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Multiple Sclerosis, Alzheimer's and Parkinson's

" SFN: Blocking Proteins Could Help Modulate=20

Multiple Sclerosis, Alzheimer's and Parkinson's "

By Glynn NEW ORLEANS, LA -- November 17,=20

2003 -- Understanding the signals to turn on=20

specific genes in the brain with proteins might=20

enable the modulation of an immune attack to the=20

brain like that of Multiple Sclerosis (MS),=20

according to a study presented here November 8th=20

at the Society for Neuroscience 33rd Annual=20

Meeting. J Crocker, PhD, Department of=20

Neuropharmacology, Scripps Research Institute, La=20

Jolla, California, presented the study. Dr.=20

Crocker's lab is funded by the National Multiple=20

Sclerosis Society, and focuses on the study of a=20

family of enzymes called metalloproteinases.=20

These enzymes are important because they are=20

released by human immune cells, and allow attacks=20

on the brain, leading to diseases such as MS,=20

Alzheimer's and Parkinson's. What the researchers=20

found in this study was that the brain responded=20

to an immune attack by producing an expression of=20

other proteins, called Tissue Inhibitors of=20

Metalloproteinase (TIMPs), or endogenous tissue=20

inhibitors. " The brain responds by trying to=20

prevent these genes, " Dr. Crocker explained. The=20

purpose of this study was to discover and try to=20

work out what specific signals the brain was=20

using to turn on the protective response. " What=20

we found was that the non-neuronal cells in the=20

brain -- microglia and astrocytes -- only respond=20

to very specific chemical messengers related to=20

inflammation, " said Dr. Crocker. " By=20

understanding which signals are required to turn=20

on these specific genes, we might therein be able=20

to modulate the degree and severity of an immune=20

attack to the brain like MS. " This finding could=20

apply to all similar attacks on the brain,=20

including Alzheimer's and Parkinson's. " It is=20

quite clear that these may be important=20

regulators of [brain] injury related to the=20

immune system, " he said. Future therapy might=20

include blocking these enzymes, reducing the=20

injury to the brain, or enhancing the brain's=20

ability to produce these proteins. " [One] might=20

be able to provide a superior therapeutic=20

strategy, " Dr. Crocker noted. Beta-interferon is=20

now provided to MS patients for treatment, but=20

some research shows it has no direct on=20

expression, Dr. Crocker indicated. It may be=20

regulating the enzymes on the other side of the=20

equation. " While we are in our infancy in=20

understanding these proteins in the brain, it's=20

clear from our work, and [from that of] others=20

looking at neurodegenerative conditions, that=20

these proteins clearly have a great deal of=20

potential. " The brain was once viewed as an=20

" immune privileged area, " protected by the " blood=20

brain barrier, " said Dr. Crocker. " That's clearly=20

no longer the case. Inflammation is the=20

ubiquitous feature of neurodegenerative=20

conditions. From Parkinson's to MS, these=20

proteins may play a role in all of them. " Dr.=20

Crocker indicated that the idea of tweaking the=20

immune system is getting a lot of attention in=20

the drug industry. " It's on the horizon, " he=20

said. " How we might be able to train [these=20

proteins] to work for us, instead of against=20

[us], is what's going to come next. " [study=20

Title: Cell-and Agonist-Specific Regulation of=20

MMP and TIMP Gene Expression in Cultured Glial=20

Cells. Abstract 105.5]

------------------------------

Date: Tue, 18 Nov 2003 17:42:39 -0500

From: Irwin Mortman <irwin@...>

Subject: Research News - The World of Multiple Sclerosis

Posting of the following article has been approved by The World of

Multiple Sclerosis http://www.ifmss.org.uk/default.htm

WORLD OF MS UPDATE SERVICE, 18 November 2003

Research News

====================

The interleukin-1 gene family in multiple sclerosis susceptibility and

disease course

--------------------

The authors found no associations between the interleukin-1 gene

polymorphisms and susceptibility to MS or clinical features. There

was no

significant effect of the polymorphisms on brain or lesion volumes,

suggesting that there is no evidence to support a role for

interleukin-1

genes in MS.

http://www.msif.org/go.rm?id=10796

Blood-brain barrier disruption in multiple sclerosis

--------------------

Dysregulation of the blood-brain barrier (BBB) and transendothelial

migration of activated leukocytes are among the earliest

cerebrovascular

abnormalities seen in MS. In this review the authors examine the

interactions between cytokines/chemokines, activated leukocytes,

adhesion

molecules and activated cerebral endothelial cells in the

pathogenesis of

BBB failure in MS.

http://www.msif.org/go.rm?id=10797

Co-occurrence of multiple sclerosis and myasthenia gravis in British

Columbia

--------------------

The authors report 8 cases with associated multiple sclerosis and

myasthenia gravis, providing further evidence for a nonrandom

association

of these two diseases.

http://www.msif.org/go.rm?id=10798

MRI/MRS of corpus callosum in patients with clinically isolated

syndrome

suggestive of multiple sclerosis

--------------------

No atrophy of the corpus callosum was observed in 46 patients with

clinically isolated syndrome suggestive of MS, whilst decreased

magnetization transfer ratio, increased mean diffusivity and increased

Choline were found. These findings suggest the presence of myelin

pathology

of the corpus callosum at the earliest stage of MS, before any

atrophy is

detected.

http://www.msif.org/go.rm?id=10799

Disability in multiple sclerosis is related to normal appearing brain

tissue MTR histogram abnormalities

--------------------

There is evidence of diffuse magnetization transfer ratio

abnormalities in

normal-appearing brain tissue (NABT), in addition to global brain

atrophy,

in 95 relapse onset MS patients, including those with recently

diagnosed

RRMS and benign MS. These abnormalities are greatest in patients with

the

more disabling SPMS. Atrophy, NABT and lesion abnormalities are all

partly

correlated.

http://www.msif.org/go.rm?id=10800

Phosphodiesterase inhibitors suppress IL-12 production with microglia

and T

helper 1 development

--------------------

Phosphodiesterase inhibitors significantly suppressed the interleukin-

12

production and may also suppress differentiation of T helper 1 in the

central nervous system, suggesting that they can be of use for future

therapeutic strategy in multiple sclerosis.

http://www.msif.org/go.rm?id=10801

Cytapheresis with a filter for selective removal of CD4+ T cells in

experimental autoimmune encephalomyelitis

--------------------

The authors performed a depletion of CD4+ T cells from the systemic

circulation by extracorporeal treatment in experimental autoimmune

encephalomyelitis (EAE). Results were encouraging and suggested a

potentially useful strategy for treatment of acute phase and

relapsing MS.

http://www.msif.org/go.rm?id=10802

Whole-brain atrophy in multiple sclerosis measured by two segmentation

processes from various MRI sequences.

--------------------

Brain parenchymal fraction, a normalized measure of whole-brain

atrophy, is

affected by both pulse sequence and segmentation method. Automated

measurement has high reproducibility especially when 2D sequences are

used.

Semi-automated measurement may have increased accuracy, but with a

decreased efficiency and reliability.

http://www.msif.org/go.rm?id=10803

Immune parameters associated with early treatment effects of high-dose

intravenous methylprednisolone in multiple sclerosis.

--------------------

The authors analyzed lymphocyte subsets and humoral immune parameters

in

peripheral blood and cerebrospinal fluid (CSF), before and within 2

weeks

of treatment during 19 relapses in 16 relapsing-remitting MS patients.

Early clinical improvement was significantly associated with a

decrease in

CSF CD4(+)CD29(+) helper inducer T cells, whereas they were nearly

unchanged in four patients who showed no improvement. Changes in other

parameters were not different between responders and non-responders.

http://www.msif.org/go.rm?id=10804

A longitudinal study of quality of life and side effects in patients

with

multiple sclerosis treated with interferon beta-1a.

--------------------

In a 12-month follow-up study, the authors evaluated 27 patients with

relapsing-remitting MS, who had started treatment with interferon

beta-1a

(Avonex), 30 microg i.m. once a week. Results showed that IFNbeta-1a

did

not significantly change patient's quality of life. Side effects,

which

were mild, did not diminish over time, did not induce treatment

discontinuation and did not interfere with quality of life.

http://www.msif.org/go.rm?id=10805

Trends in prevalence and incidence of multiple sclerosis in Bajo

Aragon,

Spain.

--------------------

An increased prevalence of MS in the area of Bajo Aragon, northeastern

Spain, has been calculated between 1994 and 2002. This increased

prevalence

is more likely to be due to improvement on case ascertainment than to

increasing incidence. However, further prospective incidence studies

in

larger populations are warranted.

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Hmmmmmmmm....although not mentioned, doesn't this and credance to

LDN?

> Multiple Sclerosis, Alzheimer's and Parkinson's

> " SFN: Blocking Proteins Could Help Modulate=20

> Multiple Sclerosis, Alzheimer's and Parkinson's "

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