Tackling progressive MS

Tackling Progressive MS is a priority. ECTRIMS had a meeting on this subject and they have done a special issue on this.

Here’s a list of several papers on this subject.

The International Progressive MS alliance has made these open access so please read as they may be of interest.

Progressive MS trials: Lessons learned.
Mult Scler. 2017 Oct;23(12):1583-1592.

Advancing trial design in progressive multiple sclerosis.
Fox RJ, Chataway J.Mult Scler. 2017 Oct;23(12):1573-1578.

Advancing trial design in progressive multiple sclerosis.
Miller DH, Thompson AJ.Mult Scler. 2017 Oct;23(12):1571-1572.

Barro C, Leocani L, Leppert D, Comi G, Kappos L, Kuhle J.
Fluid biomarker and electrophysiological outcome measures for progressive MS trials.Mult Scler. 2017 Oct;23(12):1600-1613.

Wolinsky JS.Patient selection for trials.Mult Scler. 2017 Oct;23(12):1636-1641

Zaratin P, Comi G, Leppert D.‘Progressive MS – macro views’: The need for novel clinical trial paradigms to enable drug development for progressive MS.Mult Scler. 2017 Oct;23(12):1649-1655.

Moccia M, de Stefano N, Barkhof F.Imaging outcome measures for progressive multiple sclerosis trials.Mult Scler. 2017 Oct;23(12):1614-1626.

Lassmann H.Targets of therapy in progressive MS.Mult Scler. 2017 Oct;23(12):1593-1599

Ontaneda D, Cohen JA, Amato MP.Clinical outcome measures for progressive MS trials.Mult Scler. 2017 Oct;23(12):1627-1635.
First thing: What have I done to not get an invite :-(?

Maybe I am too frank!

What do these papers say:

There are three broad areas: systemic inflammation, compartmentalized inflammation and non-inflammatory neurodegeneration. They say “anti-inflammatory treatments are unlikely to be beneficial in this (progressive) stage of the disease, but neuroprotective and repair-inducing strategies may still be effective.”

So maybe that’s the problem. DrK would say “nonsense, wake-up and smell the roses people”.  

They will say “this is why we won’t support #ChariotMS, because it won’t work”. 

I say “Is there ambition to try and make a difference?” We think we need to deal with inflammation that occurs throughout MS, and likewise we need to protect and repair throughout MS

Last Years Burning Debate @ ECTRIMS
Gave us a Flavour of What Some of our Colleagues 
Think about Trials in Advance MS

If you are sensitive to views, that you don’t want to hear 
Don’t listen or press the triangle!

What do you think?

About the author



  • As someone with PPMS I am not excited by anti-infammatories. I am fed up of neurologists, researchers continually flogging this very tired old horse. Neuroprotectives are required to make any real headway. But that's not so easy / convenient.

    • Neuroprotectives are needed on top of an anti-inflammatory and this is the horse that needs flogging.

      The post above was edited to remove the bit said by DrK, at the time he was looking at scans from someone with advanced MS and was counting the active lesions one by one by one by one by one. This person neds an anti-inflammatory

    • Maybe neuroprotectives stop the inflammation? Do you know whether they do or do not? No – no one does yet, because there are still no neuroprotectives. But still the organ grinder goes on – anti-inflammatories, anti-inflammatories, anti-inflammatories, anti-inflammatories, ad infinitum. And the monkeys dance, and the dollars fly.

    • Do I know….for some yep

      Some do and many don't.

      Sodium channel blockers were anti inflammatory and that is why the progressive trial failed. It removed swelling making people think the brain shrunk.
      But we showed twice that they save nerves.

    • Excuse me – where are the trials looking at neuroprotectives as an alternative to immune system annihilation?

      Of course anti-inflammatories work in many people – with the right kind of inflammation. In these people, the risk/benefit ratio of such therapies are in favour of treatment. But what about those with proportionately high levels of neurodegeneration and low levels of systemic inflammation?

      You talk of dogma, yet what are you mostly promoting/offering? The same old anti-inflammatories. Nothing new for neurodegeneration/neuroprotection, nothing to target the root cause of MS. Not yet – though maybe you will one day. I hope so.

    • Well off the top of my head there was the Lamotrigene trial (failed), Cupid trial (positive in a sub-group of pwMS, The Simvastatin phase II Statin trial (positive now going into phase III trial) and Phenytoin in optic neuritis trial (positive). The Barts MS Proximus trial, (Oxcarbazepine study) is ongoing.
      So, progress is slower than we'd like due to pharma being reluctant to get on board but there is progress.

  • These papers are in contrast with team G view of trying one more round of anti-inflamatory drugs on wheelchair pwms
    Maybe you will need a burning debate in the Ectrims regarding team G views and theses papers views


  • Inflammation, with current data using anti-inflammatories siponimod and ocrezulimab, reduced progression at best by < 25%. This means > 75% of the answer is still missing in terms of treating progression and it hopefully lies within neuroprotective, remyelination and neurorestorative therapies. Why these therapies were not researched concurrently with anti-inflammatory therapies is beyond maddening.

    With all the billions made by pharma and billions raised by MS Society, one would think we would have one meaningful treatment approved by this time but I guess not. I guess researchers are just figuring out how to do a proper progressive MS trial at this point and figure out proper endpoints and this means a efficacious approach progressive MS treatment is still decades away.

    • “Inflammation, with current data using anti-inflammatories siponimod and ocrezulimab, reduced progression at best by < 25%. This means > 75% of the answer is still missing in terms of treating progression and it hopefully lies within neuroprotective, remyelination and neurorestorative therapies.“

      Hopefully yes, but in the foreseeable future it is unrealistic to expect that once a significant number of axons (say 50% in the spinal cord) has been lost, you have the same chance for recovery as in somebody who starts treatment – any treatment – with only 10% loss. The 25% difference becomes 45% when you look at upper limb function as your outcome, and who knows may become even more if you follow up people for longer, as the maximum duration of trials is currently 3 years, and with therapeutic lag this may just be the time when treatments take full effect.

      I agree we could be significantly further than we are now had a dominant "progressive MS expert opinion" been taken to task earlier by those who keep listing to claims – based on a dogmatic misinterpretation of the evidence – that inflammation plays no role in progressive MS.

  • Siponimod, Ocrelizumab and Cladribine (why they don't test Cladribine in progressive MS?), associated with possible neuroprotective agents: sodium cannabinoid blockers, alpha lipoic acid, cysteine, and yes, Clemastine. Now you have to do the tests for know if they will work, if they don't test how and what will be known if they have or don't work?

    MD I still have that doubt about Clemastine and Alzheimer's.

    As far as I found Clemastine is anticholinergic of 1st generation, then the risk of leading to dementia is higher.
    So how would the use of it in remyelination in MS?
    I even saw researchers about the use of Clemastin in ALS, but they didn't talk about dementia as a side effect.

    • "Why they don't test Cladribine in progressive MS?"

      Who is "they"? For big pharma the answer in one word is: patent-life. – Another reason why ChariotMS could make such a significant difference; results (and adoption) would stay with pwMS and their MS teams long after big pharma has left the arena.

      "I even saw researchers about the use of Clemastin in ALS, but they didn't talk about dementia as a side effect."

      Remember how different the life expectancy is with MND compared to MS, and so is, as a result, the risk-benefit analysis.

  • Just a comment/my experience with PPMS…..

    I have what is termed PPMS or as you say 'advanced MS'. I am mostly in a wheelchair, with an EDSS of 7.5, but still work full time (I use my grey matter, what is left of it). I often talk to my neuro (an MS specialist) and ask – what is out there to help? to which the response is "nothing…..I am sorry".

    So following some of my own research, I decided to self medicate with steroids (Prednisolone). Shock horror! what a difference a pulsed treatment of 30 mg per diem taken over two days makes! Got up and walked (with crutches) around my garden three times! Not possible on 'normal days'

    I have correlated my increase in mobility with taking the steroids on 95% of treatments. The only time it did not work was when I had a bad UTI. So are we missing a trick here? My neuro refuses to be drawn on it? Why? What is happening? Is it a well known effect that has been kept in the dark? It may not by a DMT per se, but it certainly improves my quality of life.

    Sod the side effects if I have a better quality of life – This is what I have noticed from my engagement with the medical profession – too afraid to take risks and do not take the patients quality of life into account or are swayed by pharma or those 'that know the price of everything and the value of nothing' (to paraphrase)- NICE. After all, I pay pence for my tablets.

    And yes, I do know what I am doing – I am a Scientist with a clear mind, albeit a very belligerent one 🙂

By MouseDoctor



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