*MS Article*Causes of nerve damage in MS explained?

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Cause of nerve fiber damage in multiple sclerosis identified

New information in emerging area of MS research could aid therapy

development

Irvine, Calif., October 16, 2006

Researchers have identified how the body's own immune system

contributes to the nerve fiber damage caused by multiple sclerosis, a

finding that can potentially aid earlier diagnosis and improved

treatment for this chronic disease.

The study reveals how immune system B-cells damage axons during MS

attacks by inhibiting energy production in these nerve fiber cells,

ultimately causing them to degenerate and die. Study results appear in

the Oct. 15 issue of the Journal of Immunology.

B-cell-axon activity is an emerging area of MS research, one that is

changing how scientists and clinicians can look at this disease. In

this study, Dr. Yufen Qin and fellow researchers from UC Irvine's

School of Medicine analyzed spinal fluid and tissue samples from MS

patients to identify substances that stimulate a B-cell immune

response. They noted an increased level of B-cell antibodies on

lesions and in spinal fluid bound to two specific enzymes – GAPDH and TPI.

These two enzymes are essential for efficient energy production. The

researchers believe that the binding of these antibodies to these

enzymes – GAPDH, in particular – may lower the amounts of ATP – the

chemical fuel for cells – available in cells, which eventually can

lead to axon cell degeneration and death. In addition to the

energy-production function, GAPDH is involved with a number of genetic

activities, such as RNA translocation, DNA replication and DNA repair.

Other recent studies have shown that binding of inhibitors to GAPDH

and TPI causes decreased ATP production in neurons, followed by

progressive neuronal degeneration and death. Moreover, patients with

TPI deficiency can develop progressive neurological disorders.

" This research is exciting and potentially important for future

treatments because it identifies new antibodies associated with MS

that can be targeted with emerging therapies, " said Qin, an assistant

professor of neurology. " Significantly, these are the first antibodies

to be identified with axon activity, which is a new area researchers

are exploring in the pathology of MS. "

MS is a chronic central nervous system disease that can cause blurred

vision, poor coordination, slurred speech, numbness, acute fatigue

and, in its most extreme form, blindness and paralysis. Some 400,000

Americans have this disease. Its causes are unknown, and symptoms are

unpredictable and vary greatly in severity.

Much MS research is focused on an autoimmune process in which T-cells

attack and damage myelin, the fatty insulating tissue of axons. These

T-cells do not attack axons themselves; the process of demyelination

interrupts electrical impulses that run through these nerve fibers,

thus causing MS symptoms. Demyelination has been considered the

central feature of MS.

Recently, however, Qin has been among a group of researchers who have

discovered that B-cells too are involved with the autoimmune response

to MS. Instead of targeting myelin, these B-cells attack axons

directly. Axons are the long, slender fibers of a neuron that serve as

the primary transmission lines of the nervous system, and as bundles

they help make up nerves.

Research at UCI and elsewhere has shown that myelin grows back if the

T-cell autoimmune response is turned off, and drugs exist or are in

development to block demyelination. Axons, in turn, repair very

slowly, which implies that B-cell attacks on axons may have a

significant impact on the chronic central nervous system damage caused

by MS.

" Since this area of research is in its early stage, it's important to

understand the process by which these B-cell responses happen, " Qin

said. " Hopefully, by identifying these two crucial enzymes, it will

lead to a greater understanding of MS and lead to more effective

treatments for people who live with this disease. "

Johanna Kolln, Hui-Min Ren, Reng-Rong Da, Yiping Zhang, Dr.

Olek, Dr. Neal Hermanowicz, Lutz G. Hilgenberg, A. and

Dr. Stanley van den Noort of UCI and Edzard Spillner of the University

of Hamburg also worked on the study. The National Multiple Sclerosis

Society and the National Institutes of Health provided funding support.

About the University of California, Irvine: The University of

California, Irvine is a top-ranked university dedicated to research,

scholarship and community service. Founded in 1965, UCI is among the

fastest-growing University of California campuses, with more than

24,000 undergraduate and graduate students and about 1,400 faculty

members. The second-largest employer in dynamic Orange County, UCI

contributes an annual economic impact of $3.3 billion. For more UCI

news, visit www.today.uci.edu.

Television: UCI has a broadcast studio available for live or taped

interviews. For more information, visit www.today.uci.edu/broadcast.

News Radio: UCI maintains on campus an ISDN line for conducting

interviews with its faculty and experts. The use of this line is

available free-of-charge to radio news programs/stations who wish to

interview UCI faculty and experts. Use of the ISDN line is subject to

availability and approval by the university.