Thomas Herwig
507-266-0189 (days)
507-284-2511 (evenings)
[email protected]
For Immediate Release Mayo Clinic Researchers Discover Genes Associated With Neurological Damage in a Model of Multiple Sclerosis ROCHESTER, MINN. Ê Researchers at Mayo Clinic have discovered a family of genes linked to neurological damage in a laboratory model of multiple sclerosis (MS). The discovery of these genes represents a significant step forward in understanding the mechanisms by which immune cells cause damage in MS and potential new strategies for treatment. An article describing the discovery, and the potential mechanism involved in MS damage, appears in this monthÃs edition of the journal Nature Medicine.
Dr. Moses Rodriguez, a Mayo Clinic neurologist and professor of immunology and molecular neuroscience, commented, ìWe have been able to identify for the first time a family of genes that may be associated with the damage caused by MS. We now believe that the presence or absence of these genes in our animal model of MS may explain why one-third of persons with MS show little or no deficit from the disease, while the other two-thirds are more seriously affected. The discovery has important implications to the pathogenesis of neurological deficits in MS and holds promise for future therapeutic strategies.î
The five-year study implicates a family of genes present in all humans, known as MHC class I (major histocompatibility complex class I), in MS damage. In the study, a virus was introduced to two groups of transgenic mice of an identical genetic background to induce an MS-like disease. Both groups developed the loss of myelin on nerve fibers, or lesions, that are characteristic of MS. But despite the lesions, only one group showed signs of continuing neurological abnormality. ìBy knocking out the MHC class I genes in one group of mice,î said Dorian McGavern, a researcher at the Molecular Neuroscience Program that conducted the study, ìwe prevented these mice from having neurological abnormalities. Nerve fibers, or axons, were damaged in mice with neurologic deficits. However, mice deficient in MHC class I had preserved nerve fibers. We knew we had found something significant: a potential mechanism for the damage seen in MS.î (See attached graphic.)
Recent research has confirmed the long held belief that damage to nerve fibers, and not damage to myelin alone, contributes to the lasting impact of MS disease. What has been missing is the answer to why this is so. Dr. Rodriguez explained, ìThis study gives a clue as to why, it explains the potential mechanisms that are involved. It is a story of how one component of the immune response, killer T-cells, secrete factors that accidentally destroy nerve fibers while attempting to fight the disease.î
Mayo researchers are working to identify the specific immune factors that cause damage to the nerve fibers. ìBy blocking these factors in humans with MS,î Dr. Rodriguez added, ìwe may be able to prohibit or lessen the long-term damage to nerve fibers from occurring. Additionally, this may result in the discovery of a beneficial therapy besides interferon drugs.î
Currently, interferon drugs (known for their ability to fight virus infection) are widely prescribed for those in the early stages of relapsing-remitting MS, a form of the disease where neurological symptoms come and go. In addition, trials are underway now to determine their use in an even broader group of patients considered to be ìpossibleî for developing the disease. Dr. Rodriguez added, ìIf we can focus treatment for those MS patients who are expected to do poorly, we could save those who are expected to fair better with MS from the long-term side effects of these (interferon) medicines.î
MS is a disease affecting an estimated 400,000 persons in the United States, an estimated 1.25 million worldwide, and whose incidence and prevalence may be increasing.
NOTE: For more information, a copy of the original study and requests for interviews, contact Tom Herwig, Mayo Clinic Division of Communications, at 507-266-0189. For television, a 10- to 15-second color video presentation of the photograph appearing in this news release and illustrating a new understanding of the mechanism of MS damage is available on request. Also available is a bound booklet containing the five-part symposium on Multiple Sclerosis that was published in the journal Mayo Clinic Proceedings in 1997 and 1998.
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