Immune system

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Immune system

Postby bromley » Tue Aug 22, 2006 3:22 am

Dear all,

Here is an easy to read intro about the immune system and MS - with some nice pictures.

Ian

http://www.nationalmssociety.org/IMSAug ... nflict.asp
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What Kind of Disease is MS?

Postby Shayk » Tue Aug 22, 2006 5:31 pm

Hi Ian

While I really appreciate the fact that NMSS piece on the immune system and MS mentions hormones 8) and has pictures, I'm really disappointed that the NMSS discussion of "Inside MS" makes no mention of neurodegeneration and MS. As far as I'm concerned neurodegeneration is also "Inside MS".

Here's an abstract, no photos, but I think it's an understandable read. MRI Evidence for MS as a Diffuse Disease of the CNS
There is now overwhelming evidence supporting the following statements: MS causes widespread tissue damage in the normal-appearing white matter (NAWM) of the brain and spinal cord, whose extent and severity is more strictly associated to the clinical manifestations of the disease than the extent of focal pathology. Discrete, macroscopic lesions are just the tip of the iceberg of MS pathology. Grey matter (GM) damage is a consistent feature of all MS phenotypes, which is progressive from the start of the relapsing-remitting phase of the disease. As is the case for WM, GM damage is also a mixture of focal lesions and diffuse pathology.

The neurodegenerative component of the disease is not a late phenomenon and it is not completely driven by inflammatory demyelination. In fact, neurodegeneration occurs very early in the course of MS and the correlation between MRI measures of inflammation and neurodegeneration is weak in all disease phases.

All of this calls for the concept of MS as a focal, inflammatory demyelinating, WM disease to be reexamined and to start viewing MS as a diffuse CNS disease with an important neurodegenerative component. This is central for identifying novel and effective treatment strategies.


The following presentation from the MS Care Consortium puts an emphasis on MS as a neurodegenerative disease and is somewhat understandable. There are pictures too.Neuroprotection: A Therapeutic Approach for a Progressive Disease

I know the NMSS has a neuroprotection initiative, I just cannot understand why they continue to put almost total emphasis on the "immune system."

I'm glad you're back from vacation. :wink:

Sharon
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Postby bromley » Wed Aug 23, 2006 3:08 am

Sharon,

Neuro-degeneration is the issue that keeps me awake at night.

The existing theory is that axons get de-myelinated by the immune system attacks and begin to degenerate (as they are no longer supported by the myelin). Some re-myelination takes place saving some axons in the RR stage. Eventually, after a period, a sufferer moves into the progressive stage where axons are dying off leading to more and more disability.

So the treatment theory is to focus on the immune attack and in particular inflammation. The CRABs only reduce attacks by 30%, Tysabri by 66%, Campath and Mitoxantrone by 75%ish. In the case of the last two, they appear to provide stabilisation and in some cases reductions in EDSS. So there seems to be some evidence to support the theory that substantiually reducing attacks / inflammation does seem to save axons.

The complication for me is the damage to grey matter - MS was always described as a white matter (myelin) disease. Also PP MS where there are no attacks - axonal degeneration is the main feature from the start.

The question that the researchers have to answer is - Is MS a neuro-degenerative disease and the immune system responds (trying to clean up the damage) OR an inflammatory disease caused by the immune system which leads to neuro-degeneration? This appears to be the key - most research is focussed on the latter. It concerns me that diseases such as Parkinsons and Alzeimers are neuro-degenerative (involving some inflammation) but are not described as auto-immune like MS. But at the end of the day all three result in damage to the brain!

There is much research into neuro-degeneration and neuro-protection. And some neuro-protective drugs are being trialled.

Attached is a link to a UK Professor who is looking at the pathology of MS. She seems to be surprised at the extent of neuro-degeneration in MS. At least the researchers are looking out of the box, but it would be a scandal if the last 50 years of MS research were shown to be a waste of time.

Ian

http://www.mssociety.org.uk/research/re ... esiri.html
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Postby bromley » Wed Aug 23, 2006 4:49 am

Sharon,

Many thanks for copying the presentation on neuro-protection from Yale. Brain atrophy, disability, axonal-dissection etc are terms that I struggle with. On the other hand, progress will only be made when there is a better understanding of the disease and the various processes that underlie it. While relapses / inflammation are, on the whole bad, the good news is that there are drugs currently available and in the pipeline which can substantially reduce these. But it is clear that this might not be enough and neuro-protection is also needed to stop the neuro-degeneration which leads to disability. Treaments which substantially reduce relapses / inflammation / lesions are one part of the strategy and treatments to protect nerve fibres are the other part - and such treatments are not that far off.

Howard Weiner, an MS 'expert', wrote in an article I posted some time ago:

'I believe that in future, MS patients will receive
strong anti-inflammatory therapy right from the start, followed by the
addition of degeneration-blockers. MS could be turned from a
relentlessly progressive disease that causes permanent pain and
disability into a relatively mild condition that can be kept in check
with the right medicines'.

This must be our hope and the combination should prevent or radically slow down progression / disability. Given your age, you may not need a walking stik until you are 122!

Of course, there is also a need to repair the damage done, and stem cells / nerve growth factors etc offer this possibility. I saw an interview with Dr Calabresi from Johns Hopkins, who said that the wanted to "get patients better". Advances in the next few years should make this a reality.

Ian
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Postby Shayk » Wed Aug 23, 2006 5:43 am

Ian

I definitely want to keep the neurodegeneration in check. In terms of future MS research I am personally encouraged by the fact that I think many researchers have in fact "turned the corner" and now recognize the need to contain the neurodegeneration that seems to be part and parcel of MS. That's definite progress IMO. That there are drugs in the pipeline targeting degeneration is also encouraging.

Whether or not I want to live to 122 without needing a walking stick is another question. :roll: I do want to live without needing one, that's for sure.

Take care

Sharon
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Postby bromley » Wed Aug 23, 2006 6:15 am

Sharon,

Much of the NMSS Promise 2010 initiative focuses on neuro-protection and repair.

One of the leading lights in the UK is Professor Ken Smith who is currently overseeing a neuro-protective treatment trial (started in January and runs for two years). Attached is some of the research which shows that the treatment being trialled is very effective at radically slowing the degeneration of axons.

Professor Smith is presenting at ECTRIMS about the treatment trial. If the trial proves successful then an in-expensive and safe oral drug could be ready for prescribing in 2008.

<shortened url>

A bit more on Prof Smith:

<shortened url>

Of course lots of others around the world are looking at other neuro-protective agents e.g. Dr Calabresis is looking at drugs such as EPO. Also, re-mylination should protect axons.

Apologies to those who have seen me post these links before. But things are shifiting quickly in MS research and there is now a recognition that dampening the immune system is not going to be enough.

Ian

The concern about neuro-degeneration is shared by MS researchers across the world. Here are the thoughs of a Canadian MS researcher:

http://www.msanswers.ca/QuestionView.aspx?L=2&QID=35
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