Repair Of Multiple Sclerosis Brain Damage May Be Possible

Date: Nov-01-2012In what they describe to the press as a "life-changer" for millions of people with the disease, researchers in the US report this week a study where they
discovered blocking an enzyme in the brain may help repair the damage associated with multiple sclerosis (MS), and other brain diseases.

The findings are due to be published online this week in the Annals of Neurology.
Myelin Damage
In MS, the protective sheath or myelin around nerve fibers is damaged or destroyed, disrupting the ability of nerve cells to communicate with each other. This
process, called demyelination, is what causes the range of sensory, movement and cognitive problems typical of the disease.

Lead researcher of the new study, Larry Sherman, a professor at Oregon Health & Science University, heads a lab that had been studying MS and other disorders
where myelin gets damaged for nearly 15 years.

Back in 2005, Sherman's team published a study in Nature Medicine reporting their discovery that a sugar molecule called hyaluronic acid appears to
play a key role in demyelination. They found large deposits of hyaluronic acid at sites of myelin damage in humans and animals, and suggested the sugar itself
stops remyelination, or repair of damaged myelin, by preventing the cells that form the myelin from differentiating at the damage sites.
Enzyme Prevents Myelin Repair
Now, in their latest findings, Sherman and colleagues propose that it is not hyaluronic acid, but the compounds it breaks down into when in the presence of an
enzyme called hyaluronidase, that prevents remyelination or myelin repair.

They found very high levels of the enzyme in brain lesions of patients with MS and in the nervous systems of mice with an MS-like disease.

When they blocked the activity of the enzyme in the mice with the MS-like disease, myelin-forming cell differentiation was restored.

But perhaps the more significant result of the study was that the drug the researchers used to restore myelin repair, also led to improved nerve cell
function.
New Target for Drugs to Promote Myelin Repair
"What this means is that we have identified a whole new target for drugs that might promote repair of the damaged brain in any disorder in which demyelination
occurs," says Sherman in a statement.

"Any kind of therapy that can promote remyelination could be an absolute life-changer for the millions of people suffering from MS and other related disorders,"
he adds.

Sherman, who is also a senior scientist in the Division of Neuroscience at the Oregon National Primate Research Center, says the next step is to develop a drug
that specifically targets the effect of hyaluronidase.

He says the drug they used in the study would not be suitable for humans because it has potentially serious side effects. But a drug designed just for
blocking hyaluronidase would most likely have few, if any, side effects he suggests.

The findings are likely to impact research and drug development for MS and a range of other disorders involving demyelination, including complications arising
from premature birth.
Not a Cure
Sherman also makes the point that blocking the enzyme does not constitute a cure for MS. Other factors could be contributing to demyelination in MS and
related diseases. But the discovery of the enzyme, and finding a way to block it, may at the very least "lead to new ways to promote the repair of brain and spinal
cord damage either by targeting this enzyme alone or by inhibiting the enzyme in conjunction with other therapies," he says.

Grants from the National Institutes of Health, Fast Forward, LLC (a subsidiary of the National Multiple Sclerosis Society), the Laura Fund for Multiple Sclerosis
Research, the March of Dimes Birth Defects Foundation and the American Heart Association, helped fund the study.

Written by Catharine Paddock PhD

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