Maximizing INTERFERON-Beta effectiveness

A board to discuss the Multiple Sclerosis modifying drug Avonex

Re: Maximizing INTERFERON-Beta effectiveness

Postby jackD » Wed Apr 04, 2012 3:43 pm

This is only for the truely preverted(sic)!!!



This link is the CYTOKINES lovers playground. The above link will show you everything you ever wanted to know about MMP-9s.



It is here that I discovered that Good Old Vitamin D3 is a POTENT producer of NGF - Nerve Growth Factor, which is GREAT stuff for those small brain(pun intended) repair jobs that MS folks frequently need performed. (TAKE A LOOK - IT REALLY DOES NOT HURT FOR LONG) (Interferon Beta INFO)

P.S. Please keep this a SECRET ---"COPE (Cytokines & Cells Online Pathfinder Encyclopedia) is NOT in the public domain!"
Last edited by jackD on Sun Feb 02, 2014 12:27 pm, edited 4 times in total.
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Re: Maximizing INTERFERON-Beta effectiveness

Postby jackD » Wed Jan 29, 2014 5:26 pm

I am really surprised by the lack of comments on this post. It seems to be essential info for Avonex folks.

I also took Valtrex as part of my MS program because my MS seemed to be caused as a consequence of a series of common viral infections.

My posting here may be a bit technical but that is the nature of the MS mystery disease.

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Re: Maximizing INTERFERON-Beta effectiveness

Postby jackD » Sun Feb 02, 2014 10:40 am

We may not know what causes MS but a LOT is known about the FINAL step in myelin damage - the actions of the destructive MMPs(i.e. MMP-9). (SEE FIGURE 2 page 505_)


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

Matrix metalloproteinases and neuroinflammation in multiple sclerosis.

Rosenberg GA.

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]

MMPs are a family of 20+ members that comprise 4 major groups differing
in protein structure and substrate specificity. The major MMPs in the
brain include gelatinase A (MMP-2), stromelysin (MMP-3), matrilysin
(MMP-7), gelatinase B (MMP-9) and membrane-type metalloproteinases.
MMP-2 and MMP-9 attack the basal lamina around the blood vessels,
altering the permeability. MMP-2 is a constitutive enzyme normally
found in the CSF. MMP-9, which is induced during the neuroinflammatory
response, is increased in the CSF of MS patients with
gadolinium-enhancing lesions on MRI. Treatment with high-dose steroids
returned the MMP-9 levels to normal. In contrast, patients with
Devics neuromyelitis optica had no elevations of CSF MMP-9. MS
patient subanalysis disclosed significant differences in MMP-9 CSF
levels in relapsing/remitting (RR) and in secondary progressive (SP)
MS patients. CSF-MMP-9 levels were markedly elevated in RR, but not in
SP cases. In patients with RR disorder, CSF levels of
tissue-inhibitors of metalloproteinases (TIMP-1) were decreased,
whereas in patients with SP disease these levels were normal, as in
patients with Devics syndrome. These results suggest an excess
of MMP-related proteolytic activity in brains of patients with MS.
MMPs are produced by all cell types in the brain, including neurons,
glia and invading leucocytes and macrophages. The enzymes attack all
components of the extracellular matrix, and participate in the opening
of the BBB by disrupting the basal lamina around the blood vessels.10

IFN-beta blocks the activation of MMP-9, and is synergistic with the
action of high-dose steroids. IFN-beta-1a supressed MMP-9 and MMP-7
mRNA in R/R patients, but not in SP patients, as predicted from the
previous study. The IFNbeta mediated decrease in MMP-9 expression may
contribute to suppressed migratory capacity and reduced transavasation
of immune cells into the CNS. In vitro data has demonstrated that
exposing activated T cells to IFN-beta resulted in a significant
decrease in MMP-9 expression associated with inhibited T-cell
migratory capacity, likely at the transcriptional level, or through
expression of lymphokines or chemokines.

Changes in MMP and TIMP correlated with clinical reduction of disease activity induced by
IFN-beta. A shift in the MMP/TIMP ratio from a
pro-proteolytic toward an anti-proteolytic
profile appears to occur with IFN-beta-1A. This shift occurs in
parallel to the IFN-beta-mediated cytokine deviation from Th1 to Th2
profile. The inhibition of MMP-s proteolytic activities resulting from
IFN-beta1 treatments may decrease the autoimune cells
migratory capacity and the invasiveness through the BBB into the CNS,
and reduce MMPs mediated damage to myelin.
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Re: Maximizing INTERFERON-Beta effectiveness

Postby jackD » Fri Feb 14, 2014 6:58 pm

Once the Myelin is removed then the NEXT BAD thing happens - AXONAL TRANSECTION - BIG TIME!!!


N Engl J Med. 1998 Jan 29;338(5):278-85.

Axonal transection in the lesions of multiple sclerosis.

Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L.


Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system and is the most common cause of neurologic disability in young adults. Despite antiinflammatory or immunosuppressive therapy, most patients have progressive neurologic deterioration that may reflect axonal loss. We conducted pathological studies of brain tissues to define the changes in axons in patients with multiple sclerosis.


Brain tissue was obtained at autopsy from 11 patients with multiple sclerosis and 4 subjects without brain disease. Fourteen active multiple-sclerosis lesions, 33 chronic active lesions, and samples of normal-appearing white matter were examined for demyelination, inflammation, and axonal pathologic changes by immunohistochemistry and confocal microscopy. Axonal transection, identified by the presence of terminal axonal ovoids, was detected in all 47 lesions and quantified in 18 lesions.


Transected axons were a consistent feature of the lesions of multiple sclerosis, and their frequency was related to the degree of inflammation within the lesion. The number of transected axons per cubic millimeter of tissue averaged 11,236 in active lesions, 3138 at the hypocellular edges of chronic active lesions, 875 in the hypocellular centers of chronic active lesions, and less than 1 in normal-appearing white matter from the control brains.


Transected axons are common in the lesions of multiple sclerosis, and axonal transection may be the pathologic correlate of the irreversible neurologic impairment in this disease.

Comment in
Demyelinating diseases--new pathological insights, new therapeutic targets. [N Engl J Med. 1998]

PMID: 9445407 [PubMed - indexed for MEDLINE] Free full text
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