Avonex and leg weakness?
 

Is it possible that Avonex may be causing some leg weakness? The Avonex rep said that would most likely be a symptom of MS and not a side effect of Avonex.

It was my right leg that was the main problem before; but now I am having trouble with my left leg.:(

I am just wondering if anyone noticed an increase in any of their symptoms, especially leg weakness and stiffness, after starting their injections.

LA

I've been on it for the past few years and haven't noticed anything like that, beautiful. And if it continues I would definitely quiz my doc on it. Could be the shots, could be MS... could be something else that needs to be addressed. But here's hoping it's nothing major.:)

ABSOLUTELY I did. Yep. Honestly, sometime within 3 weeks of starting the avonex injections, I experienced gait problems ...best described as unsteadiness. I lost confidence in my ability to balance and be agile.

I called my neuro at that time, and also my injection nurse from biogen and they both told me it was very common to experience a subtle worsening of symptoms after beginning Avonex therapy. They also told me - WITH conviction - that the worsening of symptoms was temporary and would subside. ...and it did.

When I was on Avonex, I never had anything like that....a couple of times I felt extra extra tired....

I will be taking mhy 3rd dose in about an hour. :( I wish I could take the shot every two weeks.

For the frist two weeks so far I feel pretty good on Wednesday and Thursday then I start all over on Friday.

I will be taking 3/4 dose tonight. I am having some symptoms I didn't have before. But I am also feeling just a bit better in between.

I wonder if that is because of the Trileptal though. I think we could spend our whole life trying to figure this MS stuff out and never make a dent.

LA

I actually did have a problem with leg weakness and stiffness when I took Avonex, along with nasty joint and muscle pain. Sometimes it's hard to tell what's causing the symptoms but I do remember in the beginning the side effects from the shots were much worse until my body became somewhat adjusted to the med.

Hang in there and if it continues, you might want to run it by your doc.

I was basically asymptomatic and had no treatment for 9 years. During pregnancy, my feet were tingling and continued to do so after my baby was born. My neurologist suggested that I start injections - I was very reluctant. After much consideration, I decided to try Copaxone. I had horrible reactions to it so I was switched to Avonex. I have gone from being asymptomatic and very active to having leg weakness, loss of balance, incontinence, and general weakness since beginning treatment. Treatment was supposed to delay relapses (of which I hadn't had one in 9 years). I think I was much better off when I didn't take any medication but, of course, my neurologist disagrees that the treatment could be causing a change in my disease. I am looking for information from anyone that has also had worsening of symptoms since starting Avonex.

Wow, this is an old post from March! I am not having leg weakness after my injection any more.

I took shot number 35 this past week in my arm. :D

LA

OH, no my 35th injection was actually my first shot in my arm. I am having a difficult time putting it into my legs. My muscle tightens up and I have to push harder. :eek:

I decided to try my arm this time and it went much better! I am on Avonex too.

I can't stand the thought of that needle going into my arm (or other sites)...:eek:

I know some people say that their thigh does not bother them. Actually the worst place I can think of would be my hip. That is because I had to have a lot of injections in my back side when I was little.

Whatever works is where ya got to go! :D

Maximize Avonex by lower MMP-9 levels
 

You need to get the most potent protection from Avonex(any Beta) by preventing its destruction by those nasty MMP-9s.

If you want to maximize Avonex (or any beta interferon), lowering MMP-9s will prevent it from being degraded by being cleaved into parts thus killing its Activity/Effectiveness.

http://www.cnsforum.com/commentedite...9/default.aspx

Also getting the most activity from the least amount of near natural (human) interferon like Avonex will usually result in MUCH LESS neutralizing antibody formation (2-5% vrs 20-26%).

Unfortunately for MS folks (MMP-9s) also 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. This mechanism of destruction caused by excessive agressive MMP-9s is a good target for reduction and should reduce MS damage if lowered a tad. Actual abstracts and one major study on my web page are provided below.

http://home.ix.netcom.com/~jdalton/Yongrev.pdf

SEE FIGURE 2 and MS info on page 505


Things that reduce MMP-9s (AKA gelatinase B)

This list of GOOD "things" for MS should seem familiar - This is WHY???

VIT D3 .................................REDUCES MMP-9s

RESVERATROL (Grape Skin Extract) ...REDUCES MMP-9s
(NOT GRAPE SEED EXTRACT)

GREEN TEA EXTRACT(EGCGs)... REDUCES MMP-9s

ALPHA LIPOIC ACID (R-lipoic/ R-Dihdro-LipoicAcid) ... REDUCES MMP-9s

NAC N-Acetyl-L-Cysteine .......REDUCES MMP-9s

STATIN DRUGS (i.e Zocor) .....REDUCES MMP-9s

Omega-3s (ie Fish oil) ...........REDUCES MMP-9s

Minocycline/Doxycycline.........REDUCES MMP-9s

Curcumin.............................REDUCES MMP-9s

Pycnogenol (Pine bark extract)..REDUCES MMP-9s

QUERCETIN..........................REDUCES MMP-9s

Chondroitin sulfate (CS) and CS plus glucosamine sulfate (GS) ..REDUCES MMP-9s

Interferon Betas 1a/1b...........REDUCES MMP-9

(of course Steroids ....REDUCES MMP-9s)

***NOTE*** ( gelatinase B = MMP-9) ***NOTE***


I have lots more information on this MMP - MS - INTERFERON-beta connection and will elaborate it if there is some interest in this subject here.

jackD


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]


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-Barré, 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 - indexed for MEDLINE]

Strange as it may seem DRUGS so far have not been found that lower MMPs without killing folks. However SUPPLEMENTS seem to do the job and provide GOOD Genaer health improvements. Check out this abstract from LEABANON on role of MMPs in rheumatoid arthritis (RA) and osteoarthritis (OA).

jackD

1: Front Biosci. 2006 Jan 1;11:529-43.

Matrix metalloproteinases: role in arthritis.

Burrage PS, Mix KS, Brinckerhoff CE.
Department of Biochemistry, Dartmouth Medical School, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA.

The irreversible destruction of the cartilage, tendon, and bone that comprise synovial joints is the hallmark of both rheumatoid arthritis (RA) and osteoarthritis (OA). While cartilage is made up of proteoglycans and type II collagen, tendon and bone are composed primarily of type I collagen. RA is an autoimmune disease afflicting numerous joints throughout the body; in contrast, OA develops in a small number of joints, usually resulting from chronic overuse or injury.

In both diseases, inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) stimulate the production of matrix metalloproteinases (MMPs), enzymes that can degrade all components of the extracellular matrix. The collagenases, MMP-1 and MMP-13, have predominant roles in RA and OA because they are rate limiting in the process of collagen degradation. MMP-1 is produced primarily by the synovial cells that line the joints, and MMP-13 is a product of the chondrocytes that reside in the cartilage. In addition to collagen, MMP-13 also degrades the proteoglycan molecule, aggrecan, giving it a dual role in matrix destruction.

Expression of other MMPs such as MMP-2, MMP-3 and MMP-9, is also elevated in arthritis and these enzymes degrade non-collagen matrix components of the joints.

Significant effort has been expended in attempts to design effective inhibitors of MMP activity and/or synthesis with the goal of curbing connective tissues destruction within the joints.

To date, however, no effective clinical inhibitors exist.

Increasing our knowledge of the crystal structures of these enzymes and of the signal transduction pathways and molecular mechanisms that control MMP gene expression may provide new opportunities for the development of therapeutics to prevent the joint destruction seen in arthritis.

PMID: 16146751 [PubMed - indexed for MEDLINE]