, the researchers found that pregnant mice had twice as much new myelin two weeks following the damage as virgin mice and that introducing prolactin mimicked the effects of pregnancy on myelin production and repair in mice that weren't pregnant.
"The results of this study should be well received by people living with MS today," said Dr. William McIlroy, national medical advisor for the Multiple Sclerosis Society of Canada. "It represents a new insight of how we might be able to reverse some of the effects of the disease and improve the quality of life for those who live under its influence."
The study was funded by the Canadian Institutes of Health Research and the Multiple Sclerosis Society of Canada, with the support of the Alberta Heritage Foundation for Medical Research and the Stem Cell Network.
The journal article "White matter plasticity and enhanced remyelination in the maternal CNS" will be published in the Feb. 21 issue of The Journal of Neuroscience. The journal is published by the Society for Neuroscience, an organization of more than 36,500 basic scientists and clinicians who study the brain and nervous system.
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