Potential new target for multiple sclerosis therapy

Mar 28 2008, 12:47 PM EST
Potential new target for multiple sclerosis therapy


EUREKALERT
Contact: Nick Zagorski
nzagorski@xxxxxxxxx
301-634-7366
American Society for Biochemistry and Molecular Biology


Researchers demonstrate both genetic and pharmaceutical evidence for the
role of a protein called collagenase-2 in the development of multiple
sclerosis (MS), providing a potential new way to combat this debilitating
disease.


Collagenase-2 is a member of a protein family called matrix
metalloproteinases (MMPs, collagenase-2 is MMP8), a large group of enzymes
that break down collagen and other components of the body's connective
tissue. MMPs have been implicated in contributing to MS by degrading the
tissue that maintains the blood-brain barrier, thus allowing unwanted cells
to invade and break down nerves. In fact, MMPs are found in elevated amounts
in the blood and spinal fluid of diseased individuals.


Using a mouse model of MS, Carlos Lopez-Otin and colleagues performed two
analyses on MMP8 to determine how relevant this protein is to the disease.
First, they developed mutant mice deficient in the gene for MMP8 and found
that these mice had a fewer invading cells in the brain, fewer damaged
nerves, and a general improvement in their clinical profile.


They also gave diseased mice a drug that blocked MMP8 activity and found
that this, too, could reduce the severity of disease symptoms. Taken
together, these promising findings provide the first causal evidence for
MMP8 in the development of MS, and offer a new therapeutic target.


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This story appears in JBC online on March 28.


Corresponding Author: Carlos Lopez-Otin, Department of Biochemistry and
Molecular Biology, Universidad de Oviedo, Spain; Phone: 34-985-104201,
E-mail: clo@xxxxxxxxx


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