This Is MS Multiple Sclerosis Community: Knowledge & Support

Dear all,

My favourite topic again - neuro-protection. This to me offers the best chance of reducing the risk of, or severity of, disability. However, I suspect that it doesn't offer drugs companies the sorts of returns they can get from the drugs which work (partly) on reducing attacks from the immune system.

It's interesting to see that Copaxone is being trialled with NAC to see whether the two together can offer neuro protection. Dr Hyman Schipper said 'To date, most pre-clinical and clinical studies investigating therapies for MS have focused on the immune-mediated inflammatory stage of the disease. Far less attention has been paid to the management of the simultaneous, neurodegenerative phase of the illness, which is now believed to contribute significantly to irreversible brain tissue damage, clinical disability and brain atrophy in MS patients'.


Most researchers are now recognising that there is more at play than just attacks by the immune system. I have taken a few recent quotes from the UK MS Society website (there's probably many more from other national websites):

Professor George Ebers - What (in your opinion) does the future hold for MS Research? At present we can prevent relapses, in the future we will be able to prevent disability and I think it very likely that there will be a plausible prevention strategy in the next 1-2 years.

Professor Kenneth Smith - Most recently we have tried to understand why nerve fibres degenerate in MS. Once degeneration has occurred, function is likely to be permanently damaged because nerve fibres do not regrow in the brain and spinal cord. It is therefore very important to try to find ways to protect the nerve fibres from degeneration. We have found a potential reason why degeneration occurs, and we have identified an effective therapy to protect the nerve fibres. The therapy appears to work well, and it should be safe and inexpensive, and we are seeking funding to conduct a full clinical trial in MS patients.

Professor Neil Scolding - Drugs causing even the most intense suppression of inflammation do not stop disability progressing in MS. This is probably because other, non-inflammatory mechanisms cause progressive axon loss.


This I believe should give us some real hope - hopefully, in the not too distant future. But things in MS always seem to operat at a snail's pace.


I think it would be worth having a forum on neuro-protection where we can post articles, information on drugs trials etc. I'd certainly be interested in hearing about research projects in this area - is the NMSS funding specific research on this issue? This is one area where national societies should be seeking to fund small trials and perhaps we need to lobby them - let the drugs companies run the trials for the immune system drugs.

What we need to avoid is a system where the drugs companies using their existing immune system drugs add on a possible neuro-protective drug (as Copaxone is doing - and also with minocycline). The trial results will never be broken down to show the effect of each drug separately which means that the two will have to be used / bought as a combo (thereby protecting the companies revenue).


Bromley

Hi, bromley!

As you know, I've been working hard in that very area of MS (axonal regeneration, protection, and neuroprotection).

Yes, the NMSS has a new very large initiative for funding going right now (attempting to get more researchers to become engaged in this area).

Go to: http://www.nationalmssociety.org/Research-Targeted.asp

Then go down and click on "Nervous system repair and protection NEW!"

I have talked with them about HOW in the world we can get researchers engaged in applying for funding in that area. As you know, I am doing my best in that area, also (and at times have met with unbearable frustrations). As I said, though, the NMSS is fully supportive of my research (as one example) and of having it studied further. The extreme difficulty is in getting researchers to become interested in it, also.

We can speculate on "why" they are not more focused on neuro-protection and regeneration........some being conspiracy-driven (such as how much money can you make from your practice if most of your patients keep their MS well-managed via new therapies, etc.), i.e. the "money" aspect; to some just not being knowledgeable enough; to some being hesitant because they are "afraid" they won't get the funding, so they don't even try; etc. etc.

In any event, yes, the NMSS at least IS attempting to get some people focused and engaged in this part of MS research. And as I said, I have been ACTIVELY attempting to help them in this endeavor. So far, to no avail. (And as I said, I haven't been the only one who hasn't succeeded. It's just a bigger shame, because I have a chemical agent that is right here to be tested.)

I'm not sure where to turn myself at this point, bromley.

Deb

The drug companies and many researchers would argue that MS is a T cell mediated auto-immune condition. By going after the inflammatory aspect of the condition they are attempting to control the cause. In this case neuro-protective strategies are secondary measures, possibly to be used in combination.

It is accepted that once the progressive phase is reached there are other mechanisms at work and that anti-inflammatory measures are no longer effective. But if the inflammation can be controlled early enough, can the progressive phase be prevented?

I asked this question of Prof Neil Scolding when I met him (incidentally his stem cell research is funded in part by the UK MS society). His answer was a wry smile followed by 'We just don't know, but if that is the case (i.e. that MS is not primarily an auto-immune condition) then none of the current treatments will be effective in the long term'. He also said that less than 10% of current research / funding is looking away from the auto-immune / inflammatory aspect. It was his opinion that much more effort should be focussed upon other avenues.

It's a hopeless trade off. We all want treatment options now. The only proven aspect of MS is the inflammatory one. Therefore current treatments focus on that area. Until other mechanisms can be proven that situation will not change.

This is where I am fully behind Art and his efforts with the Boston Cure Project. They are attempting to map the causes of MS, reasoning that once the cause is known then curative strategies will become apparent.

Makes sense to me.

Robin

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Do not go gentle into that good night. Rage, rage against the dying of the light.

Hi, Robin! (Doing even better, I hope?)

Yes, I hear you.

The problem (well, maybe that's the wrong word), but another aspect is that the Mayo (as just one example) have been finding out that axonal damage is happening without inflammation being prevelant.

And inflammation is NOT a huge factor in progressive MS. I realize and totally agree with you that the majority of MS can be classified as RRMS, which does show proven evidence of the immune system involvement and much inflammation. The thing is, as you, me and Wesley have discussed before, is whether or not it's the inflammation itself causing the axonal damage? And it's the axonal damage that causes the disability.

(Of course, here we go again, round and round, and our gray matter discussion before - I still say that was a good one! - pretty well covered all our theories, etc. on this.)

Unfortunately, that's still the bottom line, huh? "We just don't know for sure".

I support the combination therapy myself. Do both. Something that keeps the immune system balanced and from "acting up", shall we say, and at the same time protect and stimulate the CNS to keep regenerating.

Deb

EDIT: And I still say that's not only possible NOW, but highly PROBABLE that that very thing can be accomplished. Not ONE person or MS researcher can cast any "doubt" about that at all! Or tell me that all my research is flawed in any way! The easiest way, even, to get rid of me and my hounding would be to tell me that my research is flawed and here's why. But, they can't. Tell me I'm not onto something, then? And with the support of the NMSS behind me, also? Uh huh. I'd sincerely like to hear one explanation why one researcher isn't jumping at this probable funding, and in an area of research that needs to be focused on. If it's not because my research is "flawed" or not probable to prove efficacious, then what IS it? I don't care how "difficult" a person I may be, I can be "handled". That's easy. That's simply done by keeping the research honest and above reproach. That's not hard to do. You can't tell me that simply because they don't "like" me for any reason, they are depriving thousands of MS patients from this possible avenue of treatment progress? Naw........even I don't have THAT big of an ego!

No matter how you turn it, something doesn't make a whole lot of sense, does it? A person can't help but turn to the "conspiracy" avenues. Nothing else makes sense (especially given, also, that so many lawsuits are going on right now in medicine........involving RICO. That just floors me! But as I have said before, it's not because I don't work in the middle of it - and it still floors me!)

Uh oh........I keep adding here. And after I'm told that my research is "good", etc., I DO ask "why" will they not continue on with it then? That's when I get total silence as a response. The minute I ask "why", especially after being told what I found is valid, they clam up. Honestly. I cannot get one answer to "why" or "why not"? Tell me that isn't odd, at the very least.

Hi Deb.

Doing much better thanks..

I just don't know, until recently I would have said that inflammation was a red herring, that it was a secondary response to the primary mechanism. Controlling inflammation and the immune system would control relapses but that the axonal degeneration and disability would progress regardless. Perhaps slowed, but progressing never the less.

Then I started looking at the Campath trials. Participants who were in the early stages of MS have found their disability decreasing over time after treatment. If the inflammation was not the primary agent then this would not happen (unless of course Campath is affecting another, unknown pathway). So, from being convinced that the immune system was a blind alley I'm now not so sure.

I meet with the UK Campath trial organisers on Tuesday, maybe they'll enlighten me...

Robin

_________________
Do not go gentle into that good night. Rage, rage against the dying of the light.

Robin,

I like you have been following Campath and the claims made by Dr Coles that those who had received an infusion had seen improvements in their disability (implying that some repair work was going on). LabRat who has posted on this site stated that he had seen improvements in his EDSS score and no relapses. Unfortunately, the trial results are not expected until 2006.

I'd really be interested in any information you receive from the trial organiser - early pointers to success (or not), when the treatment would be available if it was successful etc. The claim that it pretty much eradicates relapses would, if true, surely justify it being fast-tracked - the US did it for Tysabri and the reduction in relapse rates is lower (claimed to be 66%).

I did get annoyed when I saw the comments by Professor Smith - 'We have found a potential reason why degeneration occurs, and we have identified an effective therapy to protect the nerve fibres. The therapy appears to work well, and it should be safe and inexpensive, and we are seeking funding to conduct a full clinical trial in MS patients'. I assume because the therapy is inexpensive, that the drugs companies are not interested. But surely this is where national societies / Governments should be stepping in.

It seems to me that we are becoming overburdened with possible treatments - it's taking the phrase 'patient choice' to the extreme. Is it possible that in the not too distant future those diagnosed with ms will have a yearly infusion of Campath, a weekly goats serum injection, a couple of bee stings each month, and a statin tablet and minocycline tablet a day?


Bromley

Bromley,

I'll gather what information I can on the progress of the trials, although I will respect any confidentiality that I am asked to. With respect to the fasttracking there are several issues to consider. Campath has significant possible side effects, as such efficacy has to be clearly demonstrated before approval can be granted (In Campaths case that is for off label use, as it is already approved for CLL leukemia). In addition the European drug approval process is different to the U.S. one. There are currently some misgivings about the U.S. approval process since the implementation of the Prescription Drugs User Fee Act (PDUFA). The following are quotes from Nature magazine.



This is what I believe has happened in the case of Tysabri.



Yup, I agree. But until someone can demonstrate 100% efficacy, as a patient, I'll keep trying everything I possibly can to defeat the monster.

Robin

_________________
Do not go gentle into that good night. Rage, rage against the dying of the light.

That's great that you're feeling better, Robin! Good news!

I am of the opinion that the greater majority of MS does involve inflammation, as you said, and without writing an epic, as I am famous for doing, the bottom line for me, also, is what you both have expressed.

Combination therapy? Fine! Just give me (us) what works! And I'd give my right arm to get all the "politics" out of it all.

(But of course, I'm dreaming.)

Anyway, yes........definitely.........keep us posted, Robin!!

Deb

Question. Why haven't we heard more about the supplement NAC? Is anyone taking currently taking it for their MS? I had never heard of it being used for MS.

I find it quite interesting that a drug company is integrating a supplement with the Copaxone.

If I can just add my .02c worth in, it seems to battle MS we need a two pronged approach. 1 is to stop the attacks, 2 would be to repair the damage. I believe we need to unlock the mystery of #1, for #2 to be effective, otherwise damage may just reoccur. Then again, repairing the damage would be a MAJOR step, even if we had to continually repair it after episodes of demylenation.

Sharon asked


Good question. In a chapter on MS in the book brainrecovery.com, David Perlmutter, a neurologist, does list NAC as a recommended supplement for people with MS.

If I remember correctly, there was no indication in his book that it could only be taken with Copaxone.

--the other Sharon

Exactly-- it is not clear from the study if/why copaxone is relevant to the supposed benefits of NAC. There may be an issue of funding (pure speculation), but it mars this study as there will be absolutely no way to tell if the benefit comes from NAC or Copaxone (unless it's outrageously good, which it really can't be with just one year of data).

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Disclaimer: Any information you find on this site should not be considered medical advice. All decisions should be made with the consent of your doctor, otherwise you are at your own risk.

Because I had never heard of NAC I decided to do some digging. NAC led me straight onto the calpain-calpastatin regulatory system where things got very interesting. I wont produce a mini epic detailing all of the references but the system appears to encompass many of the things we have discussed previously. The Ca(2+) channel, MMPs, myelin protein cleavage, neuronal protection and much more.

Deb, Wesley et al, want to take a look?

Robin

_________________
Do not go gentle into that good night. Rage, rage against the dying of the light.