Teams Funded by the National MS Society
Report on Key Enzymes Related to MS Progression and Nervous
System Repair
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Medical Update Memo
October 27, 2008
Summary
Two teams of researchers funded by the National
MS Society have reported findings on nerve
tissue injury and repair that add important
information needed to stop MS progression and
develop nervous system repair strategies.
Details
Isobel Scarisbrick, PhD (Mayo Clinic and Foundation,
Rochester, MN) and colleagues have found two
enzymes that may serve as markers of progressive
MS and nerve fiber injury. Patrizia Casaccia,
MD, PhD (Mount Sinai School of Medicine, New
York) and colleagues reported that another
enzyme is essential for replenishing myelin-making
cells that have been depleted by MS. Both teams
are continuing these lines of research in hopes
of identifying targets for the development
of new therapies for MS.
Dr. Scarisbrick reported her team's findings
related to MS progression at the annual meeting
of the American Neurological Association
(Abstract T-99). Dr. Casaccia's report on
the enzyme critical for repair appeared in
Nature Neuroscience (early online publication,
August 24, 2008).
Progressive MS and KLK enzymes (Dr.
Scarisbrick's team): Understanding
the processes that lead to tissue damage
in MS is crucial to feed parallel
efforts to protect and repair the brain and
spinal cord. Dr. Scarisbrick previously found
elevated levels of "KLK6" (a newly
identified member of the kallikrein enzyme
family) in areas of damage found in tissue
samples from people with MS. Now, in a follow-up
study, the group has studied the levels of
KLK6 and other kallikreins in blood samples
taken from 35 people with different clinical
courses of MS and 62 controls without MS.
The results show that KLK1 and KLK6 were elevated
in people with MS, with the highest levels
appearing in people with secondary-progressive
MS (a course of MS that initially is relapsing-remitting
and then becomes progressive, with or without
occasional relapses and minor remissions).
The team also exposed nerve cells isolated
from mice to KLK1 or KLK6 in the laboratory,
and found that the enzymes promoted nerve cell
loss. Dr. Scarisbrick is continuing to study
the role of these enzymes in nerve fiber injury
and hopes to find a way to target them with
therapeutic strategies for people with progressive
MS.
Repair and HDAC enzymes (Dr. Casaccia's
team): MS involves immune attacks against brain
and spinal cord tissues, primarily myelin,
the insulation that surrounds and protects
nerve fibers. Several studies have indicated
that, early in the disease, immature myelin-making
cells - called, "oligodendrocyte progenitors" -
are recruited to generate new myelin. A sufficient
number of these cells is needed so that progenitors
can migrate to the site of myelin damage
and develop into myelin-making cells. Then,
genes that instruct the formation of myelin
components are activated and myelin is formed.
In MS, this process fails. Dr. Casaccia is
studying whether some molecules may inhibit
the activation of the genes that promote
myelin formation.
In this study, Dr. Casaccia's team observed
the gene activity during oligodendrocyte development
in mice with damaged myelin. They found that
enzymes called histone deacetylases (HDACs)
were crucial to this process, particularly
HDAC1 and HDAC2. Deleting these two enzymes
impaired the differentiation of oligodendrocyte
progenitors, that is, the process by which
these cells develop a more specialized form
or function. The team is studying how these
findings might be translated into therapeutic
strategies.
With information from the National MS Society
(USA)
National Research and Programs
Clinical Programs
Offert en français.
Disclaimer
The Multiple Sclerosis Society of Canada is an independent, voluntary health
agency and does not approve, endorse or recommend any specific product or therapy,
but provides information to assist individuals in making their own decisions.
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