This Is MS Multiple Sclerosis Community: Knowledge & Support

In recent years it has been recognised that axonal loss is the main cause of permanent disability. The traditional view is that attacks by the immune sytem result in demyelination and that the underlying nerve fibres (axons) degenerate. The damage is considered to take place under the lesions which form where de-myelination has occurred. As with everything connected with this disease - nothing is straightforward. Attached is an article which suggestes that demyelination and axonal loss are not necessarily linked. One of the authors is Professor Esiri and I have been following her work for some time. She is funded by the UK MS Society to study the damage caused by MS and its cause. I think this research may well turn out to be a turning point. It might be that axonal damage / loss occurs before the immune response. It's not comfortable reading but the sooner the researchers get a better understanding of what is happening and why, the sooner they can identify ways to address the problem.

Ian


http://www.msif.org/en/research/researc ... ution.html

Great Paper thanks for posting it. If you go to that paper and click the link called related articles in the upper right corner, you get a list of other older material talking about axon loss compared to myelin/lesion load and it all is saying much the same thing. Sadly this is less "new" than it seems....
It dovetails nicely with Prineas and Barnett's paper though. If the nerves die then the immune system comes in what other damage might occur? IT is known that things in the periphery which would damage myelin are kept out by the bbb, and according to my neurologist this includes myelin active antibodies which are molecular mimics. He said everyone has myelin active antibodies in their blood ( I was asking why we can't test for the myelin active antibodies), the problem is most people keep them out of their brains.

The bbb can be opened on purpose by activated microglia, say if a cell dies, in order to have peripheral monocytes t-cells etc in to clean up .

warning speculation: maybe the nerves die as suggested by P&B, the microglia activate and open the BBB, peripheral immune cells enter, and bring with them accidentally these molecular mimics that damage the myelin, causing a secondary myelin issue. Kind of like if you get a cold you might get an earache secondary. And interestingly did you know that b-cells are often infected with EBV and carry it in to where they go? I stumbled into this in the RA world. There is high levels of ebv in RA joints but it is thught to be secondary to b-cell presence not the primary cause of the joint problem.

Speculation and more speculation! God I wish there was more solved/
I certainly hope it is a good year for MS!
Marie

Marie,

The real breakthrough will come when the experts work out the chain of events. The B cell angle is very interesting as Rituximab reduces the number of B cells (being trialled in PP, SP and RR). The drug has also recently been approved for RA has it has shown good results for RA cases where other drugs did not.

All the best

Ian

Ian,

Thanks for that very interesting article.

I think that many comments have been made that demyelination is a reaction by the immune system to something else far more destructive going on when it comes to MS. Yet we all know where the vast majority of MS research continues to center around....more powerful immune system altering drugs that try and prevent this secondary action.

I fear that unless this line of research changes, the real culprit isn't going to be discovered for quite some time.

Harry

Ian

Welcome back....I'm fascinated by this research on axonal loss and whether or not it's related to demyelination. I think you're absolutely right that once they know the injury cascade we're much closer to better interventions.

Here are some abstracts about axonal loss that may, or, as the case may be when you have no medical or scientific background, may not be related.

Inside Out vs. Outside In Models of Virus Induced Demyelination: Axonal Damage Triggering Demyelination


The same researchers later reported: Axonal injury heralds virus induced demyelination


And, lastly, there's this. Axonal loss in normal-appearing white matter in a patient with acute MS

The "inside out" model of axonal loss actually makes some sense to me on the surface. It could help explain (or so it seems) why men (with that thicker myelin from testosterone ) generally have less inflammation than women and tend to be diagnosed at a later age.

This same research group has also found a relationship with COX-2 in a model of viral induced demyelination. Pathological Role for COX-2
Hopefully some line of research will make 2006 a very good year for MS. I'm optimistic progress is being made.

Sharon

Thanks Sharon,

Dr Esiri's work is due to report in June - she is a neuropathologist.
I imagine that we will also see another instalment in the Lesion Project overseen by Dr Luccinetti.

The inside v outside issue seems to be key. MS, or some forms of it, may be like a car rusting from the inside and every now and then some paint flakes off. Patching up the area where the paint flakes off will never address the undelying problem.

I do see a shift in the research. The recent research on Testosterone talks about tissue loss rather than myelin. But there's an industry focussed on the myelin / auto-immune theory and it will take time to shift them.

Ian