Inflammation / MS

ironjustice@aol.com · medicine forum Guru Joined: 28 Apr 2005 Posts: 1522

Selectively Blocking Inflammatory Signals May Protect Mice From MS

Main Category: Multiple Sclerosis News
Article Date: 14 May 2006 - 3:00am (PDT)

A new way to preserve the cells that surround and protect nerves could
lead to new treatments for demyelinating diseases such a multiple
sclerosis, a research team reports in the May 2006, issue of the
Journal of Neuroscience.

The approach grew out of a novel explanation, quickly gaining
followers, for the mechanism of nerve damage caused by multiple
sclerosis. Instead of concentrating on the alterations that result in
autoimmune assaults on the nervous system, researchers led by Brian
Popko of the University of Chicago have focused on a set of factors
that prevent recovery from the inflammatory attacks.

A series of papers from Popko's lab has demonstrated that
interferon-gamma -- a chemical signal used to activate the immune
system -- plays a critical role in damaging the cells that produce
myelin, the protective coating that lines healthy nerves. Interferon
not only leaves these cells, called oligodendrocytes, incapable of
repairing the damage but can also kill them directly.

"Interferon-gamma is not normally found in the nervous system," said
Popko, the Jack Miller Professor of Neurological Diseases at the
University of Chicago, "but it can gain entry after an inflammatory
flare-up. We previously showed how it harmed oligodendrocytes. Here we
confirm its direct harmful effects on those cells and demonstrate one
way of protecting them."

The researchers produced a series of transgenic mice. In one set they
introduced genes that produced interferon-gamma within the central
nervous system. In another set they also introduced a gene (known as
suppressor of cytokine signaling 1, or SOCS1) that blocked the response
of myelin-producing cells to interferon-gamma.

Although transgenic mice with low levels of interferon-gamma showed no
symptoms of nervous system damage, 18 out of 20 mice exposed to higher
interferon levels developed difficulty walking, including mild to
moderate tremors, within two weeks of birth. Only four out of 20 mice
with both high interferon levels and the SOCS1 gene had symptoms.

On autopsy, mice with high interferon levels in the nervous system had
severe loss of oligodendrocytes, ranging from 20 to 40 percent. Those
with the protective SOCS1 gene lost only eight to 15 percent.

High interferon levels were also associated with loss of myelin sheaths
around nerve connections and unprotected axons in the brain. Again,
SOCS1 was able to reduce the damage.

"Together," the researchers wrote, "these data demonstrate that
oligodendroglial expression of SOCS1 protects mice from the clinical
and morphological consequences of IFN-gamma expression in the central
nervous system during development."

"We found this tremendously encouraging," said Popko. "SOCS1 prevented
or reduced the harmful effects of interferon gamma on myelin-producing
cells. This study solidifies our suspicions about interferon's specific
role in demyelinating disease and suggests ways to block it."

Although there is currently no reliable way to deliver SOCS1 directly
to the nerves of a patient with multiple sclerosis, this protective
approach could be combined with stem cell therapy to repair nerve
damage. Several research groups are already studying the use of stem
cells to repair damaged myelin sheaths, but in the long term those stem
cells would be vulnerable to ongoing immune-mediated damage.

But if stem cells could be engineered to resist harmful signals such as
interferon-gamma, they might be protected from the "harsh environment"
present in immune mediated demyelinated lesions, said Popko.

###

The National Institutes of Health and the Myelin Repair Foundation
supported the research. Additional authors include Roumen Balabanov and
Ji Yeon Lee of the University of Chicago, Krystal Strand of the
University of North Carolina, and April Kemper of Wake Forest
University.

Contact: John Easton
University of Chicago Medical Center

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