New information in emerging area of MS research could aid therapy 
development

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. Michael 
Olek, Dr. Neal Hermanowicz, Lutz G. Hilgenberg, Martin A. Smith 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.