Saturday, 17 November 2012

Relapses vs. MRI-activty vs. progression vs. brain atrophy

"Some of you who have been following this blog and my recent posts will realise that I have had a change of mind. I have been sceptical about the publications showing a very poor correlation between relapses (frequency and severity) and disease progression. Apart from relapses in the first two years, after the first attack, there is no correlation between subsequent relapses and long-term outcome. Therefore reducing relapses or rendering MSers relapse-free, after the first two years, may not prevent or delay the onset of SPMS and may therefore not impact on long-term prognosis. In fact, we don't have the necessary long-term data that suppressing the relapses in the first two years is effective either. However, the short to intermediate-term data looks very promising; i.e. the earlier, and more actively, you treat MS the better the outcome." 

"Data from several emerging DMTs now supports the natural history studies and the observation that there is a disconnect between relapses and disease progression and importantly an impact on brain atrophy. We have evidence that brain atrophy is a good surrogate of disability progression. Brain atrophy is the biomarker that best captures loss of neurones and axons and is probably the most important MRI biomarker of disability progression to have emerged; in particular atrophy of the grey matter."

"What would you want from your DMT; being relapse-free, without the DMT necessarily having an impact on long-term disability, or brain atrophy? Would you prefer a DMT to delay the rate of brain atrophy, with the promise of this will translate into long-term disease progression? Many of you will say this is a no-brainer; i.e. I want to be relapse-free, disease-progression free, MRI disease activity-free and with a reduction in the rate of brain atrophy to a rate that is expected for age. I agree that it may be a no-brainer, but is it achievable? The current crop of DMTs don't offer this treatment target, or we don't have the data yet, to show that we can achieve this in the long-term."

"May be you should be asking your neurologist what is the evidence that the DMT they are recommending prevents or delays the acquisition of long-term disability and what does the DMT do in relation to brain atrophy? I would be interested in knowing their answers."

"I am at a meeting in Barcelona and I am about to give my "Treatment Highlights ECTRIMS" talk for a second time and will focus on getting this point across! I will update you on the feedback."

110 comments:

  1. If the data is correct then in my understanding everything points to MS being a primarily a neuro degenerative disease like e.g. Parkinson's or Alzheimer's and the inflammation to myelin being secondary (relapses)- would make more sense. So it's back to zero since there are no medications for degeneration right? And are there any ways to measure brain atrophy in patients?

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    1. There may be medications for degeneration but they are unproven. Yes there are many ways of measuring brain atrophy not least many different MRI tests

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  2. If you don't know the answer to the questions is it not a retorical question to ask my neuro something they probably won't know either.

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  3. There will be countless... no, legion sufferers of MS that take DMTs whose hearts have sunk by reading this post. Sam Trucker must be crying into his/ her bowl of cereal upon having contemplated what you’ve just said, Prof G.

    My stance is that whilst DMTs may give a quantifiable measurements of relapse reductions, the neurological damage that is taking place is not directly taken care of. Neurological degeneration and immunology are two separate entities, the correlation not entirely simpatico. The damage in the brain takes years to properly affect the MSers, and by then things are in full swing, like a runaway train careening to disaster.

    Current DMTs are like smoke and mirrors, not effective enough to tackle the long term implications of MS. Too much time has been wasted on the wrong things. We need neuro-protection strategies and remyelination therapeutics. Forget the secondary responses being activated in the body, focus on the things occurring in the brain and spinal cord. Enough with the DMT distractions. They have set us back years and wasted much money. Hell with the DMT mafia. Bring on the remyelination revolution.

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    1. I think there is a problem here. (a) There is no question that the first generation DMT have low efficacy and so we need to see how the new more effective DMT fair, before dismissing the DMT and (b)If you do not deal with the problem of the cause of demyelination then remyelination alone will be fighting a loosing battle. Putting wood on a fire.

      I do not get the Sam Trucker references. Please explain

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  4. Prof G,

    I took the gamble 7 years ago with Alemtuzumab. It's given me 7 years of relapse free life and an MRI ealrier this year showed no inflammation / new lesions compared with MRI two years before. Progression wise - I'm stable.

    I looks like the worst case scenario (in the long run) might being coming good i.e. primaril a neuro-degenerative disease. This isn't good news for MSers, but great news for MS researchers. We're probably looking at another 20 years of research / trials etc etc. I came to this blog for hope (hope for the long-term), but come away with a bad taste in my mouth - all those international conferences, profits for drugs companies, consultancy fees for neuros etc etc, yet no one can tell me what causes the neuro-degeneration or how to treat it. Am I right to feel so let down? Any hope in the future? I can thank Cambridge for all they have done for me so far.

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    1. If you are stable then this is good news. This is the point. The hysteria being created is around drugs that we know have have low level of efficacy. What is important to know is what happens using drugs that actually do inhibit relapsing disease. Sure they are not 100% effective either but I am not going to throw the towel in on them yet.

      "No one can tell me what causes neurodegeneration"
      There are plenty of different ideas on this blog including ideas how to treat it.

      Should we feel let down.
      Well I believe that progress is too slow, and pharma and the regulators and the establishment have had a part in this.

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    2. Yes so lets just ignore the mess we've made of things so far and line up a new batch of drugs to research, Thereby securing our positions for the next 20 years, that should get us nicely to retirement age.
      Oh but first lets get some of these drugs rolled out ASAP before the vascular connection is accepted as the real cause of the damage.
      Lets also give the drugs to new cases as they are the easiest 'target' to treat and baffle/scare with science.
      Your self induced ignorance of the facts sickens me to the core.

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    3. Anon 2:38:00PM

      You should check this YouTube video out; it is about pseudoscience:

      https://www.youtube.com/watch?v=IaO69CF5mbY&feature=youtube_gdata_player

      The vascular theory is not far off the pseudoscience mark; the data simply does not support it. In fact the latest data questions its very existence!

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    4. I don't normally write on these walls, I feel i must say I have felt the change and so i know it exists.
      The 'data' is all there if people would be bothered to look and not just follow the hearsay.
      The problem is no body so far has taken the time to look past the head lines.
      Dr.Franz Schelling's work and his book has all the evidence but so far this is being quite blatantly ignored.
      I try not to take too much from youtube, not very scientific i find.

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  5. Sad if true Prof G. Perhaps the '000s of M+S researchers can make a public apology for leading us astray. MS research has always annoyed me - EAE, mindless comparisons of injectible drugs etc. The brain is a large grapefruit - with all the high-powered microscopes, MRIs, IT tools etc etc, I can't believe we know so little about a disease which affects so many.

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    1. If MS research annoys you, coming here is only going to get your blood boiling. It is about research and that is good and bad news.

      As for EAE mindless comparisons...I agree with you in some instances but it is not fair to blame the models....it is the people who use them and importantly the people who interpret them that are culpable in the hype.

      Apologise...I am sorry but I do not feel an urge to do that public or otherwise.

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  6. I would ask my neuro, but he's a gneralist. he'd say ask the Professors, the specialists, the researchers who have spent all their lives looking at this disease, the guys who've published 150 papers. Unfortunately, they haven't got a clue!

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  7. "The current crop of DMTs don't offer this treatment target, or we don't have the data yet, to show that we can achieve this in the long-term."

    And you wonder why suicide is high among MSers!!!

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    1. The problem is that there is no incentive or compulsion of pharma to try and collect this type of information and this is why is it is difficult to work out the long-term effect.

      The only way is to get every one into a data base and then it would be a click of a button. Who would control the data base? Would you join a database.

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  8. Prof G,

    I'm not sure what you are saying - are you telling us to ditch our current injectibles, not bother signing up for the B cell depleting studies?

    Looks like you should be buying shares in electic wheelchair companies as, mgiven the abvoe, we're all doomed!

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  9. Prof G,

    There are 'U turns' and 'u turns'. You've been talking up treat agressively and early since I started following this blog.

    How does the above link to yuor EBV theory?

    Perhaps when the sangria has worn off, you'll revisit the above - it's left me confused!

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    1. I'm going to stop posting as I read them one by one as I see Prof G has posted below

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    2. If blocking 30% of relapses has no effect on progression why would you think blocking 90% had an effect?

      If what you are doing dosent work.. try something else.

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    3. Because 90% is a long way off placebo effect which is about blocking relapses by 25%

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    4. With respect, that doesn't answer the question, sounds like excuses to keep running down the same blind alley.

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  10. Prof g,

    A few days ago you said "2012 is meant to be the year that alemtuzumab got a license for MS. It is the only drug one the near horizon that offers a potential for a cure. The others are cladribine and bone marrow transplantation".

    However, the above post seems to suggest that DMTs won't make any difference in the long-term????????????

    I think I need some clarity on all of this.

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    1. There is not sufficient data available to state that the markedly effective DMT will not make a difference

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    2. Logic dictates that blocking relapses cannot be a bad thing. The question is whether progression is independent, it may be. But if you do nothing does it come sooner rather than later

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  11. There must be a lot of MSers feeling so scared right now. The great white hope of new DMTs will not be enough to prevent progression, however, if my thinking is correct, DMTs that eventually come on the market may make a difference to future MSers that get them in the nick of time. Unfortunately, we have all missed the boat. Oh well.

    I guess MS is a very serious and dangerous disease after all. I hate the fools that act like it’s merely an inconvenience that can be controlled through drugs. Egg on all our faces!

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    1. "It (MS) will be controlled by drugs" in the light of the discussion as a whole could you explain MD.

      Regards as always.

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  12. Jesus Christ, what a bad start to the weekend. This is the most shocking thing I've read on this blog. It changes everything. Relapses and progression are not linked. They are just a byproduct. This means my MS is progressing right now. It's happening and I can't fix it. These drugs I'm on can't fix it. We've been lied to. I'm never coming on to this blog again. I'm not following anymore.

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    1. People suggest that PPMS do not have relapses so it would seem obvious that progression and relapses are not linked. However is it that PPMS not have any events before diagnosis? I see mice that have one attack and then progress and others that have four attacks before they progress. Both start with the same process and then the disease involves a different process that requires a different solution. This story has not changed. Have I said that all DMT will stop progression I think not, I had not said that any DMT will stop progression no I haven't could some do so yes I think it is possible.


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    2. Better clarify this I am not sure they will stop but slow progression, unless you get at the cause you will not stop anything.

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    3. In mice you are creating a false model. The cause in those cases are never going to be the same as in humans because you are creating the MS like problem not true MS.
      If you don't know the cause how can you accurately recreate it?

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    4. You're right that many of the published animal studies bear little relevance to MS or are shoddy (see MD's post today) BUT before we throw the baby out with the bathwater, there are models which do such as our own model in the Biozzi ABH mouse which do show a great deal of the pathological changes seen in MS, particularly showing a progressive phase mimicking SPMS. This has enabled us to show the validity of symptom control agents such as cannabis for the treatment of spasticity and helped these drugs come to market. In addition the model also allows us to investigate the influence of neuroprotective agents in slowing down progression which is now helping this work to go into clinical trials.
      We are well aware that animal models are by no means perfect but there are some good ones and they are the best we've got at the moment.

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  13. I feel the same as above poster. We've been sold a pup. Whatever we take we're damned. What has Team G acheived since it was formed. I really thought you guys were makign progress and keeping us weel informaed. looks like, no-one has a clue and MS wins again!

    I don't think I'll bother coming to the Research Day. What are we going to learn given that it looks like progression does what it wants and playing around trying to dampen inflammation amkes no real difference - has it really taken 50 years to work this out!

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    1. You have to be careful what you say when you say trying to dampen inflammation makes no difference.

      There is T cell inflammation, B cell inflammation, microglia, astrocyte macrophage inflammation etc They are not all the same thing and you cannot tar them all with the same brush. So blocking T or B cell inflammation may be good for stopping relapses but have no effect on progression or stopping glia inflammation may stop progression but have no effect on relapses.

      We know there is not a simple relationship between relapses and progression and that there is a disconnect otherwise we would not be having this debate.

      If you do not want to come to the research day, that is your option but maybe you should come so that this issue can be addressed to your satisfaction and questions answered. However if you have signed up to come we would be grateful if you would let us know that you are not coming so that your place can be given to someone who does want to come.

      I think the focus of the research day will be aboutapporoaches to deal with progression

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  14. A real Road to Damascus experience for you Prof G. Looks like I've got to accept my fate - disability here we come. If the NHS want to make some savings they should shut down very neurology department - they can't change the inevitable (be it MS, MND or dementia). Won't be donatign any more money to MS research - as above poster says ruined my weekend!

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  15. I'm stunned. This is a set-back of all set-backs. This is the point at which all MSers, progressive and relapsing, are exact versions of each other. This is a leveller. No one is better off other than the people making money out of our misfortune. How apt that it's 2013 next year. Bad luck for us all.

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  16. Prof G,

    I keep re-reading your piece, but can't work out what it's saying. I think it's saying that disease modifying drugs (current and near-future) won't make a jot of difference to the long-term outcome! So why are you recruitinf for trials of such drugs? As many above say, I'm left confused / upset!

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  17. You know, this blog has no right attcking VV or DR Dre because they seem to have been talking sense while the rest of us were complete idiots. This is such bad news Prof G and MouseDoc. I don't think you realise the gravity of what you've just said to us. You need to drop everything and clarify. You owe us an explanation. We have been failed.

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    1. This is not about point scoring. I am as shocked as the rest of you. I always knew that DMTs were toxic junk sold at expensive prices, but the way Prof G has gone from zero-to-thirty has even surpised me. He does owe you guys and explanation and an aplogy for how he has upset you.

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    2. "You know, this blog has no right attcking VV or DR Dre because they seem to have been talking sense while the rest of us were complete idiots".

      "Jajce". Dr Dre and VV are not of the same canvas so I think it is fair to say that neither would want to be tarred with the same brush

      Do you think we go out of our way to attack VV and Dr Dre?...We don't. If they did not come here we would not have cross words. VV has never given the link to his/her Blog site so we can't visit them for a chat!

      They come here and give their world view. Only a sap would lay down and accept their opinion without recourse when you do not agree, just like they like to give a recourse to our opinion. That's debate.

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    3. A debate that your team MD (im happy to say) are loosing hands down.
      Thank god for VV and Dr Dre, that is where our hope lies.
      MS will NEVER be solved by ignoring the facts.
      After 50 years of ignorance it's time to start again with the basics.

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    4. Your team I am happy to say are loosing hands down..

      This is a very sad comment, if you think it is just a them and us thing then you are comming to the wrong place

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  18. I have something in my mind that Fingolimod reduced brain atrophy. Would't that imply that it had some positive effect on the longterm outcome?

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  19. In the end it's quite simple folks: listen to your body. I've been doing it all along when taking one DMT or the other: if you feel much stronger and your fatigue has vanished in the morning then there are good chances that the body or the DMT is working okay. If you take a DMT but you have problems walking it was clear to me that I am most probably progressing so I switched DMTs and can walk longer (some spasticity especially during stress though). I you feel that in comparison to last year you walk for longer periods of time, have less fatigue & memory problems and much better coordination then the answer is: you're doing damn alright no matter what G and the whole world are saying.

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    1. What nonsense. This is the kind of rhetoric that does us no favours. Do you not understand that you’re talking absolute garbage? Prof G has just made it clear that these DMTs do not stop MS degeneration; they are simply a way to dampen immune attacks, not actual brain atrophy. You are in denial and comments such as yours have made me even glummer.

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    2. If you take a medication against pneumonia and it works then there are good chances that your body heals. If you don't take anything and get rid of pneumonia by drinking herbal tea and your body heals then it's okay also. Same goes for MS in a way. I'm not advocating anything just common sense - why should it be nonsense to observe what your body is doing? After all doctors also measure progression by the distances you can walk - I'm doing the same... so chill.

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    3. You can hardly compare a complex DMT to herbal tea. What a silly comparator. These drugs we're on are very dangerous. We take them in good will because our MS team tells us they're ostensibly doing more than what is true. You are patronising me by making such statements.

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  20. I think you have misinterpreted the post. Of course relapses count; please see my previous post:

    http://multiple-sclerosis-research.blogspot.co.uk/2012/09/do-relapses-count.html

    What I am trying to say that the link between relapses and disease progression/brain atrophy is not clear or necessarily there. In other words, the fact that a DMT may reduce relapses by a certain amount is not a guarantee that the DMT is going to prevent brain atrophy or long-term disease progression (over decades). The corollary is that a drug that works on preventing brain atrophy and hence disease progression may not necessarily suppress relapses. In other words the two processes, that on the one hand cause relapses and the other hand cause progression/brain atrophy, may be different. Those that cause relapses and MRI activity (new lesions) are inflammatory and those that cause brain atrophy and disease progression are neurodegenerative. What we need are drugs that reduce both relapses and disease progression/brain atrophy or combinations of drugs that do this. In fact this is what we are trying to do with our oxcarbazepine-CSF (lumbar puncture) trial; add a neuroprotective treatment to IFN-beta and glatiramer acetate.

    What I am saying about relapses has been debated endlessly on this blog. Prof. Ebers has been saying this for years. What we need to do is target all outcomes, relapses, MRI activity (new lesions), disease progression and brain atrophy. I will post a YouTube lecture on this to explain the concepts more clearly in the next week or so.

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    1. Professor G, you're still saying current DMTs do not stop us from slipping into progression. These processes that cause neurodegeneration are still untreatable. Your post still needs to be properly discussed.

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    2. Actually doctors like him have been saying it for longer & the same goes for pharma - you & I just need to read the small print - in the studies it always been something like 50% less relapses but only 7 % disability progression (for Avonex I think). So I (a thinking person I reckon always wondered why the discrepancy). It's self-explanatory. I was shocked at first then my GP reinforced me in my suspicion. That's why I changed meds to fumarate on my own risk really (and not e.g. Aubagio) because I only cared for disability progression in the first instance (although relapses free is a bonus). Fumarate has 30% reduction of disability progression - the highest what current DMTs can do for you - I figured it out months ago so what's G is implying is not really news. I reckon by simple logic that DMTs which would cut disability even further are in some way neuro-protective and thus delaying secondary progression, though.

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  21. Prof G,

    How long before we see treatmetns which addres neuro-degeneration?

    Depressing post. Depresing disease.

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  22. Sad that it's taken 60 years to work out it's a neuro-degenerative disease at heart!

    MS researchers are like King Cnut - but the MS tide kept coming in nevermind what they did / prescribed!

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    1. It has been clear that there is a major neurodegenerative component to MS for many years this was clearly evident when CAMPATH-1H was not stopping progression. That was published in 1999, likewise the MS pathologists reawakened people to neurodegeneration being a problem in 1997 in UK and 1998 in USA. They also showed that inflammation (macrophage/glial inflammation not T cell inflammation)is associated with nerve loss.

      In terms of prescription-Neuros can only prescribe what drugs they have the powers to prescribe. Even if they want to prescribe something else they can't because of the rules. In that respect you need to blame pharma and the establishment.

      OK Test the hypothesis that early aggressive treatment has no effect and treat people in CIS with the most powerful DMT and then see what happens. But in UK they are not first line. Give them all generic cladribine as they are asking too much for Lemtrada. We have the answers if humans behave like animals with autoimmunity. Start early and aggressively because even at first attack there are nerves destined to be lost down the line and have too many attacks and then there is a progressive process set in motion that slowly creeps forwards. Therefore, DMTs needs to do something else.






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  23. The comments almost made me wonder if I've been reading the same blog.

    I never got the message that DMTs prevent longterm disability progression. Even the recommendations for early aggressive treatment come with the obvious condition that we don't yet know for certain if the strategy will work.

    It will be the same when neuroprotective & remyelinating treatments become available. We will not be sure of their long-term benefit before 10-20 years of use

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  24. This blog has been going just over 3 years and we are are yet to hear about any real breakthoughs e.g. cause, processes behind neuro-degeneration.

    The only hope I take is that there are quite a few neuroprptective trials underway or just about to start. These need to be driven forward quckly - no need for the usual snail's pace of MS research. Most of the agents are for conditions such as epilepsy so ahev a proven safety record. if the look like they are having an effect we should have the choice to take them. I really hope one of these agents can be brought to market within 3 years - I'd really like to preserve what CNS I have left. I long for the day when doctoring takes over from researching in terms of MS. Just want to get treaments which slow own disabilty, not keep seeign endless research papers and theories. More than happy to get a couple of doses o Alemtuzmab, start me on one of the neuro-protective agents (amelioride), and a course of anti-EBV tablets. Would rather taek a risk on these than have to do he on way trip to Dignias in 15 years time!

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    1. "One can be brought to market in 3 years".

      We are doing a bad job (I know this will draw flak) but we have been showing you (the readers) that it is a slow laborious process and it not possible to do the studies and drive through the legislative process even if you had all the cash in the world and nothing mess-up along the process.

      The only way this can happen is if there is a change in the legislation to change the drug development and re-purposing strategy and also the change in the process of Evidence-based medicine

      Maybe after positive phase II allow prescription of the drug whilst the phase III trials are ongoing but what happens after it is shown to be a bust.

      No drugs are inert and all of them have side effects..I am not a clinician and I would feel that I would like to be gung-ho and prescribe what I think will work, but the problem is that we have created a litigious society that blames the doc when it all goes t*ts- up and a Government that is controlling the purse strings. It is hard to have it both ways

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  25. Am I right in thinking that the MS-Stat trial reported a reduction in brain atrophy?

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  26. Woah! Everyone needs to calm down a bit, I think! Talk about making 2 + 2 = 7.

    Firstly, there has not been some groundbreaking discovery. Prof G is simply thinking out loud. No-one knows the answers to the things he is discussing and there are plenty of neuros on both sides of the thinking.

    Secondly, a lack of a link between relapses numbers and transition to SPMS does not mean that DMTs don't help delay or prevent this. The pathogenisis of MS is so complex and the mechanism of these drugs so poorly understood that it is perfectly likely that some of them may delay progression as well as reduce relapses. Many of the newer DMTs have shown positive effects on atrophy for example.

    Thirdly, the mean time to SPMS is 20 years. Relapses are what makes MSers unwell before then. Is reducing them a good thing? Yes. The guy whose had 7 good years after Alemtuzumab should be happy for those well years. Would I take a DMT just to be more well for the next 20 years - absolutely.


    Finally, even if progression does occur, it does not mean definite disability. The stats simply don't show that. Dignatas levels of disability are extremely rare so everyone just needs to get a bit of perspective to this discussion...

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    1. You spelt whoa wrong.

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    2. Yep take a deep breath every one. I am sure Prog G will need to respond.

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  27. Mad as Hell, and going to take it Anymore!Saturday, November 17, 2012 8:20:00 pm

    Forget what this blog says about DMTs. We need stem cells.

    Susan Solomon’s lecture at TEDGlobal 2012 in Edinburgh, Scotland about her work at The New York Stem Cell Foundation proves how wrong the current wzy of doing things is, and how new therapies to effectively treat progressive multiple sclerosis are within grasp: http://youtu.be/CY_Oj59WlL0

    Don’t lose hope. Good times are coming. promise.

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    1. Great I hope we all agree to be Genome sequenced at birth so we can select which designer drug we will respond to but this will be expensive and who will control the information? In the UK they have been making the state throw away of genome data base. So in the video the stem cells are not used as repair factories but as a tool for drug development, but is she living in cloud cuckoo land to think that we will be re-purposing old drugs.

      If people can not make cash out of the situation then it does not happen and I would be surprised that any discovery from the work described would not be patented to the hilt to make a few bucks.

      However I do believe that we should be using human cells rather than animal cells to do research for many years we have been jumping through hoops to deal with the ethics of using living animals when people doing test-tube work have been using animal cells to do work, without having the same ethical issues and licenses to go through. In this day and age there should be be noo ethical reason to use animal cells as all human cells can be grown from stem cells...or can they. This costs loads so mean less work and less progress.

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  28. So we are back to lifestyle changes including diet, exercise, stress reduction and vit-d.

    http://www.overcomingmultiplesclerosis.org/

    More or less the same approach as what it takes to prevent other neurodegenerative diseases.

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  29. I disagree that lifestyle changes are the only answer, but lifestyle changes of course can have benefits

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  30. Back in the 1950s, when I was born, multiple sclerosis was commonly felt to have an infective cause, but nobody could decide what the infection was, so gradually autoimmunity won the day.
    When I was in my twenties I ran away from a diagnosis of MS because at the time there were no DMTs available, just steroids as and when needed. At the time my relapses were few and far between giving seemingly total recovery. More than fifteen years later I was still able to go on walking or cycling holidays putting most people to shame in the distance I could easily cover.
    Things began to change just when DMTs became available in this country: although I still had relapses it became obvious that my disease had become progressive, so there was again nothing available for me. I was given an official diagnosis of SPMS in 2003, at the age of 43. I had lost e use of my right hand and could not walk any distance unaided.
    Twelve years later having my MS treated as an infection, though not by my neurologist, I appear to have completely pushed back the disease. I have had no relapse in this time, no new lesions, even some newer lesions vanishing. I have regained totally the use of my right arm so am able to work again as a professional artist. My walking is improving.
    So maybe now is the time to look again to the old view that MS is cause by an infection.

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    1. http://multiple-sclerosis-research.blogspot.co.uk/p/charcot-project.html

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    2. Yes we aim to test an idea that MS is a problem of a virus which is the heart of the problem that is what the charcot project is all about

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  31. It's interesting what you're saying Sarah. What drugs were you on after 2003 then? I also believe it's caused by an infection (sometimes the oldest theories are the best) since I have elevated antibodies against pretty much every infectious disease out there (measles, pox, EBV etc.) & my MS probably started around the time of a grave pox infection in 2003 (although un-diagnosed till 2010).

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    1. Er, thanks but I have been tested for chlamydiae and it was negative. I hoped you were treated by a GP not a new Age doc (have tried that route and it's nothing for me). I think I will wait for the Charcot Project. Sorry to say but your post sounds like a plug for this doctor, be it your hubby or not.

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    2. Hardly a plug: he makes nothing out of it and besides, antibiotics are not “new-age stuff.” I don’t go in for that sort of thing!

      If you look properly at the very well referenced pages the evidence is hard to refute.

      C pn is notoriously hard to check for: in fact I was only 1:64. My GP did treat me though, under recommendation from my husband. Some other GPs will do likewise, but some won’t.

      Delete
    3. Dear Sarah
      We have posted about this in the past and believe that David Wheldon needs to do the studies to give us the evidence base.

      Delete
    4. Sarah LonglandsSunday, November 18, 2012 4:25:00 PM

      Using the research done at Vanderbilt University by Stratton and Mitchell, my husband, Dr David Wheldon, treated me for chlamydophila pneumonia using doxycycline, roxithromycn and pulses of metronidazole, together with a plentiful supply of probiotics. This was finished in 2008.

      You can see more by reading David’s MS treatment pages:
      LINK REMOVED.
      MOUSE DOCTOR SAYS IF YOU ARE INTERESTED DO YOUR HOMEWORK TO FIND PAGES.

      By the way, I should have said nine years when I wrote twelve: it was twelve years sice I first realised that my disease had taken a progressive turn but I was still reluctant to seek a diagnosis.

      Delete
  32. Re Sarah Longland's remarkable story: what is the evidence for using these medicine in MS?

    ReplyDelete
    Replies
    1. http://multiple-sclerosis-research.blogspot.co.uk/p/charcot-project.html

      Delete
    2. This is not the evidence, the charcot project is about viruses and not bacteria protozoa fungi or other things

      Delete
  33. Mouse-Doctor asks me to give the evidence base. I’ll try and be brief.

    Charles Stratton and I reviewed the evidence some time ago. (Stratton CW, Wheldon DB. Multiple sclerosis: an infectious syndrome involving Chlamydophila pneumoniae. Trends Microbiol. 2006 Nov;14(11):474-9.) The evidence is strong if not conclusive. The organism, a respiratory pathogen, was first detected in the CSF of persons with MS in 1999 (Stratton and Sriram). These results have been repeated elsewhere. A conjoint study of C. pneumoniae gene-sequences in CSF in patients with MS and other neurological dieases gave broadly similar results when examined by two separate laboratories using different methods. A prospective study revealed a new respiratory infection with this organism just prior to an MS relapse (senior author Hintzen). A statistically significant elevation of antibodies to Chl pneumoniae was seen as relapsing-remitting disease became progressive (Munger and Ascherio). In a limited pilot study, antimicrobial therapy directed against Chl pneumoniae reduced the rate of loss of brain mass (Stratton and Sriram). Minocycline (which is also active against Chl pneumoniae) markedly reduced Gd enhancing lesions (LM Metz and others): to be fair, these authors attributed this effect to immunomodulation. Part of the problem is that this organism is difficult to grow; the methodology has to be fastidious. Some laboratories can grow it; some can’t. Quality control, so effective in general microbiology, is difficult. So. Compelling if not conclusive. Compelling enough for me try (fairly) harmless antibiotics with Sarah and a number of others. I’ve tried to collate the evidence on my website to help others. (link above.)

    Why these ideas attract so much hostility I don’t know. I suppose it is because they involve a huge paradigm shift. I believe it’s called confirmation bias: people tend to accept evidence that favours their existing point of view and angrily reject that which undermines it. Sarah’s neurologist was enraged at my treating her and refused to look at the improvement on follow-up MRIs. Truly, we are wedded to our axiomatic framework at the expense of our humanity.

    I’m just about retired from medicine so I am probably more old-age than new-age in my approach. The best, David Wheldon.

    ReplyDelete
    Replies
    1. "These results have been repeated elsewhere".

      I suspect that Prof G could have something to say here, but he could not replicate the works of Sriram and a large number of Labs in UK, Iran, Italy Sweden, USA such as the CDC (If the centre for Disease control can not find a bacteria is it there?) did not replicate the finding of Chlamydia. Bagos et al in 2006 Mult scler. 2006;12:397 reported following analysis of 26 studies that even though the presence of Chlamydia is clearly more likely in MS patients, these findings are insufficient to establish an aetiologic relation. However this aspect is not my passion.

      However I can accept that in some MSers there is evidence of Chlamydia, just as this can be found in other neurological diseases and will accept that relapses often follow upper respiratory tract infection

      However, even if I accept that Chlamydia is an aetiological factor the important point is where is the evidence base? I think it is great that you wife has done well but I need to see an 'n' and the n should not be just the n in anecdote. How many times has the treatment been replicated and found to be effective and ineffective as you have been posting this for over 10 years.

      Based on your website there is a lengthy period of anti-biotics and a poly pill of vitamins and nutriceuticals. Whilst you and I can make a coherent argument for these, again where is the evidence? A trial with roxithroycin was apparently negative

      Paulo Zamboni has likewise claimed a treatment for his wife based on unblocking her veins. This and anti-biotics do seem to be mutually exclusive. There are thousands of people who believe in CCSVI and thousands spent thousands having treatments, but because there is no sciencific rigor to this we are no the wiser about the real value. Likewise there are beestings etc.etc. I know of an Mser who swears by their cocktail of nutriceuticals and is doing well. Is it chance or is there something in this?...we do not know because there is no evidence base.

      The internet is full of potential treatments and we want people to get treatments from Doctors and Neurologists and not the postman. Armchair science is the easy way but surely if you believe in something there must be a will and a way for you to get that evidence and that will stop hostility.

      Team G are actively involved in a fairly harmless anti-viral link, but we are going to do the studies and then we can put the sword to the idea or get the information published, this is what I think would be the best way to move forward.

      Delete
    2. Could you explain the bit about 'he could not replicate the works of Sriram'?

      Delete
    3. The suggestion that all MSers or significant proportion had Chlamydia.

      Delete
    4. 'The internet is full of potential treatments and we want people to get treatments from Doctors and Neurologists and not the postman.'

      Ah. The Ad hominem attack.This is possibly the poorest form of logical argument.

      Delete
    5. Oh the chewbacca defense

      An ad hominem (Latin for "to the man"), short for argumentum ad hominem, is an argument made personally against an opponent, instead of against the opponent's argument.

      It is nothing personal if you check out the blog this is a consistent stance. We want empiral science not anecdote...that is the logical approach. You are a Docotor and should understand this. When I asked for an "n" there was no response.

      Yes I know this was not a Chewbacca defense

      Delete
    6. http://en.wikipedia.org/wiki/Chewbacca_defense . If it doesn't fit yu have to acquit.

      So maybe the Alternative Jerry Maguire attack "Show me the empirical supportive data"

      or maybe the Popper Attack.... Disprove your hypothesis.
      Oh a potential problem here based on reading the literature. Hypothesis can be busted. It is selective reading I hear you cry..so you have to do a lot more than put pen to paper to convince people otherwise...Oh back to the Ad hominem attack.

      I accept you believe that you idea is the beesknees, it may well be, but we need to see the supportive evidence done to standards currently acceptable as providing reliable evidence other wise we get fab things like the Goat serum saga, which was peddled by some well-intentions doctors.

      Delete
    7. Well, actually, I have provided the evidence. You have produced just chaff in reply.

      For instance: "A trial with roxithroycin (sic) was apparently negative" You might care to read Dr Stratton's and my reply in the journal Infection in 2007. Here's the link: http://www.ncbi.nlm.nih.gov/pubmed/17882356
      I hope the link works.

      the best.

      Delete
    8. I have been doing my day job

      To quote from the link you provided

      "Progression in both primary progressive (PPMS)
      and secondary progressive MS (SPMS) and relapses in
      relapsing-remitting MS have been effectively halted".....

      Sounds great

      "These and other case reports will be submitted for publication after an extended follow-up period. Initial results, though encouraging, will need to be validated by comprehensive multicenter trials ofcombined antibiotic treatment aimed at all phases of the organism’s life-cycle". C.W. Stratton, D.B. Wheldon 2007

      It is now 2012 so where is the peer-reviewed publication, I could not find it in pubmed? And where are the trials required to validate the approach?

      Any chance of Class I evidence appearing?




      Delete
    9. I hope so.
      But it will take time. Out of patent antibiotics don't attract your pharma funding. So it will take time.

      Delete
    10. My Pharma funding comes off alot of hard work, but accepted Generics are hard studies to get funded but again with hard work they can be done, e.g simvastatin

      You have a a patient population with an unmet need, your treatment you claim to work in PPMS, SPMS and so you have no pharma competition and you have a group of people who I suspect would be happy to be volunteers.

      You claim you have data, so now you can find a statisitican to do the power analysis to say how big d your trial needs to be with a blinded placebo and active arm give them both nutriceuticals the main issue is the anti-biotics. Problem is many MSers get infections that need to be dealt with.

      You have set up your hypothesis but the problem is alot of people doubt the chlamydia story because they cannot find evidence of chlamydia (You can debate this but this is a majority view on wieght of publications). Maybe dress it up with the need for anti-biotics as many people may accept that MS activity often follows infection, hey you may get prof g support on that.

      You do placebo arm and active arm...double blinded. You go to the generics companies and ask for free drug and help to support study.
      You will need pharmacy for making placebos

      You should be able to find an academic consultant nearbywho can help in you with getting the ethics and writing protocol, if you can not do this. It may help you get funding go to on of five academic centres.

      You apply for charity funding, if you dont have imaging it will reduce cost but may de-evalue your study. You have to make it happen. You can get innovative studies from most socieities

      You have used the internet to lobby your cause, fine, now create the proof that will compel docotrs to take up your approach. It needs to be your hard work, otherwise it is fad idea and fads invariably are put to the sword at some time

      You say my reply is chaff, but I hear nothing in reply but excuses about how hard it is. It is not hard to write a paper e.g. Ram writes one every month or less and there are plenty of journals, even for anecdotes. So no publication is an excuse after 5 years. If you believe something you find a way to make it happen otherwise it is arm chair science

      Delete
  34. Lots of all these posts are way over my head (and I cannot be bothered with the bickering) - but I recently watched the nmo patient information day (Guthy Jackson foundation) and they seem to thinking along the lines of bacterial infection being a cog in the start of nmo. My first MS/NMO symptom developed in tandem with nephew and his chicken pox I suspect this was a cog to my disease but its obvoiusly so much more than one thing to trigger these diseases and they way they progress.

    ReplyDelete
    Replies
    1. We also think there is infection in the cog of MS

      Delete
  35. Oh, well, Mouse Doctor

    I’ve put the evidence forward as best I can. You seem a little anxious, but it’ll all come out in the wash.

    ReplyDelete
    Replies
    1. Not sure it will come out in wash, becuase if people do not look, how can it come out? That is why people making the idea really have to drive it forward, because others will not necessarily do it and Ideas get left and forgotten. That is sad if it is something that potentially works

      Delete
  36. I do believe this might be the best read I have ever seen on this page, Hurrah, now maybe the blinkers are coming off we might be getting on to the first step of the ladder. outside the box even wow, how many years did that take ?

    ReplyDelete
  37. e.g. Cpn, Lyme, Methanol, might be a place to start, so many offenders need to be considered.

    Remedies, before immune suppressing drugs.
    i.e. Food, Digestion, curcumin, magnesium, Vit D, Bs, .....

    ReplyDelete
    Replies
    1. Don't mention the methanol it will set rmforall off again and especially has he did a sensible post yesterday.

      Yes there are so many offenders, but how are we going to assess them properly, Holland and Barratt and others are very happy that there is confusion as one can end up buying and trying stuff with no evidence base and no real activity. I am sure we would all like the answers

      Isn't curcumin supposed to work by immune suppressing?

      Delete
    2. http://www.ncbi.nlm.nih.gov/pubmed/12570874

      "Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element."

      It's along the lines of BG-12 as an antioxidant and nrf2 activator. If the brain is subject to excess oxidative stress, curcumin is alleged to help.

      Delete
    3. OK I stand corrected.
      Now the question is how much curcumin do you need to achieve the effect in the papers a spoonful or a lorry load?

      Delete
    4. well one things for sure, we wont get them assessed by having our 'experts' chasing their tails on old theories or spending Tuesday mornings writing responses on internet bloggs?
      Ridiculous.

      Delete
  38. I am glad you wrote this. It is about time. The beta interferon /copaxone "risk sharing scheme" revealed in a large epidemiological study that these drugs were not making a difference in progression even though they were making a difference in relapses years ago. The neurologists roundly questioned the study as if it were a given that these drugs have to be making a difference--when in fact the study was right. They don't.

    The DMDs are a distraction and their very existence and the marketing machine that pushes them is closing minds to ANYTHING else. Just go to any neurologist and ask about CCSVI or chlamydia pneumoniae and you'll get an earful about "Oh no, that is nothing. We know that it can't have anything to do with MS because the therapies we have work." THe therapies we have don't work as some of us already learned, yet we are treated like some outlier when the truth is we are the norm!

    This is a physicians placebo--they didn't used to see healthy MS patients because they didn't have any drugs to give them and their disease was unmistakable--ergo, patients didn't come in unless they were so disabled they were desperate for a spasm med or something. The presence of healthy MS patients in the office (ie those with early MS that can be diagnosed with MRI and placed on drugs that gets them in every few months)has resulted in widespread belief in docs that the DMDs were making a huge difference because the meme about people doing so well today is repeated at every conference among neurologists and their on office is full of these functional patients. It was the anecdotal evidence before their eyes that they put faith in--the office is full of healthy people so the drugs work. How scientific is that?

    It is about time we realize that the DMD marketing budget has influenced medical doctors in inappropriate ways. The widespread belief that DMD stops progression --regardless of package insert- was carefully nurtured by public relations campaigns. Teva and Serono both got an FDA warning letter for misleading advertising about progression and their drugs. It was the doctors they were misleading.

    This should hopefully result in some compassion for MS patients. COmpassion and more innnovative treatment instead of an offer of more DMD. Autologous stem cells in high doses to suppress immune activity AND repair degenerating brain tissue for example ought to be front and center right now. Let people who are SPMS get this NOW on compassionate basis and follow them. John Gurdon Nobel laureate for stem cells said people should be allowed their own stem cells if they want them because they'd probably be willing to take the risk.

    but I am betting that there will be a new blog in a week or two--it'll be all about BG12 and how great that is going to be to address the "degenerative part" of MS.

    I say bunkum. All this advertising about how great this stuff is is nothing more than a soap commercial for whiter whites coming all wrapped up in a "scientific evidence" package that is swallowed hook line and sinker by the people who control our availability to treatment.

    ReplyDelete
    Replies
    1. Absolutely spot on, and if I was a cynical person I would suggest that all of this hullabaloo is merely orchestrated to get alumtuzemab to market as quickly as possible, on the "you need early aggressive treatment, delivered to pwms within 2 years of dx" and then lets see after 20/30 years if it has any effect on progression.

      Delete
    2. I think you need to take your IFN-beta/GA or 1st-line injectable blinkers off. The goal post have moved. We now treat-to-target, i.e. switch non-responders to other drugs. The DoH scheme is out of date, we don't manage MS the same way anymore. You also need to look at DMTs in terms of the newer more effective agents. The data on these agents is much better!

      Delete
    3. So does this study out today offer hope to halt progression ? or is it another barking up the wrong tree ?

      http://www.newscientist.com/article/dn22513-blood-cell-disguise-halts-multiple-sclerosis.html

      Sorry can't find the full paper.
      Regards as always

      Delete
    4. This is what researchers were claiming about IFNb back in 1997:

      http://www.ncbi.nlm.nih.gov/pubmed/9270562
      Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG).

      "Results in this report demonstrate that IFN beta-1a treatment is associated with robust, clinically important beneficial effects on disability progression in relapsing MS patients."

      You claim the same things about newer drugs. Why should we believe you?

      Delete
    5. Re: " Why should we believe you?"

      Please don't! You are free to believe what you like. That is the beauty or curse of a democracy.

      Delete
    6. And how is believing what we like helping us?
      Some turn to these people for help as they claim to be at the cutting edge now we find out they steer us in the wrong direction.
      I believe 100% my MS is caused by blood flow through out my whole body, but these guys are still protecting their projects and not even looking at that side of things. i cannot get treatment for my blood flow because they don't like the idea and as one of MS society researchers was more than happy to tell me 'they have all the power in this debate, you have none'.

      Delete
    7. Andy Clarke
      The paper you describe is basically a repeat of some work we published a few years back but our paper was not cited Grrrrrrrrrrrrrrr!
      MD posted on this "Antigen coated beads the New (Old) Cure.
      It's stopping inflammatory disease and not influencing progression per se.

      Delete

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