Mayo Clinic researchers discover enzyme has potential to stop multiple sclerosis tissue damage

May 24, 2002

ROCHESTER, MINN. -- Mayo Clinic researchers have found a new clue in the search for a way to stop the tissue damage, or demyelination, that occurs in multiple sclerosis (MS) or related central nervous system diseases. They found a dramatic increase in a newly discovered degradative enzyme, myelencephalon-specific protease (MSP), in demyelinated tissue, indicating that inhibiting this enzyme could potentially block the process of tissue damage.

This is a first-ever finding of the link between MSP and the debilitation that patients experience in MS.

This study will be published in the June 2002 issue of Brain, published by Oxford University Press,

"If you could control this enzyme, you could possibly decrease the development of disease," said Isobel Scarisbrick, Ph.D., Mayo Clinic neuroscientist and lead author of this study. "Excess MSP, as is present in inflammatory central nervous system lesions such as those in MS, may promote demyelination."

Dr. Scarisbrick and colleagues discovered MSP in 1997 while she was a research fellow at Mayo Clinic in Jacksonville, Fla. They cloned MSP and developed probes and other tools to work with the enzyme and attempt to determine its role in demyelination.

In the researchers' investigation of mouse and human MS tissue, they discovered MSP's dramatic increase in inflammatory cells in actively demyelinating human MS lesions. MSP is a multifunctional enzyme, facilitating entry of inflammatory cells into the brain and also contributing to tissue destruction when overexpressed. It also may harm processes of the oligodendroglia, cells found in the central nervous system that form the myelin sheath protecting the axon, a component of nerve cells. When functioning normally, however, MSP contributes to proper oligodendroglia function.

In the MS field, researchers have made many strides in learning about the genetics, origin and development of the disease, but no treatment has yet been found to be effective in treating all MS cases. Dr. Scarisbrick and colleagues view their new findings cautiously and not as a panacea, but yet are hopeful about the possibilities for future treatment development.

"We're not reporting this as a cure, but it represents something that could be targeted for therapy," says Dr. Scarisbrick. "We have a lot more work to do." Her colleague, Moses Rodriguez, M.D., Mayo Clinic neurologist, concurs. "This is a very important enzyme," says Dr. Rodriguez. "It really has therapeutic potential."
This study was supported by a pilot study grant from the National Multiple Sclerosis Society.

MS is an inflammatory demyelinating central nervous system (CNS) disease. It occurs most commonly in those between the ages of 20 and 40, and it is the most frequent neurological disorder in young adults in North America and Europe. Approximately 330,000 people in the United States have MS. Though researchers are still investigating the precise causes of MS and related CNS diseases, it is thought to be an autoimmune disease resulting from a triggering of the body's own immune system to destroy the myelin sheath covering the nerve fibers.

Lisa Copeland
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Mayo Clinic

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