More symptoms even on Avonex

jackD · 06-18-2008, 05:17 PM

I regret to tell you this BUT AVONEX takes about 4 to 6 months to fully "kick in" and give you favorable reduction of symptoms.

Also Avonex is not effective during major relapses. I think that starting Avonex during an attack may make things a tad worse for three reasons 1 your hyper-active immune system may react to the Avonex and 2 the stress related to the starting of the shots and three the Avonex symptoms may make you "feel sick".

Most folks do not want to explore how MS progreses but are more concerned about the "ultimate cause of MS" (whatever that is).

I can provide some detail info on this but you I must warn you that it will contain SOME BIG WORDS!!!!

Most MS folks seem to panic and beg me to stop-- so I will ask you to actually request me to continue before I provide the detail info.

I find unless you are really on a QUEST FOR INFO that most MS folks will not even read my info. Almost 100% of this "stuff" comes from NLM-NIH PubMed.

I would give you some GREAT links but I am in the under 10 group..
jackD

P.S. I was on AVONEX for last 10 years. Results VERY GOOD!!

jackD · 06-18-2008, 07:48 PM

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]

starfish · 06-18-2008, 08:00 PM

jackD welcome! I like your journal details. Enjoyed your explanation too. Thank you. It won't be long before you can post urls.

jackD · 06-18-2008, 08:01 PM

Simply put MMPs are a family of about 27 (mmp-1 to MMP-27) enzymes that share a common characteristic function and structure of cutting "THINGS" up into little pieces.

Unfortunately for MS folks they (MMP-9s) like to cut a hole in our BBB Blood Brain Barrier and then enter the brain and cut our myelin into three components that the other hungry characters like to dine on.

They (MMPs) all have a zinc ion tip that allows them to break down hydrogen bonds in tissue thus allows absorption of dead or dying tissue to be reabsorbed or sent via the lymph system to others places to exit out the poop shoot.

The MMP-9s usually have an accompanying regulator protein that is suppose to make sure that it only "eat/cuts up" BAD stuff. This is called a TIMP-1. For NORMAL folks there is a one-to-one ratio of MMP-9 to TIMP-1s.

Sad to say for us MS folks that we have lots of MMP-9s that I call ROGUE MMP-9s that have no accompanying regulating timp-1. Just before and during a MS relapse the total MMP-9s level rise significently(ALSO LOTS OF ROGUE MMP-9s). The first thing they do is cut a BIG hole in our BBB Blood Brain Barrier!! They then enter and do the following...

They just wander around the brain cutting up anything "active" and when they run into an active transmission cable the eat through it, The outside of that cable is called myelin. (a fatty insulating substance)

The advantage of taking an Interferon Beta is that after about 4 to 6 months of starting beta treatment that the ratio of MMP-s to TIMP-1s goes back to the desirable one-to-one ration.

There are NO effective drugs to lower just MMP-9s. Some drugs were developed but they shut them all (all 27) down and killed the host.

Some antibiotics seem to lower MMP-9s quite well but taking those for long periods of time can be equally deadly. Likewise taking some steroids can lower the MMP-9s quite well but can be equally deadly over the long haul.

I have many of the FULL TEXT articles in my Web Storage area but since I am unworthy to tell you how to get there to read them I will just say they are GREAT and have LOTS of neat pics and charts. I will post the short abstracts of them.

jackD

Snoopy · 06-18-2008, 08:08 PM

Hello Jack and welcome to NeuroTalk

I'm glad to see you posting. I have always appreciated your information.

If you have the time and wouldn't mind I would like to see you start a thread about supplements. I liked the information you provided at BT.

jackD · 06-18-2008, 08:20 PM

Here is a rather interesting exchange I had with Ed Hill related to this in Dec 2003.

Quote:

This is Ed Hill to me (jackD)

gonna pour a little skunked beer on this one...sorry.

jackD, you are absolutely right that modulation of MMP-9 in the CNS
helps us greatly.

and noodling TIMP (Tissue Inhibitors of MetalloProteinses) production
thereby correcting the TIMP/MMP imbalance long known to be common to
MSrs is a tempting target.

apologies to those already up on the following.

think MMP as open hand with zinc ion in the palm. the zinc ion when
exposed breaks down certain proteins by busting up weak hydrogen bonds
on contact.

TIMPs might best be seen as a second hand closing over the first,
fingers entwined so blocking contact between the zink ion and other
proteins.

normally, like most other MMPs 9 travels with it's TIMP in tow doing
no harm. there are a few ways to remove the TIMP and activate the
zinc ion. and in some cases, particularly in the MS CNS there aren't
enough TIMPs to go around.

MMP-9 has been shown to cut through the vessel walls of the BBB making
way for immune system elements to get in. and inside the CNS it does
all kinds of damage.

on the other hand...

MMP-9 is a working part of the extracellular matrix. that's the gooey
space between cells. when cells die or eject some garbage, MMP-9 is a
major factor in cutting the junk into nice littel bits and sending 'em
off to the lymphatics.(the "other" circulatory system) from whence
they are shuffled out the poopshoot.

this makes noodling with the matrixins a tad tricky at best. MMP-9 is
also the main cutting tool allowing mensus and ovulation. you didn't
think the eggs just pop up on their own did you? that's a whole
article in itself.

i've written here 'bout this in days of yore.

it might just be the reason for women being struck more frequently by autoimmunity.

their whole MMP regulatory system is flipped over and rebooted every
month. that's a risky biz in my book.

anyways...

oncologists have been fiddling with MMP-9 among others because they
facilitate tumor vascularization. arthritis aka rheumatologists have
also done some great work in this area.

the catch?

THE SIDE EFFECTS SUCK!!!!

it's kind of like shutting down garbage collections because the trucks
smell bad.

great fer a few days. but soon the garbage piles up and it's not very pretty.

regards
ed

MORE FORMAL STATEMENT OF THE SAME STUFF

Quote:

1: Neuroscientist 2002 Dec;8(6):586-95

Matrix metalloproteinases and neuroinflammation in multiple sclerosis.

Rosenberg GA.

Department of Neurology, University of New Mexico Health Sciences Center,
Albuquerque, New Mexico 87131, USA.

Matrix metalloproteinases (MMPs) are extracellular matrix remodeling neutral
proteases that are important in normal development, angiogenesis, wound repair,
and a wide range of pathological processes.Growing evidence supports a key role
of the MMPs in many neuroinflammatory conditions, including meningitis,
encephalitis, brain tumors, cerebral ischemia, Guillain-Barre, and multiple
sclerosis (MS).
The MMPs attack the basal lamina macromolecules that line the
blood vessels, opening the blood-brain barrier (BBB). They contribute to the
remodeling of the blood vessels that causes hyalinosis and gliosis, and they
attack myelin. During the acute inflammatory phase of MS, they are involved in
the injury to the blood vessels and may be important in the disruption of the
myelin sheath and axons. Normally under tight regulation, excessive proteolytic
activity is detected in the blood and cerebrospinal fluid in patients with acute
MS. Because they are induced in immunologic and nonimmunologic forms of
demyelination, they act as a final common pathway to exert a "bystander" effect.

Agents that block the action of the MMPs have been shown to reduce the damage to
the BBB and lead to symptomatic improvement in several animal models of
neuroinflammatory diseases, including experimental allergic encephalomyelitis.

Such agents may eventually be useful in the control of excessive proteolysis
that contributes to the pathology of MS and other neuroinflammatory conditions.

PMID: 12467380 [PubMed - in process]

: Semin Cell Dev Biol. 2008 Feb;19(1):42-51. Epub 2007 Jun 19.

MMPs in the central nervous system: where the good guys go bad.

Agrawal SM, Lau L, Yong VW.
Hotchkiss Brain Institute and the Department of Clinical Neuroscience, University of Calgary, Calgary, Alberta, Canada.

Matrix metalloproteinases (MMPs) are expressed in the developing, healthy adult and diseased CNS. We emphasize the regulation of neurogenesis and oligodendrogenesis by MMPs during CNS development, and highlight physiological roles of MMPs in the healthy adult CNS, such as in synaptic plasticity, learning and memory.

Nonetheless, MMPs as "the good guys" go bad in neurological conditions, likely aided by the sudden and massive upregulation of several MMP members.

We stress the necessity of drawing a fine balance in the treatment of neurological diseases, and we suggest that MMP inhibitors do have therapeutic potential early after CNS injury.

PMID: 17646116 [PubMed - indexed for MEDLINE]

Curious · 06-18-2008, 08:36 PM

i'm sorry you do not like our policies and guidlines jack. ones you agreed to when you joined.

we provide a forum, unlike many others where you don't see porn and other spam.

having to actually particapate with only 10 posts isn't much. it does keep people from joining just to post links.

jackD · 06-18-2008, 09:20 PM

Quote:

Originally Posted by Curious

i'm sorry you do not like our policies and guidlines jack. ones you agreed to when you joined.

we provide a forum, unlike many others where you don't see porn and other spam.

having to actually particapate with only 10 posts isn't much. it does keep people from joining just to post links.

Thanks to ALL for saying hello and welcome. I know I will make the 10 post qualification however it did take me 2,756 posts on Braintalk before I was banned as jackD. I hope to make it to at least 3,000 here. I was reborn again as Braindead on Braintalk. I now have 338 posts as Braindead.

jackD AKA Braindead

Jack N Dalton

Curious · 06-18-2008, 10:45 PM

amn is over 5000, you should be safe.

she does bribe the mods.

heck..i'm over 9000 and doc still puts up with me.

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