Researchers Stop MS-like disease in Mice
by Targeting a Blood Protein
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Medical Update Memo
April 13, 2007
Summary
A new study funded in part by the US National
MS Society shows for the first time that blocking
a segment of fibrinogen – a protein essential
for blood clotting – reduces inflammation
and symptoms in mice with an MS-like disease,
apparently without interfering with normal
blood clotting. NMSS grantee Katerina Akassoglou,
PhD, and postdoctoral fellow Ryan A. Adams,
PhD, and colleagues report their findings in The Journal of Experimental Medicine (2007
Mar 19;204(3):571-82).
Details
Multiple sclerosis occurs when the immune system
attacks the brain and spinal cord, damaging
the myelin that insulates and protects nerve
fibres. Brain cells known as “microglia” participate
in this attack and are activated when the blood
brain barrier (BBB) – the lining of cells
that should protect the brain from intruders – breaks
down. As the BBB breaks down, a blood protein
called “fibrinogen” leaks into
the brain. In addition to its known role in
blood clotting, evidence is growing that fibrinogen
also participates in the immune response that
goes awry in MS. Dr. Akassoglou’s team
has uncovered evidence that fibrinogen directly
activates microglia, and has developed a method
of inhibiting fibrinogen in mice without compromising
its clotting capabilities.
The researchers first administered fibrinogen
to microglia isolated in lab dishes and found
that the protein activated the cells in dramatic
fashion. This activation specifically occurred
through “Mac-1,” a docking site
on microglia. Fibrinogen surrounded activated
microglia both in mice with the MS-like disease
EAE, and in brain tissue from people with MS
obtained via autopsy.
Dr. Akassoglou’s team genetically engineered
mice in which fibrinogen and Mac-1 did not
interact, and found that inducing EAE in these
mice resulted in less myelin damage and less
severe disease. They then administered a small
fragment of fibrinogen – which blocks
binding of normal fibrinogen to Mac-1 – to
mice with an MS-like disease after the first
attack of paralysis. This form of fibrinogen
does not block the protein’s interaction
with blood platelets, and so would not interfere
with clotting. Compared with untreated mice,
activation of microglia decreased, myelin damage
diminished dramatically, and the treated mice
recovered faster and did not experience further
relapses.
This study highlights the potential of a novel
strategy for inhibiting the immune attack in
MS and improving symptoms. Further study is
necessary to confirm these findings and to
build the information base needed to translate
them into a potential treatment strategy in
people with MS.
ASK MS Information System Code: 2.4.f
National Research Department
National Marketing and Communications Department
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