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A Beautiful New Model For MS
05 Sep 2006

Multiple sclerosis (MS) is a disease that affects the cells of the brain and spinal cord. MS can cause various symptoms, including depression, pain, and impaired mobility. Although it is clear that MS is caused by cells of the immune system inappropriately attacking the cells of the brain and spinal cord, much remains unknown about the disease. For example, what triggers the immune cells to attack; what is the identity of the attacking cell(s); and what determines which part of the brain is attacked? Answering these questions has been hampered by the lack of a suitable animal model of MS.

Now, a good, new mouse model of a form of MS -- known both as neuromyelitis optica (NMO) and Devic disease -- that only affects eyesight, limb movement, and bladder and bowel control is described in two independent papers to be published in the September issue of the Journal of Clinical Investigation. Analysis of these mice indicated that disease was caused by cooperation between two types of immune cell known as B cells and T cells. The independent development of this mouse model of NMO by Andreas Holz and colleagues from the Max Planck Institute for Neurobiology in Germany and Vijay Kuchroo and colleagues from Brigham and Women's Hospital in Boston should enable researchers to get more of a handle on the causes of both NMO and MS, thereby providing new avenues of research for the design of therapeutics to treat these debilitating diseases.

In an accompanying commentary, Richard Ransohoff from the Cleveland Clinic, Ohio, discusses why he believes that the mouse model of NMO developed by these two groups will in fact yield more insight into the mechanisms of MS than the mechanisms of NMO.

TITLE: Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperation

http://www.jci.org/cgi/content/full/116/9/2313

http://www.jci.org/cgi/content/full/116/9/2385

Thanks Scooby and Batpere—

I can’t say that I really understand the details of the wonders of this new mouse but on the surface it seems to me that this “new mouse” is still focused on the “auto” immune system and white matter damage. I thought at least some MS research was rapidly moving beyond that.

A sampling of that research:
Etiopathogeny of MS

However, it appears, on the basis of recent findings, that multiple sclerosis is not only a disease of the immune system but also implies specific neurobiological factors which must be determined in studies to come.

MT MRI Metrics Predict Accumulation of Disability Eight Years Later in People with MS

This study also suggests that GM damage is one of the key factors associated with disability accumulation in this 'white matter' condition.

Another abstract notes

These findings suggest that gray matter loss is related to other aspects of brain pathology and has more clinical relevance than white matter atrophy in MS.

The Contribution of Demyelination to Axonal Loss in MS

Our results indicate that plaque load did not correlate with brain weight. Unexpectedly, after adjusting for sex, age and duration of disease, correlations between total plaque load and axonal loss in both the corticospinal tract and sensory tracts were weak or absent at each level investigated. Since there was little correlation between plaque load and axonal loss, the possibility that demyelination is not the primary determinant of spinal cord axonal loss warrants consideration.

Pathology and Definition of MS

During the relapsing-remitting phase, focal lesions are at the forefront of the pathological abnormalities.

During the progressive phase, be it secondary or primary, macroscopic atrophy and axonal loss, the main explanation of the irreversible neurological disability and the expression of the diffuse, chronic and progressive degeneration of the CNS, are emerging to the first place.

As for autoimmunisation which leads to the selective destruction of myelin, is it primary or secondary to an oligodendrocytic apoptotic process?

Now, we’ve discussed the above question and whether or not MS is “auto-immune” with respect to myelin damage several times. Damage to neurons is another question and here’s one perspective on that sequence.

Neuronal Cell Injury Precedes Brain Atrophy in MS

Enough I know. That's just some of the info I've used to form my opinion they will probably need to find an even better mouse model than the one they described. I hope they get on with it too.

Sharon

Sharon,

I have to agree with you in wondering just why some researchers continue to be fixated on the immune system when it comes to MS.

Although it is clear that MS is caused by cells of the immune system inappropriately attacking the cells of the brain and spinal cord, much remains unknown about the disease

When I read comments like this which supposedly were written by the Max Planck Institute researchers, I scratch my head!! I didn't realize that these people had determined the clear cause of MS! Then when I read that the Cleveland Clinic was involved, I knew not to get too excited about this "new animal model".

Like you said, one would have thought that these people would have gone beyond this level of MS research.

Harry

Hear Hear! Excellant post Sharon well suported and clear.
Tahnk you
marie