Smouldering away

S

As you are aware we, or I depending on your perspective, have recently have hit a brick wall trying to convince the MS community that the big unmet need in MS is smouldering disease.

The central hypothesis is that smouldering MS is the real MS. The following YouTube presentation summarises some of the main arguments for the hypothesis.

Your comments will help me make a decision to giving-up working on established MS and to focus on preventive neurology; in particular, preventing MS.

CoI: multiple

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

43 comments

  • Any new direction of research is adventagous especially this one.
    My MS has been smouldering under tysabri 11 years now. I want the fire put out. Can we please switch MS off.

    • Can you please tell more about your disease history and tysabri and other medication experience. My wife is newly diagnosed with MS and was put on Tysabri straight away.

      Sincerely
      Mikael

  • Hi Prof G,

    I think you should focus on established MS; we need leaders in the full sense of the word and not just managers. Prevention is better than cure, but you still need a cure.

    BW,

    F

  • Prof G,

    Great presentation – you’ve convinced me.

    Please stick to tackling MS rather than prevented on. My reasoning is as follows:

    – There are 130,00 people with MS in the U.K. who are all getting worse / will get worse. They need treatments to stop smouldering MS now. Prevention studies won’t help them.

    – Prevention studies will take decades. Having treatments which tackle the real MS will in effect negate the need for prevention strategies – a bit live HIV treatment and some cancer treatment. The treatments become so good that the patient can live a full life.

    – the MS society has a research blog. Prof Coles posted the fallingvlast September Alasdair is ambitious about the future of MS treatment. “I firmly believe we can change the outlook of MS,” he says. “I hope in 10 years’ time, a person will be given a handful of treatments to tackle all the different elements of MS, and they will be offered hope that their life will be minimally affected by the condition.”. This should be the target and there appears to be quite a lot of work in hand to try to achieve this. It will need a concerted and collaborative effort from you and your fellow MSologists.

    – once the real MS is tackled you can put your feet up knowing MSers will not have to face a life of worsening disability and an early death. Prevention will take so long (in terms of testing the possible approaches) that you will be pushing up daisies before the results will be known.

    Good luck in your continuing efforts to tackle the real MS.

  • Really great presentation 👍🏼
    I agree that smoldering or English Smouldering is a more accurate term than RRMS and PPMS.
    It just sounds as icky as it is. That’s no fun. Isn’t it better to check my cratered MRI and say “All’s quiet” while the flames lap at my csf’s edge. Maybe like lava flows into to sea.
    You need a better word. How about calling it a spectrum, a continuum, a gauntlet.
    Maybe keep it as one name, Multiple Sclerosis.
    I really hate describing my RRMS designation as “mild” MS.
    It Is Mild-er. I’m not bed bound, or quadriplegic.
    Now if I knew I had Progressive MS but in a controlled status, would I be more adherent to a Medical prescription? If I go around saying I am mild but inside I’m smouldering, maybe I’ll go without some elements that would prevent Progression, or Advancement, or Flame 🔥 up.
    Now about Biotin. I’m taking hair,skin,nail formula. I think it helps strengthen my connective tissues.Does that increased structure help my framework hold together? Shrinking those spaces where lymph fluids, toxic metabolites sit, irritating raw nerves.
    About MRI. Why use gadolinium at all? Please, please consider that gadolinium Is retained. I believe it crosses over where nerve raw spots are. I wrote Lublin about my receiving 7 Gad doses in 9 years for CombiRx study. I am concerned this possibility is being overlooked.
    Thanks so much for asking people. I think it is time to rethink many aspects.

  • Please, please, please don’t stop work on smouldering MS, established disease.

    My (at least) two decades long MS course has been characterised by slow smouldering. Your presentation makes so much sense to me. It’s like the sun rising finally after a long, moonless night.

    Please don’t give up on people like me.

  • What are the reasons for people not ‘hearing’ / disputing your argument? What is your response to those?

    Either way, I personally think that you shouldn’t give up trying to convince them, and that is because of the reasons another commentator gave earlier AND to minimise the amount of research time and £ wasted by still targeting the inflammatory driven approach. Also – presumably the acceptance of the ‘smouldering’ root would potentially change some of how the prevention work is tackled? So as a first principle relating to causation it also has importance?

    My daughter was diagnosed at age 19, with lesions on optic nerve, brain stem and spine. No new lesions in 3 years on Fingolimod (great) BUT clear degeneration in leg strength and hands etc. Being told that no new lesions is good and therefore no change to treatment is heartbreaking when the deterioration is clear. Then worrying about any impact of rediagnosis to SPMS in terms of limitations to current or future treatment options adds to the sense of being bound by a system/classification/mindset that intuitively you know cannot be right. To then hear your presentation brings science to what we know from our hearts and our first hand experiences. You are our voice – please don’t be silenced, please don’t give up, please continue to build the case, build your evidence and counter the other arguments.

    https://quotefancy.com/quote/758511/Socrates-The-secret-of-change-is-to-focus-all-of-your-energy-not-on-fighting-the-old-but

  • So finally smoldering MS is independent of the ‘type of MS’, cause MS is one disease, and worsening from the begining.
    What can pwMS do now to reduce this effect?
    We have a lot of treatment against the MS related inflammation, but if we switch off it we need add on threapies to
    – protect neurons
    – promote remyelination,
    New answers demand new unmet needs!
    – could pwMS take metformin, clmeastine, lipoic acid etc.?
    Oh i almost forgot: could mastinib be a breakthrough drug or ‘only’ a new brick in the wall?

  • Hello professor,

    We need to find a cure for the disease first and to do that, we need to establish the real cause of the condition.
    As someone who has been diagnosed recently, I need a hope that the cure is in the horizon.

  • Please tackle the hard questions in progressive MS. What is the disease mechanism? Is it fundamentally different? Why it is seemingly unresponsive to DMTs? Is it a disease of failure to repair rather than attack?
    (progressive = no treatment, no MRI monitoring and feeling abandoned)

  • Dear Prof G,
    I watched your presentation with fascination, not that I understood all of it, but it’s sort of amazing to see what I’m dealing with discussed at all. In a nutshell, an MS specialist told me that I do not have MS due to the fact that my lesions smolder rather than scar. I have no brain lesions, but several inside of my spinal cord which have lit up with every MRI over five years.

    You are on to something big. Please don’t give up. I have been offered no treatment other than steroids and I have no idea what to ask for. It seems like the medical community was stymied and I fell through the cracks.

    Keep going, sir. Please.

    Allison Hawley

  • I can’t say whether the MS world would be more impacted by prevention or getting the focus shifted to smoldering MS. I can only say my own experience. I was diagnosed with MS about a year and a half ago. I have had progressive worsening for probably about 15 years, but most of it was so subtle it was very hard to see. I have never had a relapse, or anything I would’ve been able to identify as a relapse. My MRI shows extensive demyelination, but few focal lesions and thing active. At my last scan my MS doctor told me the scan was stable and acted like that was good news to me, and said the ocrelizumab was working, making noises like everything was going to be OK because the drug is doing its job.

    I don’t personally see a reason to be bullish about my brain. My tremor continues to get worse in my dominant hand and both of my hands get weaker and weaker. My foot drop gets worse and it becomes more difficult to walk. My cognition gets worse, and I have a harder time keeping a hold of my emotions . My speech and swallowing get very subtly worse yet the gastroenterologist and ENT doctor find that my swallowing looks just fine .

    Doctors have nothing to offer me right now, but they think they are giving me great help. I want something that Will help me preserve the brain that I have right now, and I don’t think that is going to come from pharmacology. Instead I take care of my own brain. I swim because when I do it I get great exercise and my body feels almost normal. I read because it’s great brain exercise, although sometimes I struggle to follow complex plots. I sing because I love music and everything music can do for you. I work on learning piano pieces, although it is painfully slow going and my right hand often doesn’t cooperate . I do lots of other things, including doctor appointments, but I think the doctors appointments are the least helpful to my overall health.

    I am sliding down a mountain right now, and would love for there to be a tree branch I could grab onto to stop the slide. It would make all the difference to me. But right after I was diagnosed, I found out my then 12-year-old daughter had mono and we live in Boston, and so I worry about her brain all the time. I think that both trying to keep her from getting MS, and trying to preserve her brain function if she does end up getting MS, both of those are the most important things to me

  • Please continue focusing on smoldering MS. I am influenced by my history:

    • 1st MS event at 22 years, with “full” recovery within three months.
    • A handful of brief relapses for the next 15 years, always seemingly recovering fully.
    • Then a 30-year symptom-free period with no relapses. I appeared “normal” and NEDA externally, despite MRIs showing probable MS plaques.
    • Only to then, as my age advanced into my 60s, start showing evidence of ambulatory and equilibrium difficulties, forcing me to start using a cane and rollator.

    I am a sample of one, I realize. If I had not been influenced, however, by my 30-year symptom-free period into believing I had somehow overcome MS, I would have planned differently my finances, accommodations et al. Unfortunately, MS had been smoldering all along. So keep alive that definition of the MS condition, please.

  • Prof G,

    Keep up your current work.

    However, aren’t you falling into the same trap as those who have focussed on relapse and focal inflammation? Smouldering MS is just a response to something in the brain. Tackling smouldering MS and SELs doesn’t tackle the issue of what is in the brain which leads to smouldering MS and SELs.

    Until the virus (ebv) in the brain is eradicated, the responses – smouldering MS, SELs, focal inflammation, relapses – will continue in one form or another.

  • I’m perplexed! How could anyone watching your presentation persist with thinking that smouldering MS is not the reality, and that there remains legitimate scientific endorsement for applying the Lublin classification!??! Is it simply the case that human beings are appallingly slow at rejecting established norms – look how many decades it took for it to be accepted that cigarettes are bad for your health.

    I’m another one of those for you remaining in the tackling MS camp, as any change of the ways in which MS is treated and managed will need those such as yourself to keep slogging away at the smouldering MS message.

    Aaron Boster said in a vid recently that sadly he doesn’t see a cure for MS happening during his lifetime. As mentioned previously on this site, we know that there are many chronic conditions such as Type 1 diabetes that are managed life-long, without people living with the prospect of a cure. So much of your presentation referenced things such as neuro protection, exercise etc and all the relevant studies. As a cure may prove elusive into the distant future, this is also where your focus and energy are so well placed: developing all those ways to enable people with MS to live well with a disease that is effectively managed.

  • First off, who is your audience in this presentation? It’s worrisome that I completely understand or already know (to use the term loosely) everything you’ve said. If you’re speaking to med professionals, shouldn’t it, to the average Joe, sound as though you are speaking in tongues?

    Isn’t the term “smouldering MS” just highlighting the original insult in the cascade that obviously isn’t addressed w immunomodulating meds? How is there any resistance to this concept? There is a cause for MS and it’s dancing around, dodging drugs, blowing raspberries, and flipping the bird at all of us! Maybe your term isn’t clear enough?

    “Know thy enemy.” You’ve got to find the cause before you can be confident in your ability to prevent MS. So…stick with working on existing MS. It’s better for me that way too. 😀

      • But what can neurologists (or patients, or caregivers) really do with that info? The cause is still unknown by the masses. We’ve no approved drugs for remyelination yet (though mine happily prescribes clemastine “for my allergies”).

        Neuros surely must already recommend exercise of mind and body…neuroplasticity has been a big thing since early 2000’s at latest. Once new treatments hit the market, they’ll recommend, right? I think, in practice, their direct guidance is constrained by regulation, ethics, and fear of malpractice suits. You’re a neurologist. How do you treat smouldering MS?

        Or am I getting this all wrong? Do you want folks to join some brigade to rally pharma to come up with treatments for smouldering MS? This argument is really intended for pharma/researchers?

        What do you want from this effort?

  • This is an awesome presentation. Thanks for putting it up on YouTube!
    I think that continuing to ask the tough questions about the data and what they mean for MS is crucial.
    There are plenty of other experts and specialists following their other theories and research. Trying to figure out what works and why helps keep the science in this battle among all of the conflicting interests.
    It is important to patients.
    It is important to researchers.
    It is important to clinicians.
    It is important to policy makers.
    It is important to many many others.
    This is an example of what is so Great about this blog and all the hard work that you guys are doing in your real jobs.

    I’d like to see more of these clear video and slide deck presentations. I appreciate that you often post the slide sets, but a lot is missing without the presentation that goes along to explain the slides. I am sure that it would be more obvious to professionals, but I for one can sure use a clear and candid explanation.

  • Loved that presentation! Crystal clear 😊

    Re
    have hit a brick wall trying to convince the MS community that the big unmet need in MS is smouldering disease

    Brick wall? Think I remember reading something but couldn’t find the post? Presentation doesn’t sound like a brick wall to me…. too many pwMS need you

    🤔 Aha think of it as platform 9 3/4

  • Dear Prof G,

    Yes. I see it as a two part problem:

    Prevention
    Early detection

    I think that we should research more into an MS test, some way to detect MS very early. Some method of detecting a signal from a plague, just enough of a signal to determine if someone should receive an MRI.

    Prevention of acquiring MS is a much more difficult problem, without a known cause, how can you prevent? It is a worthy research area. Do we learn more about EBV?

  • I’m quite new to MS, but in the past 6 months every single place where patients talk online, as you write here and in your talks, there are so many people who write they are still having symptoms or feeling worse despite being on effective treatment. It blows my mind a bit that you say the MS community won’t accept this? That must be incredibly frustrating. However not that surprising I suppose as people are people and there’s incompetence everywhere :’)
    Is there any other explanation for that aside from smouldering disease?
    I would vote for smouldering MS. But it’s not a very informed vote because I don’t know much about the work that is happening on the prevention side.

  • Please keep going on converting the established dogma. We saw the same delay in uptake moving from chemotherapy to effective immuno-oncology agents. It takes vision and time. You just haven’t hit the Tipping Point yet. But you will.

  • How do you suggest we tackle smouldering MS? What do you think is driving smouldering MS? Do you still think is could be viral e.g. EBV/HERV?

    • I don’t think anyone argues it has some benefit in progressive MS, however there are aspects of MS that do not readily respond to this and therefore the people who benefit best are treated early. However the biology suggests that processes continue that HSCT does not currently touch so do not expect miracles. Keep your expectations grounded.

  • Oh Please keep on working on smouldering MS. There is a huge need for this. So many others working on prevention and cure

  • I agree with some of the other voices that point out that until we know the cause of the disease we can’t hope to prevent it. I think investigating the mechanisms involved in ‘smouldering ms’ are likely to help understand the root cause. So I think you can work on both.

    Please keep up the great work! Without people like you who keep bashing the brick wall it will never come down. I’m sure this takes a toll on you but those like me who have ‘smouldering ms’ want and need you to not give up.

    I appreciate the work you do as do many do many other patients.

By Prof G

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