Remyelination: why have we failed?


Barts-MS rose-tinted-odometer: ★

I sit on several steering committees and advisory boards for projects that are exploring remyelination or recovery of function as a treatment strategy in MS. Doing this allows you to think or groupthink, which has prompted me to consider whether remyelination in MS is necessary or not. I have been scratching my head about why in 2020 three remyelination strategies failed.

  1. High-dose biotin (MedDay) – Effect of MD1003 in Progressive Multiple Sclerosis (SPI2) ( Identifier: NCT02936037)

    Primary outcome: Proportion of patients Improved on either the EDSS or 25TW
  2. Bexarotene (Cambridge University) – A trial to determine bexarotene’s safety and tolerability and its ability to promote brain repair in patients with multiple sclerosis (EudraCT number 2014-003145-99)

    Secondary or remyelination outcome: Change in mean lesional MTR between month 0 and month 6 for lesions selected for each patient.
  3. Opincinumab (Biogen) – Efficacy and Safety of BIIB033 (Opicinumab) as an Add-on Therapy to Disease-Modifying Therapies (DMTs) in Relapsing Multiple Sclerosis (MS) (AFFINITY) ( Identifier: NCT03222973)

    Primary outcome: Overall Response Score, a multicomponent score based on 4 components: EDSS, T25FW, 9HPT in the dominant hand and non-dominant hand. 

Have we the MS community made a fundamental mistake in assuming that remyelination is an ongoing persistent problem that needs fixing in MS? Have we got the biology wrong? Is biotin-dependent mitochondrial dysfunction and biotin-dependent remyelination pathways a problem in MS? Is the activation of retinoid X receptors (RXRs) to promote remyelination the correct target in MS? Is the inhibition of an inhibitor of remyelination with opicinumab (anti-LINGO-1) sufficient to promote remyelination across the central nervous system? At least with anti-LINGO-1 or opicinumab, there was proof of biology, i.e. the drug did improve conduction speed in demyelinated optic nerves. 

Were the trial designs correct? For high-dose biotin, the population of pwMS was quite old with a lot of disability. Maybe the population was too old and hence ageing mechanism prevented any recovery of function from being detected. Maybe there was too much axonal or nerve loss and hence remyelination was doomed to fail.

Maybe focusing on the individual MS lesion with bexarotene using MRI techniques is too fickle? It is clear that in the bexarotene study there were too few new, presumably actively demyelinating, lesions to generate a signal. 

The overall response score in the opicinumab trial may not be good enough to capture the recovery of function due to remyelination. The idea of using a composite score to detect recovery of function makes clinical and biological sense. However, using the limbs as the main read-out may not be sensitive enough. What about vision, cognition, balance, bowels, bladder, fatigue, etc. Do we need a better outcome measure? Do we have to go back to the drawing board with our clinical outcome measures?

Or is the answer staring us in the face? When you treat MS early with the big guns, i.e. alemtuzumab or HSCT, it is quite remarkable how many pwMS have spontaneous recovery of function. Are alemtuzumab and HSCT doing something fundamental to the pathogenesis of MS that then allows for spontaneous recovery of function? Are we curing a proportion of people with MS with these treatments?

One of the latest theories that is being tested in MS is that because of premature ageing and senescence the oligodendrocyte precursors and oligodendrocytes (myelin-producing cells) can’t function properly. The solution is to reprogramme them, i.e. dial back the ageing clock by using diet (caloric restriction, intermittent fasting or ketosis) and/or medication (e.g. metformin or fumarates) before hitting them with drugs to stimulate myelin formation. The latter is backed by animal data, but will it work in MS? Possibly; however, this is based on the assumption that the tools we have for measuring remyelination in pwMS actually work.

The danger with all these strategies is tossing the baby out with the bathwater, i.e. once a trial is negative with a compound it is very rare that the community goes back to the compound or biology. So we need to be confident that our methods are sound and reliable. I am not sure we can be that confident after the three failures above. 

Another aspect that is lacking in all our trials is neurorehabilitation, i.e creating the biological stimulus to promote recovery of function. Nobody would perform a spinal cord injury recovery of function trial without active rehabilitation on top of the treatment being tested. The latter is backed up by sound science and compelling animal studies. Why do we in the MS community expect spontaneous recovery of function without rehab? If you don’t use it you lose it! To encourage the recovery of function you need to stress the pathway. I thought this concept would be a no-brainer, but I have yet to convince one Pharma company to add-on a rehab programme to their recovery of function trials.

Maybe instead of trying to promote remyelination and recovery of function in pwMS, our aim should be to treat MS effectively early on, i.e. to prevent the need for remyelination therapies in the first place? The question is how do we get the wider MS community to promote the use of alemtuzumab and HSCT, or similar agents, as the default first-line therapy for MS? Some of us have tried, including me, but have failed miserably with this seemingly easy task. By the time most pwMS get to alemtuzumab or HSCT, they have so much damage that they need restoration therapies. 

As we think we now know the potential cause of MS trying to put out a fire without correcting the upstream pathology is folly. Therefore maybe we should only be trying remyelination and neurorestorative therapies in people who have stable fixed deficits, with no ongoing evidence of any inflammatory disease activity, post alemtuzumab or HSCT? The irony of letting pwMS become disabled before being treated with alemtuzumab or HSCT is inadvertently creating a trial-ready population of subjects for remyelination therapy trials.

I encourage thoughts or counter arguments on the above. Let’s have an open discussion and debate on the points I have raised in this post. I think we need to answer some fundamental questions about remyelination and neurorestorative therapies before we spend more money on futile trials and throw the baby out with the bathwater. 

CoI: multiple

Twitter: @gavinGiovannoni                                              Medium: @gavin_24211

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.


  • Just to say I am tired of COVID-19 and feel the urgent need to move beyond the endless news and research cycle of COVID-19. It is time to focus on the ‘Real MS’ and ‘MS Prevention’. Do you agree?

    • I’ll agree once we’ve all been vaccinated and can start getting back to semi-normal 😉

      But you’re right, just because of Covid-19, MS doesn’t go away…

    • Prof G,

      Apologies for long post.

      I totally agree with your point about Covid 19 and the need to move on to focus on MS. The devil finds work for idle hands to do and I suspect that many researchers in the field of immunology (including neuro-immunology) have pumped out research papers on Covid 19 to (1) keep their publication count up and (2) give them a break from the really hard stuff ie for neuro-immunology working out what MS is.

      After c.15 years with MS I’m a grouch. I make no excuses. A female friend who was diagnosed a few years before me and in her mid 50s is now in an electric wheelchair which she operates with her two functioning fingers. I find this unacceptable in the 2020s. I was listening to a phone in radio show last night and a man called in to say his vulnerable wife had not been contacted about getting a jab. He said that she had had MS for 30 years and had been bed ridden for the last five. Again, I find this unacceptable – that people are being left to wither away in their bedrooms as no treatments are available for progressive MS (I know you will say some treatments are available for progressive MS, but in reality they don’t stop MS or impact on what’s really underlying progression).

      The three remyelination trials you cite are just the tip of the iceberg. Over the last 15 years I’ve lost count of the various initiatives run by MS societies to “stop MS”,
      “Roll back the ravages of MS”….. I’ve lost count of the neuroprotective trials that have failed or the trials to repair damage (I recall a stem cell trial in Bristol some 12 years ago with “tantalising” signs or repair – I’ve heard nothing since). Don’t even get me started on the NMSS’s Promise 2010 initiative.

      The government during Covid 19 has been accused of “over-promising and under-delivering”. This is a perfect summary of MS research (all MS research across the world).

      The fundamental issue which MSer researchers / the MS research establishment has to accept is that the understanding of what MS is and what drives it is poor at best. In my 15 years with MS it’s gone from autoimmune, to inflammatory, to inflammatory leading to neurodegeneration, to neurodegeneration causing an inflammatory response. It’s been a disease of white matter, then grey and white matter. Myelin as the target of attacks, inside-out disease, outside-disease, driven by a virus….

      Usually knowledge and understanding builds over time, but with MS previous dogma is slain, new ideas are put forward which subsequently become dogma which are slain… It’s Groundhog Day.

      Apologies for the long post, but I think MS research is a mess. With an organ the size of a small cabbage and the unbelievable advances in technology, we should be further along! Unfortunately, MS is a cash cow for pharma, it is a never ending gravy train for MS researchers / doctors (conferences, steering committees, consultancy work), and a bottomless pit of topics for PhD students. Why rock the boat or bite the hand that feeds you?

      Before any more work is done on remyelination and restoration work, there needs to be a universally agreed understanding of what MS is and what drives it (ie a definitive answer eg MS is caused by EBV which leads to smouldering inflammation…). Then work to address the disease can start. For too long the approach has been the other way round ie here’s a drug which might help, let’s do a trial.

      Please don’t write off patients who won’t benefit from Alemtuzumab or HSCT. These are the patients that need the most help in terms of treatments that stop progression/ promote some repair.

      Thank you for all your efforts. Use the Covid-19 ad “act like you’ve got it”. If MS researchers adopted this approach we might start to see advances.

      • Well said.

        I find it incredible that humankind can develop multiple effective vaccines for a coronavirus in under a year and land a rover with absolute precision on Mars, yet, talking to my neurologist, what is there for PPMS?

        Nichts, nada, zilch, big fat nothing.

      • “Act like you’ve got it”.

        That’s potent. I definitely agree with you – I’ve had it 20 years now. It’s not just the researchers, it’s those directing it and paying for it who need to act like they’ve got it.

        Other things that have come out of Covid-19:

        Development can be quick if there’s money to pay for it and a fear of loss (from government) of staring down the barrel of millions dead.

        mRNA therapy works and gives medicine tiny protein factories in patients to pump out the proteins needed to invoke immune responses. This will revolutionise medicine,

        An obsession with “where it came from” and “understanding it in full before trying to treat it” leads to suffering. After all – the pandemic would’ve killed far more and damaged far more if we’d insisted on that. And with MS – the old practice of waiting for a second relapse before treating it at all… all that time wasted, years and years of brain destroyed… time = brain

        I agree – don’t write off patients who won’t benefit from Alemtuzumab or HSCT.

        But we also need to understand there are deeply embedded vested interests at work here (you mention them) – which mean that your drive for universal understanding of “what is MS?” – that could take years for consensus to be reached and “time = brain”. They need to be looking at treating ALL of MS, not just “relapsing remitting” or “primary progressive” because they don’t exist. There is just MS. But then you couldn’t get orphan licensing for your expensive drug to treat one sub-type. All of MS is too big and therapy efficacy ranges too much depending on stage of disease and extent of damage / alteration to the immune system. And that’s another area to look at – when you stop the disease, how do you reprogram the immune system? mRNA treatments?

        I think we have to accept the fractured model as the reality for now and try to persuade MS funders to pump the money into the research that most closely matches with the likely model (EBV and / or other virus leads to some more steps leads to smouldering inflammation leads to MS).

        • I agree with all the opinions expressed, but when is everybody going to stop talking about PPMS, RRMS and SPMS as if they’re all different conditions? We’ve seen on this blog that they are artificial constructs created so that pharma can make more money out of this illness. It’s all MS with various degrees of activity and it’s all driven by the same disease process (probably EBV +/- some other retroviruses).
          The one comment that concerns me is about the pwMS who hasn’t had CoVID-19 vaccination handed to her on a plate. Why hasn’t somebody contacted the NHS for her and requested it? It’s available and she meets the JCVI criteria. We can argue about the pro’s and con’s of various vaccination intervals, but she should be getting her first dose by now, and if she can’t get to a vaccination centre, her GP should be going out and giving her the AZ jab. If this doesn’t happen, somebody should complain to her CCG.

      • dear SID,
        I won’t never forget your feelings and the facts you said in this post…
        in every second of my research on PPMS, I will think and consider all you mentioned..
        i completely understand what you are saying as my mom suffers from PPMS and there is nothing more painful than watching your mom are getting worse……
        So i hope i will do my best to find out sth “really helpful” for you…
        (i am now bachelor student of biotechnology in iran
        and i’m going to be a PPMS researcher…)

      • Omg!! I totally agree my husbands cognitive impairment is bad I have watched it decline over the 20 yrs we have been together, I read studies upon studies and its all for the scientists to get funding to try this drug or that drug as you say with no really outcome. I ask the neurologist if there were any studies in the UK using the tesla 7 mri looking into grey matter(as they just concentrate on white matter lessions which have stopped happening for my husband but he’s still declined) he said why we know its shrinking we don’t have a magic pill for it, its just what happens!!!! I have never felt so much rage. To me the brain is so clever if we could tape into the big part of this muscle none of us use then wouldn’t people with ms have their own back up to switch over too??

    • I absolutely agree. every second is important for people with MS especially those with PPMS! as they are getting worse by the time!
      So researchers like me should take the responsibility of our jobs and know that all of PPMS patients have the dream of being healthy just by helps and efforts of researchers …

    • Seeing how interested (NOT) the general population is for prevention of much more widespread diseases (diabetes, heart disease…), I would focus on a cure.

      Of course as PwMS that would also benefit me more 😉

  • I think the logical extension of your argument is to stop all treatment for pwMS and concentrate on a vaccine to prevent it occurring in the first place.

    As a pwMS I was unaware of the debate within the research community about drugs of choice. I dutifully appraised myself of the state of the art and the NICE guidelines. I chose the best of what was available to me (Tecfidera). From the information on the effectiveness side effect trade off I would have chosen Ocrevus, but this was just before The stately dance between the manufacturer and NICE had been concluded so it was not available and would probably not have been accepted as my first option.
    The choice of metric to determine severity of disease is debatable and the impact of non drug interventions such as physiotherapy poorly understood valued and researched.

    • Yes exactly they should be able to screen for the gene and have a vaccine ready to give any who are positive with the gene to stop any start or advancement. How did the manage it so quick for covid it effected the economy!! If the whole world was to suddenly develop ppms there would be a vaccine tomorrow!

  • Or perhaps the fundamental flaw is that remyelination only works when you stop destroying myelin?

    We know that patients on CD20 therapies still experience deterioration / disease progression. It’s slower but it’s still going on.
    We therefore know that the classic markers of the disease – the sclera themselves – are a symptom not a cause. So episodes and MRI activity, whilst extremely important, are only part of the picture.
    You have mentioned how further activity can be seen on higher resolution MRI scans – the black corona around the seemingly inactive lesions showing the MS smouldering away.

    You’re the smouldering MS guy. You already know the answer. Put out the fire before trying to rebuild the wooden house with the straw roof…

    There is already research showing oligodendrocytes as a possible culprit – that they can promote myelin regrowth but can also be reprogrammed to attack myelin even when other immune responses have been withdrawn by CD20 treatment. Could this be because they’ve spent the last however many years being told that “myelin is bad”? Perhaps they too need some retraining to switch them back to protecting and regrowing myelin?

    I’ve taken your advice onboard. I’m cycling between 10 & 15 km, 4 times / week. I want to get it up to 30km daily but being middle-aged and border-line obese I don’t want to damage anything on the way there and have to stop. I’ve also started myself on metformin and alpha lipoic acid this week – which seems to reduce my stamina but I’m sure I’ll get used to it (I’m in Spain and seem to be able to get metformin OTC in pharmacies).

    I’ve already seen benefits in the 3 weeks since I started – my back ache has gone, my knees no longer hurt, I’m a couple of kilos lighter. But I reckon it could be 2 or 3 years before I start to see any noticeable benefit to lesions. My goal is to reduce one specific lesion / scar that’s reduced function in my right hand so I can no longer play music – my lifetime’s passion. So 2 – 3 years of work to try to get that back seems fine if I can spend the rest of my life happily noodling away on guitar.

  • Once in awhile I see a title and have to stop what I’m doing and comment.
    It wasn’t a surprise, remyelination failure by humans.
    I always feel the same reading any research on Multiple Sclerosis. Me, Once a Neuro Nurse, eager to help my patients get through high dose steroids after an exacerbation. MS 1980-ish.
    No DMT’s. None, Not a one.
    Here come Mrs. Jones again….she can’t walk now.
    Admit 5 days then to nursing home for rehab, she can’t handle much therapy.
    Today, I got my old school Copaxone shot out to warm up. Often I think of Dr. Panitch who I grew to love for his love of beating the MonSter. He invited me to the CombiRx study when diagnosed in 2007. I was randomized to Copaxone only arm but had flu like symptoms with the weekly placebo Avonex shots. The mind Is powerful. I do think Copaxone offers the Proteins needed to bathe my nerves in soothing broth. The give and take, yin/yang, Flowing. Nothing is static.
    I think remyelination is Healing the Sheath.
    Healing over scarred patches like a scab on a wound. Protective. Keeps rawness from spreading while the organism gets better, stronger.
    Forget all your fancy mouse 🐁 drugs.
    Think Vitamin needs, food for healing nerves.
    How to remove toxins?
    Prevention is key.
    One element is to look at toxins the patient is exposed to.
    Particularly Gadolinium. I believe it may do more harm than good.
    Do little pieces of Gad do damage to the scarred places that light up on MRI?
    Lastly, I recently started PT for my flat feet.
    I am truly amazed at what foot exercises are doing for my balance, walking, knee pain.
    Maybe this time I’ll keep doing her exercises after I’m done.
    Thanks for listening 😎

  • Morning Prof,

    Good to see you back in the non-covid saddle. I know this post is primarily about remyelination therapies but as you say, the best approach may be to remove the need for them through early treatment with Alemtuzumab or HSCT. This is clearly a common theme on a number of posts and has left those on CD20 DMTS (as well as others) with itchy feet. I would be keen to see a post / debate on how PwMS can actually gain access to these therapies and the potential pitfalls of doing so. I am researching my own treatment options and so i am a member of a number of facebook groups. The prescription of DMTs amongst different trusts seems to vary widely. It appears that some patients are still being offered Alemtuzumab first line. The bar is high for HSCT and the wait times are long. This prompts a number of patients to seek treatment abroad. MD2 considers this unwise. However, it appears equally unwise to become a sitting duck on a daily injectable. The stress that is caused by fighting for treatment, scans, attention can exacerbate symptoms, cause relapses leading many patients to give up / settle. Covid is complicating the situation for the IRTs and a number of patients may be missing the boat as a result. If HSCT and Alemtuzumab are truly the best fighting chance then please tell us how to get into the ring

  • This is quiet annoying to read i wont lie, when i was first diagnosed i asked to be treated with high efficacy treatment but was only offered the crab drugs by my local area neuro. Unhappy with this i moved myself to a specialist at one of the london hospitals at this point i had three mris in the space of 8 months and had new enhacing lesions on all of them aswell as dramatically worsening symptoms. After speaking with my now specialist neurologist he agreed that i would be perfect for hsct or lemtrada but was not allowed to use it so even though i had a high jcv level the best i could be offered was tysabri. When i questioned why i was told it was due to safety guidlines set by the goverment and nice, well when i contacted the government and the health secretary they pointed me back in the direction of the nhs who then pointed me back to nice who dont respond to the public. My question is and always will be why are these people setting what drugs and treatments can be used and telling us we have to sustain more damage and accrue further disability before we qualify for more efficacious treatment? Why are we losing quality of life (which we get one of) because we are not deemed disabled enough to qualify for irt’s that could potentially give us long term remission ? Its inhumane they wouldnt do it with any other disease ! If thats also your opinion are you actively doing anything to bring about change to the treatment algorithm ? If so what ? There are more than enough studies out there to prove the case for early aggresive irt treatment have you taken it to the right people that joe public have no way of contacting ? Why dont you organise something or ask for help organising something with the ms community to make a point that would bring about media attention and therefore force change ? No one cares about the odd person here and there paying thousands to go abroad and get hsct thats obvious but what about 2000 people that are active on social media marching on downing street ? I thinl that would get attention ! How do you change something that no one cares about unless their in the position? If history tells us anything its that the goverment and nice will listen if enough noise is made !

  • Hit it hard and fast as soon as diagnosed. I have been saying this since the day I received my diagnosis in 2015 and my neurologist just insulted and patronised me, refused my request for Alemtuzumab and refused to believe my MS was anything other than mild. Sadly I was immediately proved right and deteriorated from edss 1 to 6 in 12 months. I’m now £50,000 poorer having had to pay privately for timely HSCT and stuck with serious disability, unable to work again, ever. On the scrapheap before 50 !

    In all likelihood, aggressive treatment when i asked for it would have minimised my edss and left me with a quality of life better than permanent lockdown. I’ve been stuck in bed for weeks recently because of the cold and damp weather aggravating my symptoms. I can only dream of remyelination treatment which might ease pain and fatigue. My mitichondria clearly need help either to make energy or to get it effectively to the rest of my body. Maybe they’re swamped by my cholesterol that jumped massively at the same time I transitioned to SPMS.

    It is more than time that MS patients were treated ethically and with respect. Frankly many patients aren’t even treated at all. A friend of mine died aged 38 just 2 years ago without ever having been prescribed a DMD despite multiple hospital admissions over 3 years since her diagnosis. If you can actually drive for early, highly effective treatment Prof G, that would be a legacy every person with MS would thank you for.

  • I don’t normally comment on ProfG posts, but I want to throw in a few ideas here, about where we go wrong.

    Looking at the data, the biology and the trial design. We have never shown that we can remyleinate an established chronic demyelinating lesion in animals. We show agents can remyelinate a lesion (quicker) in animals that will naturally repar without any treatment anyway and then go to the hard study in humans, with outcome measures that may not be as specific for repair as we are led to believe.

    At the end of the day companies will do what they want to do irrespective of what you may think

    (a) Biotin where was the evidence it is a pro-remyelinating drug. It was first sold that it was a neuroprotective drug. The benefits were almost instantanious suggesting that it was unlikely to be neuroprotective effect. The rapid change in symptoms suggested it was an anti-symptomatic drug. The trials weren’t designed for this

    (b) RXR is a ubiquitous molecule that is found all over the place, as are many of the targets for remyelination agents. Therefore side-effects were always going to be anticipated and these were great. If people can’t tolerate the drugs then they can’t work. People with MS have few nerves and so may be more susceptible the side effects. Also it can be argued that the system was not revuvinated first

    (c) LINGO is a CNS expressed target and antibodies have poor penetration (99.9% excluded) into the CNS. This makes it hard to have a success. Likewise effects of antibodies in Alzheimers Disease are modest.

    However surely it is better to try and fail and learn than not to try at all.

  • Rowing is a great exercise. I think it could be a great add-on since its a fullbody workout and you can either go easy or hard. There’s a lot of emphasis on form so while its repetitive, you are actively ensuring your form stays correct. Well, technically you should focus on your form as bad form can hurt you.

      • Almost every pwms I know, a lot, have balance disorder. When I sit on a rowing machine, or even a chair without a back and side arms, I will be laying on the ground vomitting within seconds.

        Neuroplasticity helped me so much, just by keeping excersizing. Walking backwards was key.

  • Another aspect that is lacking in all our trials is neurorehabilitation, i.e creating the biological stimulus to promote recovery of function

    First time i see you talk abou t this 🙂

    Your stroke colleagues know this very well

    Rehabilitation after a stroke traditionally focuses on patients practicing low-intensity walking, usually only in a forward direction, which does not provide enough of a challenge to the nervous system

    Our study suggests that stroke patients can perform higher intensity walking exercises and more difficult tasks than previously thought possible. We need to move beyond traditional, low-intensity rehabilitation to challenge the nervous and cardiovascular systems so patients can improve function and perform better in the real world.

    “Rehabilitation that allows walking practice without challenging the nervous system doesn’t do enough to make a statistical or clinically significant difference in a patient’s recovery after a stroke,” Hornby said. “We found that when stroke patients are pushed harder, they see greater changes in less time, which translates into more efficient rehabilitation services and improved mobility.

    Watch the movie

    ‘Time is vision’ after a stroke

    The Rochester team found that survivors of occipital strokes—strokes that occur in the occipital lobe of the brain and affect the ability to see—may retain some visual capabilities immediately after the stroke, but these abilities diminish and eventually disappear permanently after approximately six months. By capitalizing on this initial preserved vision, early vision training interventions can help stroke patients recover more of their vision loss than if training is administered after six months.

    Time time and more time

    Nice post

  • Compartmentalized inflammation is probably the main driver of remyelination failure. Targeting EBV within the central nervous system will eliminate the immune response to EBV and therefore the inflammatory process will die down over the next few months and thus will allow for remyelination to take place.

  • I now understand that the capacity of remyelination after relapses depending on the quality of the damage. Would corticosteroids treatments shortly after confirmed relapses help control the damage so better chance of recovery? My first demyelinating attack lasted 6-8 weeks, and I had little recovery assuming the length of the attack made deeper scars.

  • And another one bites the dust:

    From a participant in the Elezanumab trial: “I have received news from other participants in the elezanumab trial, and from my own trial coordinator, that elezanumab will not be continuing to phase 3 clinical trials for multiple sclerosis.”

    One has to ask why there is never ONE success in these remyelination / repair trials. Is there enough work at the proof of concept stage? Does it show that early work involving mice is a waste of time ie the results don’t translate into humans? Easy to be a pessimist when you see an MS trial for remyelination, repair or neuro-protection.

    • Sad news…..but my first thought is when will we learn that using antibodies to treat CNS disease inside the CNS is a problem.
      In a mouse if the antibody penetrates a fraction of a millimeter it covers a large part of the CNS, but it is next to nothing in a human brain. I did not think that this was about remyelination but nerve growth RGMa. Does it say that MS is not a T cell mediated problem
      RGMa modulates T cell responses and is involved in autoimmune encephalomyelitis

      Rieko Muramatsu, Takekazu Kubo, Masahiro Mori, Yuka Nakamura, Yuki Fujita, Tsugio Akutsu, Tatsusada Okuno, Junko Taniguchi, Atsushi Kumanogoh, Mari Yoshida, Hideki Mochizuki, Satoshi Kuwabara & Toshihide Yamashita. RGMa modulates T cell responses and is involved in autoimmune encephalomyelitis. Nature Medicine. 2011; 17:488–494.

By Prof G



Recent Posts

Recent Comments