More MS news articles for May 2002

Enzyme Linked to MS Nerve Damage

It shows up at site of nerves being stripped of their protective coating

May 28,2002
By Adam Marcus
HealthScoutNews Reporter

FRIDAY, May 24 (HealthScoutNews) -- Scientists have found what may be a "smoking gun" substance that generates the trademark nerve damage associated with multiple sclerosis.

The substance, an enzyme called myelencephalon-specific protease (MSP), shows up prominently at sites where immune cells are stripping nerves of their protective protein-and-fat sleeves. When applied to nerve-coating cells, the enzyme dramatically alters their ability to lay down adequate amounts of this sheath, known as myelin, the scientists say.

"You could consider [MSP] to be a smoking gun," says Michael Blaber, a biochemist at Florida State University and a co-author of the study on the new research. The enzyme shows up at the scene of the crime, although no one has seen it pull the trigger, he says.

In theory, Blaber adds, blocking the enzyme might prevent or reduce the damage from multiple sclerosis, although the research is still a long way off from being clinically applicable.

A report on the researchers' findings appears in the June issue of the journal Brain.

Multiple sclerosis is marked by the gradual loss of myelin that surrounds nerves and helps them conduct electrical signals. Once stripped of this fatty, protein-rich shield, the nerves can't properly transmit impulses, leading to severe muscle and motor problems. Multiple sclerosis afflicts an estimated 350,000 Americans, according to the National Institutes of Health.

MSP belongs to a family of enzymes called proteases, whose job is to cleave proteins. Some proteases snip proteins to change their function or "activate" them, while others are "digestive," chewing them up to break them down. MSP falls into the second category.

The enzyme was discovered in 1997 by Isobel Scarisbrick, a neurologist at the Mayo Clinic. Scarisbrick, lead author of the Brain study, found that MSP is only produced in the brain, in cells called oligodendrocytes that lay down myelin over nerve fibers.

In the new study, Scarisbrick, Blaber and their colleagues looked for MSP tissue samples of demyelinated nerves from people with multiple sclerosis, as well as in models of the disease in mice and marmosets, which are small monkeys.

MSP showed up in force in the immune cells that eat away myelin, the researchers found. "We were shocked to see" how much of the enzyme appeared, Scarisbrick says.

The researchers then made batches of MSP, and looked at the effects of excess MSP on oligodendrocytes. They found that while the enzyme didn't kill them, it stunted their ability to cover nerve fibers with myelin, passing a death sentence on those cells.

Finally, the researchers showed that MSP attacks key myelin proteins, a necessary step if it indeed damages nerve cells.

Scarisbrick says the latest work and her earlier research indicate that MSP run amok may jeopardize the brain in at least two ways. "It is capable of degrading myelin, and it also degrades proteins that form a barrier around the brain that keeps the immune cells out," she says.

Stephen Reingold, vice president for research programs at the National Multiple Sclerosis Society, which funded the study, says MSP could be a culprit in multiple sclerosis, but it's too soon to tell.

"How this is going to relate to human disease is less clear. And whether a mechanism will be developed that will protect the central nervous system" from the harmful enzyme is another matter still, Reingold says.

SOURCES: Isobel Scarisbrick, Ph.D., assistant professor, neurology, Mayo Clinic, Rochester, Minn.; Michael Blaber, Ph.D., associate professor, chemistry and biochemistry, Florida State University, Tallahassee; Stephen Reingold, Ph.D., vice president, research programs, National Multiple Sclerosis Society, New York City; June 2002 Brain

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