What does a black swan have to do with MS?

Have we got the autoimmune paradigm of MS wrong? #MSBlog #MSResearch

“I was involved in a heated discussion yesterday at a meeting in Germany that centred on the current, and future, DMT market for MS. The opinion was that it would expand and continue to support several new drugs and classes of drugs, for example safer and more effective immune modulators and neuroprotective, remyelination & neurorestorative therapies. What do you think?”

“This current perspective is based on the premise that we have got the cause of MS and its pathogenesis right. What if we are wrong and MS is due to a viral infection? I have made the argument for a paradigm shift on this issue on many occasions.”

“This figure which attempts to illustrate the current dogma, in relation to the pathogenesis of MS, may be incorrect. In other words the inflammatory, or so called autoimmune reaction, is secondary, possibly in response to another trigger. An obvious hypothesis is that MS is due a virus. This would imply that therapeutic strategies targeting primarily inflammation (shaded box), which reduce or abolish relapses and focal MRI activity, may have little impact on the underlying neurodegenerative processes that drive progressive MS (lower half of figure). If this was the case relapsing MS would simply be converted to non-relapsing progressive MS. This experiment is underway; MSers with active disease rendered relapse-free with more active DMTs are being followed to see if they present in 10, 15, or possibly 20, years’ time with secondary progressive MS. Should we wait for this experiment to read-out before pursuing other hypotheses? Of course not, people with MS cannot wait this long for an answer. This is why we promote active early treatment under the autoimmune umbrella and have simultaneously launched the Charcot Project and are doing an exploratory a trial of raltegravir, an HIV drug, in MS. We also are continuing to try and drum up support for doing a trial of an anti-EBV drug in MS.”

“Interestingly, drugs that target B cells, in particular B cell depleting drugs such as anti-CD20 (rituximab, ocrelizumab, ofatumumab) monoclonal antibodies also target EBV and are very effective in MS. Anti-CD19 which also targets B cells will do the same as anti-CD20; hopefully anti-CD19 will be even more effective than anti-CD20 as it targets plasmablasts as well.”

“If the viral hypothesis turns out to be correct this could potentially destroy the current DMT market and replace it with something new. Events, or paradigm shifts, of this nature happen more frequently than expected. A good book to read about these improbable events is ‘The Black Swan: The Impact of the Highly Improbable’ by Nassim Taleb. The book focuses on the extreme impact of certain kinds of rare and unpredictable events (outliers) and humans’ tendency to find simplistic explanations for these events retrospectively. This theory has become known as the black swan theory.”

“Is a black swan event about to happen in the field of MS? Watch this space.”

Other posts of interest:

Multiple Sclerosis Research: Targeting B cells
12 Aug 2013
Another target is CD19, which to me is even more appealing than CD20 as it is expressed on a larger number of cells including plasmablasts. At present we are recruiting RRMSers for a trial of MEDI-551, which is an antibody …

38 thoughts on “What does a black swan have to do with MS?”

  1. Is there any even anecdotal evidence that those treated with alemtuzumab quite some time ago haven't gone on to develop secondary progression? Presumably anyone treated early in the availability of the drug would have had severe disease and therefore would have been expected to go on to secondary progression. Even anecdotal evidence of a lack of development in this (I assume small) group would provide some hope that the disease has to some extent been halted. I'm not aware of any information about these patients that would help inform the decision when considering aggressive therapy.

    1. Maybe they have done so well…they don't read about MS anymore or enter the Blogosphere.Maybe Cambridge has some clues?

    2. Look on this blog for 14 Feb 2012 and the guest post from Alisdair Coles. He said some info in a couple of months, but nothing published yet that I know of

    3. I remember that dr dre once challenged prof g to confirm how many of his patients treated with alemtuzumab went on to develop SPMS because Dre reckoned alemtuzumab isn't all that great. Prof G didn't respond. I can understand why. Dr Dre is a scaremonger.

    4. Not to conjure up trolls, but I think it's fascinating to compare the online behavior of those treated with alemtuzumab (they don't talk to much about it) and those treated with less conventional therapies (they evangelize about it constantly).

    5. Casting my mind back, we have had a few posters who have been treated with alemtuzumab (at least one from some years ago) and all were very positive. As you suggest, perhaps they quieter they are the more effective the treatment?

    6. Are you suggesting Anon 1:25 that there is a quiet competition between MSers who are on effective drugs and those who are on the conventional ones? What for? Are humanity really that nasty? Hope not.

    7. I don't think that's the suggestion at all. I think those who have been successfully treated with alemtuzumab just want to forget about their MS as much as they can- they're not relapsing and not having to have regular injections/infusions to remind them. I think they're just counting their lucky stars that they were able to get the drug

    8. One would have hoped that if things had been done properly we would of had a real answer by now if the tens of thousands were getting something that offers robust benefit.

    9. I see your point, Maren. I (Anon 1:02) wasn't just thinking of those treated for jugular abnormalities, however. There are several other popular alternative therapies that have prolific online fans (LDN, various diets, etc.). I'm not making a judgment call. I'm just wondering what drives the difference in web presence. I mean, not even one alem activist, out of 1000?

    10. Alem used to be available outside of trials. There was a lot of off label use, but I don'rt know the numbers. The evidence on alem is in- it prevents relapses in the majority of cases if given early enough and may allow the body to recover some lost functions. Whether it prevents or slows down progression is unknown as yet. It has potentially serious side effects- not everyone gets them, but then CCSVI has potentially serious side effects, and even LDN has some side effects. The problem with the other treatments is whether they have any effect on MS at all. I wouldn't try to persuade anyone to use alem (when they can get it), just give them the facts and let them make up their own mind in consulation with their neuro. I think alem is great

    11. In my experience of ~40 RRMSers treated with alemtuzumab it delays the onset of SPMS. This however anecdotal and needs to be tested in controlled trials. Cambridge has the data and will publish it in due course.

    12. "[A] lot of the alternative therapies have little to no side effects, which would make it easier to advocate them with a clear conscience."Maren, Please read this site and disabuse yourself of this erronous assumption.: http://whatstheharm.net/alternativemedicine.html"I'm not making a judgment call. I'm just wondering what drives the difference in web presence. I mean, not even one alem activist, out of 1000?"Anon 9/7/13 3:17:00 am: A reason may be that treatments that are based on science and are evidenced-based don't need to rely only on Facebook or YouTube activism to drum up support. Keep in mind that anti-vaxxers and HIV denialists rely soley on social media to spread their message.

    13. Anon 1:02/3:17 here again:But why do you think those on alternative treatments feel they need to spread any message at all? Why do they need support for their therapies? I'd love to look at this from a Social Identity Theory perspective. I'm guessing activists are not drumming up support. Rather, they're reinforcing their own group identity, which is really an "outgroup" that is trying to increase its social distinctiveness. (I got that from Wikipedia under Social Identity Theory, so it's probably trustworthy /j.)I'm interested from that perspective whether a blog like this threatens that social identity, because it's questioning their beliefs. Or whether it's reinforcing their identity because they're on the front porch with the big dogs (or mice, as the case may be.)Hahaha. I'm so glad there's an Anonymous button here.

    14. Prof G,Bit depressed that Alemtuzumab only delays the onset of SPMS. I took my chances with it and it's kept me in remission to date (8 years). I was hopeful that for some of us it would prevent SPMS. Looks like I'll be relying on the Cambridge team to come up with something else to ward off SPMS.

    15. Don't get depressed. We simply don't have the answer to whether or not it prevents or delays SPMS. I don't want to peddle false hope. We simply need to wait 15 to 20 years to get an answer. What we do know is that there is a time window in which it works. If you have already acquired a lot of disability and are progressing it does not appear to stop progression, but may slow it down. This is why early and active makes sense.

    16. "I'd love to look at this from a Social Identity Theory perspective".Then why don't you Any comments from the AM evangelists? :-)…Maybe not Dr. Dre may start ranting

    17. MD: I was being rhetorical (or just writing sloppy). I obviously am looking at this from a SIT perspective. :PMaren, What benefit do you think people who actively dislike this blog get from coming here?

    18. Good questionVV?Dr. Dre?Troll from? Serious responses rather than the usual crud.Maybe they love it (The Blog) really….as it is a place to let off steam…..However the best place for that is a Kettle:-).Best information source…..we will see.Prof G has been nominatedAlso to put my oar in "Alem is not available outside of trials" but it was available in the context of B cell leukaemia treatment for quite along time, before Sanofi/Genzymne withdrew it prior to a repackaging and relaunching as Lemtrada. I suspect many people with MS got it off label.However to address your question again "What benefit do you think people who actively dislike this blog get from coming here?"….I would suggest also to find out what ProfG has said about their products…its not just MSers who visit….but Marketeer hoping to control the information flow

  2. MD, losing touch with these people (for all the right reasons) would be a loss in terms of broadening knowledge regarding the impact of the treatment they'd received. It shows how important it is to keep records of treatment and outcomes – maybe the MS Register can/will help, albeit anecdotally rather than strict scientific information?

    1. I am surr that cambridge will be following people in their care to monitor this. I agree we appear to have caught Dr A spinning a porky.However you have to remember that getting papers published can take years. Also the company would like to control flow of informatio about their drug.Add the years on from when the five year data was published to give you an idea of when to expect the ten year data

    2. Thanks for your reply. Not surprising that touch is lost, however also likely that Cambridge will keep track (I hadn't known the connection when posting before).Sun is out in London – enjoy the weekend…quick!

    3. I received my Alemtuzumab at Cambridge. Fantastic care from Dr Coles. I would hate him to waste time on a blog. A blog is just words. Coles and co have got a real treatment to patients. Words in blogs haven't. Alemtuzumab has helped me fantastically.

    4. Dr Coles does sometimes write on Alemtuzumab on Cambridge web pages.but has other interests besides blogging. However there you have it from the horses mouth..CAMPATHers aren't all quiet

    5. There would be not too much point having too many blogs saying the same thing but I suppose it gives choice where to get information but labs say focussing on repair,would I think get a lot of interest.

  3. Your diagram seems to indicate that a virus directly attacks the oligodendrocyte. Do you have any references for this?

    1. The problem with the virus hypothesis is that they cannot find the same one in all MSers, or can they? If it is a HERV (Human endogenous retro virus) then it is in every cell in the body has them because they are in our genome. It may depends if they made into active virus.

  4. I remember reading that the obly diseases that humans have managed to cure or eliminate are those caused by viruses, bacteria, etc. That's why I really really hope Prof G is right. The Charcot Project is our best chance

  5. I wonder why we think there is one "MS." As my diagnosis was explained to me, it's not this sexual disease or that. It's not lymes disease. It's not testicular cancer or any one of dozens of other possible maladies. Therefor it is MS. MS "explains" the O-bands and lesions. The problem I always have with this logic is it says "It is not a, b or c. Therefor it is D." This logic ignores all other letters, numbers, characters and combinations of all of them. From a patient's perspective, I always thought it odd to have a bunch of symptoms progressing at different rates and responding to different treatments all lumped under the term "MS." Expecting all of MS to fall under any one umbrella, virus caused versus autoimmune, seems an attempt to lock research going down one path instead of two (or more).

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