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Member
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Join Date: Jan 2008
Location: Maryland outside WASH DC
Posts: 258
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Member
Join Date: Jan 2008
Location: Maryland outside WASH DC
Posts: 258
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In RR MS the MMP-9 and friends do a LOT of the damage. They cut a hole in the BBB - Blood Brain Barrier then enter along with a LOT of other "things that do not belong inside" and then the MMP-9s cut the mylin into three basic components that the other folks dine on.
In addition they (the mmp-9s) like to destroy/"kill" Avonex!!!
Quote:
Lancet Neurol. 2003 Dec;2(12):747-56.
Functional roles and therapeutic targeting of gelatinase B(MMP-9) and chemokines in
multiple sclerosis.
Opdenakker G, Nelissen I, Van Damme J.
GO, IN, and JVD are at the Rega Institute for Medical Research, University
of
Leuven, Belgium
Multiple sclerosis (MS) is a demyelinating disease of the CNS of unknown
cause. Pathogenetic mechanisms, such as chemotaxis, subsequent activation of
autoreactive lymphocytes, and skewing of the extracellular proteinase
balance, are targets for new therapies.
Matrix metalloproteinase gelatinase B (MMP-9) is upregulated in MS and was
recently shown to degrade interferon beta, one of the drugs used to treat
MS.
Consequently, the effect of endogenously produced interferon beta or
parenterally given interferon beta may be increased by gelatinase B(MMP-9)
inhibitors. Blockage of chemotaxis or cell adhesion molecule engagement, and
inhibition of hydoxymethyl-glutaryl-coenzyme-A reductase to lower expression
of gelatinase B(MMP-9), may become effective treatments of MS, alone or in
combination with interferon beta. This may allow interferon beta to be used
at lower doses and prevent side-effects.
PMID: 14636780 [PubMed - in process]
1: Brain. 2003 Jun;126(Pt 6):1371-81.
Gelatinase B/matrix metalloproteinase-9(MMP-9) cleaves interferon-beta and is a
target for immunotherapy.
Nelissen I, Martens E, Van den Steen PE, Proost P, Ronsse I, Opdenakker G.
Rega Institute for Medical Research, Laboratory of Molecular Immunology,
University of Leuven, Leuven, Belgium.
Parenteral administration of interferon (IFN)-beta is one of the currently
approved therapies for multiple sclerosis. One characteristic of this
disease is the increased production of gelatinase B(MMP-9), also called matrix
metalloproteinase (MMP-9) Gelatinase B is capable of destroying the
blood-brain barrier, and of cleaving myelin basic protein into
immunodominant and encephalitogenic fragments, thus playing a functional
role and being a therapeutic target in multiple sclerosis. Here we
demonstrate that gelatinase B(MMP-9) proteolytically cleaves IFN-beta, kills its
activity, and hence counteracts this cytokine as an antiviral and
immunotherapeutic agent. This proteolysis is more pronounced with
IFN-beta-1b than with IFN-beta-1a. Furthermore, the tetracycline
minocycline, which has a known blocking effect in experimental autoimmune
encephalomyelitis, an in vivo model of acute inflammation in multiple
sclerosis, and other MMP inhibitors prevent the in vitro degradation of
IFN-beta by gelatinase B(MMP-9). These data provide a novel mechanism and rationale
for the inhibition of gelatinase B(MMP-9) in diseases in which IFN-beta has a
beneficial effect. The combination of gelatinase B(MMP-9) inhibitors with better
and lower pharmacological formulations of IFN-beta may reduce the
side-effects of treatment with IFN-beta, and is therefore proposed for
multiple sclerosis therapy and the immunotherapy of viral infections.
PMID: 12764058 [PubMed - indexed for MEDLINE]
The real sad part for MS folks is that just before and during an MS attack MMP-9s are elevated!!!
1: Mult Scler 2002 May;8(3):222-8
Intrathecal synthesis of matrix metalloproteinase-9 in patients with multiple
sclerosis: implication for pathogenesis.
Liuzzi GM, Trojano M, Fanelli M, Avolio C, Fasano A, Livrea P, Riccio P.
Department of Biochemistry and Molecular Biology, University of Bari, Italy.
Matrix metalloproteinase-9 (MMP-9) was detected by zymography and enzyme-linked
immunosorbent assay (ELISA) in matched serum and cerebrospinal fluid (CSF)
samples from patients with neurological diseases. Patients with
relapsing-remitting multiple sclerosis (RR-MS) had serum and CSF MMP-9 levels
comparable to those from patients with inflammatory neurological diseases
(INDs), but higher than patients with non-inflammatory neurological diseases
(NINDs) and healthy donors (HDs). MMP-9 increased in active RR-MS in comparison
with inactive RR-MS implying that MMP-9 in MS is related with clinical disease
activity. A correlation between the CSF/serum albumin (Q(AIb)) and CSF/serum
MMP-9 (Q(MMP-9)) was observed in IND and NIND but not in RR-MS patients,
indicating that CSF MMP-9 levels in NIND and IND patents could be influenced by
serum MMP-9 and blood-brain barrier (BBB) permeability properties. MS patients
had higher values of Q(MMP-9):Q(Alb)(MMP-9 index) than IND and NIND patients
suggesting that in MS the increase in CSF MMP-9 could be due to intrathecal
synthesis of MMP-9. A significant inverse correlation was found between MMP-9
and its endogenous inhibitor TIMP-1 in RR-MS indicating that in MS patients both
the increase in MMP-9 and the decrease in TIMP-1 serum levels could contribute
to BBB disruption and T-lymphocyte entry into the CNS.
PMID: 12120694 [PubMed - in process]
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Last edited by Chemar; 06-20-2008 at 02:56 PM.
Reason: adding quote tags for referenced abstracts
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