I don’t know about a cure but we haven’t even IEd the antigen in MS. Biomarkers exist, but there’s not one single blood/csf test to nail the diagnosis. As for EBV,
While EBV infection likely contributes to MS risk, the hypothesis that EBV is the singular or primary cause of MS is oversimplified. A more plausible model is that EBV acts as one of many necessary co-factors in genetically susceptible individuals—part of a multifactorial disease process. The causality remains unproven. No EBV directed Rx works.
Axonal loss occurs early. We can talk about oligodendrocytes and microglia and other resident CNS cells but axonal loss is permanent and that is why young patients who end up being in a wheelchair or are completely disabled unfortunately cannot be told that there is a cure around the corner. We have barely scratched or even addressed the neurodegenerative component of MS.
It is incredible how many people misunderstand the statement "necessary but insufficient", even at the Nobel Symposium. If EBV is necessary then preventing people getting EBV will prevent them developing MS regardless of other factors. It is that simple.
In theory, yes. The same Burketts lymphoma. Possibly.
But large clinical science, perhaps needed.
Strong Link with EBV: Burkitt's lymphoma, particularly the endemic type prevalent in certain areas of Africa, has a very strong association with the Epstein-Barr virus (EBV). In fact, nearly all cases of endemic Burkitt lymphoma are associated with EBV infection. It almost sounds like MS and EBV association.
100% agreed. Research shows that the inflammatory and neurodegenerative pathologies and activities that occur simultaneously in MS are at least partially separate and independent from one another as well. There is some research that argues that MS is a primary neurodegenerative disease and not a primary autoimmune disease-that the autoimmune component would be secondary to the primary neurodegeneration. It is odd to me as well that a target antigen (or antigens) has still not been identified in MS.
“He implied that the MS community is satisfied that the efficacy of anti-CD20 therapy is sufficient to manage MS.”
What world do these people live in? Channel 4 News last week had a piece on the Octopus trial with a 38 year old PPMSer confined to his flat. The MS Society website includes a story of a 23 year old woman with advanced MS who lives in a care home.
MS academia seem to be in denial about the real disease (neurodegenerative disease) and the failure of current therapies to have any meaningful impact on it.
I wonder if the family and friends of former footballer Tom Youngs are satisfied with the efficacy of anti-CD20 therapy?
You die of MS. The cause of death is probably infection, but MS makes you too weak to fight it. I think the father of Tom Kerridge died of MS about a decade after diagnosis. The speed of the neuro degeneration is the driver. Those who have MS for 40 years probably have a slower rate of neuro degeneration or better repair.
He died in a hospice which makes infection unlikely as in someone so young they would be aggressively managing something acute. I wonder if he actually had an alternative diagnosis .
I am in the US and a friend who works for hospice took some time off, and was horrified to find upon her return that her hospice patient had not been receiving their pain meds for nearly a week and was going through withdrawals! Hospice is guilty of neglect to the point of abuse sometimes. Being young and on hospice gives no guarantees of better care either.
People w MS commonly die of UTIs. For us, UTIs aren't necessarily"acute" because having neurogenic bladders predisposes us to UTIs, and we often have complicated UTI histories as a result, regardless of age. As someone diagnosed in 20s and confined to wheelchair in 30s (now 50) and who moderates local MS Self-Help Groups, I feel qualified to challenge your opinion.
Now to Professor G - ignorance is at fault for the Nobel Symposium's incredibly short-sighted opinion that pwMS are content with available options. Seriously, it is very clear that academia is lacking the patient-perspective on this. Please recommend that they reach out to Solving MS, a "patient-led charity created to locate, track and fund scientific and/or medical research and share clinical trial status for all forms of Multiple Sclerosis; and to advocate for people with or affected by Multiple Sclerosis.
We are #SolvingMS strong."
In light of the mass-disabling event that Covid-19 has turned out to be, in the past 5 years, the patient-voice in research has appropriately become quite loud and persistent in the demand for a seat at the table.
I would highly recommend that the Symposium read the room, and acknowledge what many in research are finally acknowledging: the patient voice is vital if research is to be better targeted. In essence, including the patients' voice makes success more likely when choosing what to bring to market for the MS community. This seems like it would be obvious, but then again, academia thought for generations that leaving women completely out of clinical research for generations was a good idea 🤦🤷
MS does kill. Here is an interview with Tom Kerridge. His father died in his 40s some 12 years after diagnosis. My aunt died of MS in her early 50s. The outcome is variable, but we should accept that it does shorten the average life span and can be extremely disabling.
Thank you Ian yes I’m aware. I work in a hospice. Most life threatening complications of MS that don’t generate active treatment (hospital) occur at the end of a general trajectory of decline. This seems not to have been the case in the young man above and I wonder if the paper has picked up on him having MS and allowed a story to form that isn’t the entire reality. Regardless I’m very sorry for his family’s loss its truly awful.
I was told when my mum entered a certain hospice that they did not treat you only manage your pain etc.... That if you got infection that they would not treat it. If she wanted to be treated then she had to go to hospital. I do not know the circumstances around this person's care or wishes, or what that hospice offered, I can only say what my family has personal experience of.
"did he died from or with" - was this a dig at the whole COVID nonsense where previously sane people were trying to reduce the seriousness of the pandemic?
Here's a thing.
It depends how much of the immune system decides to attack myelin. In most cases, it's just a tiny bit. But if even a decent amount of B & T cells start - it can be this quick or quicker. The immune system is so powerful, hence needing such massive sledgehammers like antiCD20 monoclonal antibodies to switch it off temporarily. The immune system is designed to repel an entire planet's worth of Invaders. With minor tweaks it can reduce aggressive, metastatic stage 4 cancers to nothing. So - with a really active immune system bent on "protecting" us from myelin, we don't stand a chance.
demyelination is only one aspect of MS pathology and activity and arguably far from the most important aspect in terms of progression as I understand it. For example, there is a sub-type of MS that doesn't even involve white matter demyelination called myelocortical MS. The most concerning aspect of the MS pathology and activity as I see it is PIRA/the neurodegenerative pathology that research has proven is at least partially separate and independent from white matter demyelination.
I wasn't specific about what was being demyelinated. Just that, as a general point, immune systems are extremely powerful and it takes extreme measures to stop them. And those measures don't even fully work, hence PIRA and neurodegenerative pathology in patients who no longer have new lesions / active lesions and are allegedly "stable".
I want to agree with the following sentence from your comment here: "MS academia seem to be in denial about the real disease (neurodegenerative disease) and the failure of current therapies to have any meaningful impact on it."
You are SPOT ON with this comment, as I see and understand it as well! I think the emphasis continues to be on relapses and conventional MRI/lesion activity because that is what the "DMTs" are able to show efficacy against, so it is of course in the interest of the "medical-pharmaceutical-industrial complex" to focus on these aspects since they can say how effective their "DMTs" are for the relapsing forms of MS, even though they know (example here from Genentech, the maker of Ocrevus: https://www.genentech-medinfo.com/content/dam/gene/genentech-medinfo/pdfs/disease-progression-in-ms.pdf?fbclid=IwY2xjawKl8BRleHRuA2FlbQIxMQABHjHqgmjhiH8FA_qwiU-Hbs4MAuA8anAs8gvvb6-CNrbfpgMNFofwJPmjaufS_aem_X39EBKpjmb6x5i3XyP0yLw) that it isn't relapses and new conventional MRI/lesion activity that is the driver/cause of progression in MS, which is PIRA. However, since no DMTs have been able to show efficacy against progression/PIRA/the neurodegenerative pathology of MS, the medical-pharmaceutical-industrial complex continues to focus on the endpoints of relapses and conventional MRI activity, even though they know these endpoints are not very meaningful, as presumably every patient with MS would want a medication that meaningfully slows or even halts progression, which none of the current "DMTs" do. Your frustration in this comment is also the frustration I feel.
The anti-CD20 "therapies" don't even have evidence of meaningful efficacy against progression in the relapsing forms of MS, sadly. What the evidence shows is that they reduce the relative risk of progression (ONLY as measured by/with EDSS) over very-short term periods (the periods of the clinical trials) vs a placebo or a comparator with very high Numbers Needed to Treat (the most effective medications have a NNT of 1, which means that every patient who takes that medication would receive the treatment effect/benefit)
i had EBV at 17 followed by brucellosis which I think impacted on my RRMS diagnosis. My ms has smouldered ever since and at 77 without any interventional drug treatment it’s becoming a very real problem. Movement, pain, eyes , cognition all affected. No new active lesions but plenty visible on scan of brain and spine.
I carry a kind of desolation daily about the lack of treatment or understanding.
I agree that smouldering MS needs attention. I would also like to see a shift towards prehabilitation where newly diagnosed pwMS are evaluated by physiotherapists and given individualised exercises that target neural pathways specific to locations of MS lesions. When I was first diagnosed I had minimal motor deficits even though I had several lesions in my cervical and thoracic cord as well as >10 in my brain. Now, 11 years later I need an AFO and have troubles with dexterity/strength in my hand/arm. I have been doing targeted exercises for a while now that have had minimal improvement in function but at least seems to be preventing worsening. I wonder if I would have less disability if I started targeted exercises earlier.
It takes far too long to actually get a drug to us to try .I have Ppms just get on with approval and let us try hopeful drugs.No hope for us anyway and I personally am tired of all scientific dithering
Yes, and unfortunately the FDA (USA FDA) approval documentation information shows that the evidence of Ocrevus for PPMS from the ORATORIO trial was not found to be evidence from an adequate and well-controlled trial.
This is why Roche/Genentech was asked to do a second Oratorio-HAND trial. I suggest we wait to see the results of this trial before making too many claims about ocrelizumab's ineffectiveness in PPMS. Science is about reproducing results.
I will address the issue of the second ORATORIO-HAND trial later, but for now, I agree that "Science is about reproducing results," which is why the fact that the USA FDA violated their own statutory regulations and guidance by approving Ocrevus for PPMS based solely on one trial that they document was not an "adequate and well-controlled trial" is so troubling. There have been no other trials that I am aware of where any anti-CD20 MS "therapies" have shown efficacy in PPMS (or non-active SPMS for that matter as well). I know there is at least 1 trial where rituximab, which is very similar to Ocrevus, failed to show efficacy for PPMS, which should be a red flag. Even if the results of the ORATORIO-HAND trial are positive, I believe this trial is only assessing upper limb function, which seems to be a pretty low bar. We can't take possible positive results from the ORATORIO-HAND trial and make sweeping or dramatic claims of efficacy. The FDA approval documentation of Ocrevus for PPMS speaks clearly for itself-it is shameful, unethical, egregious, harmful, and revolting.
"I believe this trial is only assessing upper limb function, which seems to be a pretty low bar"
I know from my experience as a "stable" MS patient (according to my neuro here - I have a 2nd opinion declaring my loss of bowel function a year ago to be a relapse but I digress) - my main worry is loss of upper limb function.
I can use enema equipment. I can catherterise when the time comes. I will be able to use sticks and crutches and wheelchairs.
But cognitive fog and fatigue and loss of upper limb function will cause me to lose my job. I can get a walking stick if I can't walk straight but there's no "thinking stick" if I can't think straight. I can use mobility aids and continence aids but if I can't type I can't work.
So - protecting upper limb function is pretty important.
But with that said - we need to find a way to stop PIRA and halt progression. And then ways to reverse it. And none of that seems to be any closer.
Hello from Canada! I will be attending the 2025 EndMS Summer School in Edmonton, Alberta as a speaker on the Lived Experience panel. This year's theme is “The Life Cycle of Innovations for Multiple Sclerosis: Drugs, Vaccines, and Biomarkers”. In my speak titled 'what if I was diagnosed in 2025 instead of 2003?' where i will outline how the changes to McDonald criteria, diagnostics, and treatments available then vs now would have impacted my care and outcome. Other key topics for the week include EBV, NMOSD, and more. While there have been some key advancements we are not at the goal yet. keep up the great work and advocacy.
Also, another interesting and important piece of info to know is that in the tolebrutinib phase 3 HERCULES trial, 74% of participants had been on DMTs, including the "high efficacy DMTs," yet still progressed to non-relapsing SPMS, unfortunately.
“Does initial high efficacy therapy in multiple sclerosis surpass escalation treatment strategy? A comparison of patients with relapsing-remitting multiple sclerosis in the Czech and Swedish national multiple sclerosis registries” by Tereza Hrnciarova
-”In contrast to the previous comparison between the Swedish and Danish cohorts (Spelman et al, 2021), the primary outcome (CDW) did not show a significant difference in favor of the Swedish cohort (...p-value 0.2764)
-”it is reasonable to ask why such a significant reduction in the risk of relapse did not translate into a change in the long-term outcome of CDW”
”Initial high-efficacy disease-modifying therapy in multiple sclerosis: a nationwide cohort study”
-We found a lower probability of 6-month confirmed EDSS score worsening and lower probability of a first relapse in patients starting a heDMT as first therapy, compared to a matched sample starting meDMT.
-This study provides Class III evidence that for patients with MS, starting heDMT lowers the risk of EDSS worsening and relapses compared to starting heDMT.
“The Effect of Disease Modifying Therapies on Disease Progression in Patients
with Relapsing-Remitting Multiple Sclerosis: A Systematic Review and Meta-Analysis”: Georgios Tsivgoulis
-In subsequent subgroup analyses, neither dichotomization of DMDs as “first” and “second” line RRMS therapies [(RR = 0.72, 95% CI = 0.65–0.80) vs. (RR = 0.72, 95% = 0.57–0.91); p = 0.96] nor the route of administration (injectable or oral) [RR = 0.75 (95% CI = 0.64–0.87) vs. RR = 0.74 (95% CI = 0.66–0.83); p = 0.92] had a differential effect on the risk of disability progression
“The Effect of Disease Modifying Therapies on Disability Progression in
Multiple Sclerosis: A Systematic Overview of Meta-Analyses”: Suzi B Claflin et al
-Overall, the meta-analyses included in this overview offer good evidence that,
in general, DMT improve short-term (≤2–3 years) disability progression
outcomes in adults with relapsing forms of MS compared to placebo.
“Early use of high-efficacy disease‑modifying therapies makes the difference in people with multiple sclerosis: an expert opinion”: Massimo Filippi et al
-Growing evidence is suggesting that disability progression in MS patients is only partially secondary to the occurrence of new focal inflammatory demyelinating lesions and clinical relapses (i.e., relapse-associated worsening), whereas progression independent of relapse activity (PIRA) starts from the biological onset of MS and becomes the principal and most relevant driver of disability accumulation in the progressive forms of MS [21,22,23].
- The neurologists of this Expert Opinion paper agreed that a drug should be defined as HE-DMT if its substantial therapeutic effect can be proven on ≥ 1 outcome of inflammation/demyelination but also on ≥ 1 outcome of disease progression (Table 1).
“Clinical Outcomes of Escalation vs Early Intensive Disease-Modifying Therapy in Patients With Multiple Sclerosis”: Katharine Harding et al
-In this cohort study including 592 people, those who received high-efficacy treatment initially had a smaller increase in Expanded Disability Status Scale score at 5 years vs those who first received moderate-efficacy disease-modifying therapy.
-These findings suggest that real-world escalation approaches may be inadequate to prevent unfavorable long-term outcomes
“The Faces of “To Late”-A Surprisingly Progressive Cohort of “Stable” Relapsing Remitting Multiple Sclerosis Patients”: Alin Ciubotaru et al
-80% of RRMS patients in this study (65% were on high efficacy DMTs) showed some type of PIRA after 12 months
-an elevated level of PIRA was found in our cohort, with high efficacy drugs providing no supplementary protection
“Changes in disability in people with multiple sclerosis: a 10-year prospective study” by David Conradsson et al
-The large proportion of our sample receiving immunomodulatory treatment at baseline needs to be taken into account when interpreting the study results. The increase in EDSS scores in our study was similar to previous 10-year follow-ups, monitoring cohorts, where a low proportion received immunomodulatory treatment. The similarities in disease progression between our cohort and previous cohort studies might indicate that changes in severity of MS, as measured with EDSS, occur regardless of immunomodulatory treatment.
Call me cynical, big pharma are in any field of health to make money, which the anti CD20's do for them currently. They need a drug that will be used in the long term to make the money back on the research and make very large profit from it which takes time. And that market is probably at saturation point. There is no incentive for them to put more money into the MS market, their objective is not to cure MS, to stop it even starting, its to make money from MS.
Anti CD20's have been a game changer and it must be satisfying for neurologists to actually have these game changing drugs, they can make a big difference.
However if Neurologists are satisfied with NEAD as the standard is currently, then they are backing up big pharma. If smoldering disease is not universally accepted, if neurologists don't hear a patient saying they are getting worse, but tell them their MS is stable because the MRI from months ago says there are no obvious new lesions then we will not move forward, the money will dry up.
This is why basic research based on money/grants that is derived from sources that is not big Pharma. This is why observation of patients, of hearing patients and most importantly medics and scientists being curious and open minded, that is how we solve the puzzle of MS. We need more thought on the causes and not just the process of MS. Is there a market for big pharma to look into EBV? Is there joined up thoughts on the number of conditions that may be caused by EBV?
If the money is drying up from big pharma then how do you get it from charities, from foundations, from philanthropists. I know you will be doing this now and will have for years. How has the years of government austerity affected basic research not just in the UK but around the world? How will the US president's threats or actual withholding of huge amounts of research money affect MS research? How do you get adequate money that is not linked to big pharma to do the research?
Why did research look at HPV for cervical cancer? Who financed the research for this? And what was the incentive for healthcare services to approve the use of the vaccine? And why only girls for years? I still don't understand why the really obvious was not considered that this vaccine would reduce anal, penile, oral and throat cancer. Why its wasn't given to all young people, girls, boys, non binary and more at the very start?
I find the thought of a dying interest in developing therapies against smouldering MS very unsettling. My MS does not look impressive from the outside, I have no pareses and look like any other 67-year old. But my cognitive fatigue and dysautonomie are getting worse and at times incapacitating. I wished it would stop.
On EBV: in my teenage years three daughters from three befriended families that lived within 1 kilometre of each other, went to the same schools and shared their spare time together, lateron developed MS. I remember a short illness when I was around 16, I was very tired and had thick yellow plaques on my tonsils. Nobody talked about mononucleosis, my tonsils were removed a few months later. My first MS symptoms date from my early twenties. I do have an EBV titre.
Hello Isabelle. Would you mind telling me what dysautonomia symptoms you have. I have not heard of anybody comment about these symptoms with MS. Thank you. Eve
It's not in the interest of the pharmaceutical companies to try to develop therapies against smouldering MS/PIRA when they can just keep "developing" more "DMTs" that reduce relapses and conventional MRI/lesion activity, as they know very well and easily how to do this versus trying to develop therapies that show efficacy against the neurodegenerative (I.e., non-inflammatory) pathology and activity of MS. In my humble opinion, we do not need any more "DMTs" that reduce relapses and conventional MRI/lesion activity-all of the current DMTs do these things. This is why it never makes sense to me that people switch between these DMTs when PIRA appears to occur, as none of these "DMTs" show much (if any) efficacy against PIRA-rather, all of the DMTs really only show efficacy against reducing 2 manifestations of the inflammatory activity of MS: relapses and conventional MRI/lesion activity.
"It's not in the interest of the pharmaceutical companies to try to develop therapies against smouldering MS/PIRA" - I disagree. If they keep us alive and active for longer then we're around longer - other stuff goes wrong and they make money from treating that as well. Dead bodies don't earn money for pharmaceutical companies.
Thank you for sharing the programme. I have greatly valued this little window into the breadth of ms research. It has inspired me to look into the work of some of the researchers and to explore some of these topics in more detail. I am also looking forward to listening to the recording of your presentation which you have kindly offered to share with us. Please do keep sharing, many pwMS are keen to understand the biology behind the disease process and the science underpinning advances in treatments.
I would like to see the input of someone at the symposium who looks at the moral aspect of the pharmaceutical industry choosing to or choosing not to do research for an intervention based on the potential of the biosimilar competitors AND the potential of a cure that would end the gravy train that MS patients allow. Are there medical philosophers that interject the morality piece? In essence, if there is a potential cure but pharma opts not to pursue it, then isn´t pharma just offloading the cost of MS care on to society in general and the individuals with MS because otherwise it would decrease their profits? Is MS the canary in the mine that lays out the purely profit motive of pharma despite the good intentions of individual researchers?
Giovannoni G, Baker D, Schmierer K. The problem with repurposing: Is there really an alternative to Big Pharma for developing new drugs for multiple sclerosis? Mult Scler Relat Disord. 2015 Jan;4(1):3-5. doi: 10.1016/j.msard.2014.11.005. Epub 2014 Nov 21. PMID: 25787047.
Nope. Most pharma companies are listed companies with shareholders; they will claim they have a fiduciary responsibility to make money for the shareholders, who are predominantly pension funds in the UK. Without profits and juicy dividends, pensioners will be poorer.
My, you are moving in lofty ( and well deserved ) circles. As almost always, I totally agree with you , we have not reached Nirvana for MS yet, by quite some way. Looking forward to reading your speech .
Interestingly, both of my sisters had very bad cases of mononucleosis and neither one of them has multiple sclerosis. I on the other hand, never had Mono and yet I am the one with MS.
The relative risk of getting MS after IM is about 2.25. So not everyone who gets IM gets MS; in fact, the lifetime prevalence of MS in people with a history of IM is ~1 in 100.
I'm sure that I have read, possibly from Prof G on here, that not everyone who has IM develops MS but everyone who develops MS has had IM. I am not aware of having IM but maybe I just didn't have debilitating symptoms as we all respond differently to viral infection. I had chicken pox aged 29 which was not fun. I remember it as I have never felt that unwell before or since, but I don't remember either loads or very few spots. I assume I gave it to my 10 month old baby who, 2 weeks later, was absolutely covered in spots and she gave it to my 3.5 year old who, after another 2 weeks, had about 30 spots altogether. So same virus, most likely from a single source as once I got it we were grounded, but 3 very different presentations.
I'm not sure that I understand the question? We are talking 29 years ago! As far as I know it was the first infection with the virus for all 3 of us. The full story is: I felt really unwell for a few days and thought "If I still feel this bad tomorrow I will have to contact the GP". The next day the spots appeared so instead I called my Mum. "Have I had Chicken Pox?" She said "No, we showed you to every child in the area that had it ( as they did in the 70s) and you refused to catch it.". "Ah, well I have it now!" Then we literally wrote off 6 or 7 weeks between us because there was no overlap between us in terms of spots appearing.
Probably that should read EBV not IM as Prof G said 30% for IM. Or I am remembering it wrongly. Anyhow, I just think it's sad that the research we need is not the research that gets funded because Big Pharma generally has to be onboard. Individual research projects have different aims, such as trying existing drugs for other conditions as treatments. In my view the limiting factor is the availability of the money to fund the research. I regularly get "will you help us fund this specific research" emails / letters from the MS society.
I have switched from Tecfidera to Kesimpta 1 year ago. There is no improvement in my condition, I would say my walking is slower & my balance worse. I am 68 years old & was diagnosed 13 years ago. I am really hopeful for Tolebrutinib
Only the headline results of the Musettes study have been released as part of a press release. We need to see the full data set to have a meaningful discussion.
It looks like a good symposium. I think it would have been important to also include reparative strategies for neuronal and axonal mitochondria in the ongoing management of multiple sclerosis, since it is a chronic condition. A few years ago There was some new discoveries and excitement over GDF11 peptide In the brain, and specifically it's use in repairing neuronal mitochondrial dysfunction. Neuronal and axonal mitochondrial dysfunction in the CNS needs to be addressed before the process of multiple sclerosis can sufficiently be arrested and disability reversed, right? No one is there yet, but the research shows that we're getting closer being able to repair some of the damage In the critical subsystems of the CNS support cells, as well as the neurons, axons, and dendrites. Or am I way off? The symposium looks really interesting, and the information seems pretty exciting For the future.
There is a high chance (>50%) of fenebrutinib being superior to tolebrutinib in treating relapsing SPMS, but the results will be similar in the non-relapsing SPMS population. We will know from the relapsing fenebrutinib versus teriflunomide trials; the billion-dollar question is whether or not fenebrutinib will be superior to teriflunomide on relapse reduction. The problem is that the event rates are so low in these trials that the trials may be underpowered to show a positive result.
Because relapse is the introduction to MS for most people. It is pretty scary and brings up all the life and death stuff (and other) they are not prepared to deal with. An assumption is immediately given or formed that by stopping that, the whole thing will be stopped. There are some who do not progress that severely, and their stories and anecdotes form the basis of the idea that stopping relapses stops MS. That would be a cure, in my book. That's what people want, and they convince themselves that they are doing their best to grasp it. What else can you expect? No one is telling them different, (very loudly). They find the rest out on their own, in the context of something gone wrong. Nothing is going unexpectedly, however. It's a disease that pulls at the strings of being human, more so than many others.
I don’t know about a cure but we haven’t even IEd the antigen in MS. Biomarkers exist, but there’s not one single blood/csf test to nail the diagnosis. As for EBV,
While EBV infection likely contributes to MS risk, the hypothesis that EBV is the singular or primary cause of MS is oversimplified. A more plausible model is that EBV acts as one of many necessary co-factors in genetically susceptible individuals—part of a multifactorial disease process. The causality remains unproven. No EBV directed Rx works.
Axonal loss occurs early. We can talk about oligodendrocytes and microglia and other resident CNS cells but axonal loss is permanent and that is why young patients who end up being in a wheelchair or are completely disabled unfortunately cannot be told that there is a cure around the corner. We have barely scratched or even addressed the neurodegenerative component of MS.
Jay Avasarala
U of KY
It is incredible how many people misunderstand the statement "necessary but insufficient", even at the Nobel Symposium. If EBV is necessary then preventing people getting EBV will prevent them developing MS regardless of other factors. It is that simple.
In theory, yes. The same Burketts lymphoma. Possibly.
But large clinical science, perhaps needed.
Strong Link with EBV: Burkitt's lymphoma, particularly the endemic type prevalent in certain areas of Africa, has a very strong association with the Epstein-Barr virus (EBV). In fact, nearly all cases of endemic Burkitt lymphoma are associated with EBV infection. It almost sounds like MS and EBV association.
100% agreed. Research shows that the inflammatory and neurodegenerative pathologies and activities that occur simultaneously in MS are at least partially separate and independent from one another as well. There is some research that argues that MS is a primary neurodegenerative disease and not a primary autoimmune disease-that the autoimmune component would be secondary to the primary neurodegeneration. It is odd to me as well that a target antigen (or antigens) has still not been identified in MS.
You know how to wind me up!
“He implied that the MS community is satisfied that the efficacy of anti-CD20 therapy is sufficient to manage MS.”
What world do these people live in? Channel 4 News last week had a piece on the Octopus trial with a 38 year old PPMSer confined to his flat. The MS Society website includes a story of a 23 year old woman with advanced MS who lives in a care home.
MS academia seem to be in denial about the real disease (neurodegenerative disease) and the failure of current therapies to have any meaningful impact on it.
I wonder if the family and friends of former footballer Tom Youngs are satisfied with the efficacy of anti-CD20 therapy?
https://www.dailymail.co.uk/sport/football/article-14680035/Former-footballer-dies-45-Tom-Youngs.html
Preach it brother. Have PPMS and truly it does not greatly promote having a positive quality of life outcome.
Omg I hadn’t seen this. Did he die from or with MS? That seems such a short timeframe between death and diagnosis.
You die of MS. The cause of death is probably infection, but MS makes you too weak to fight it. I think the father of Tom Kerridge died of MS about a decade after diagnosis. The speed of the neuro degeneration is the driver. Those who have MS for 40 years probably have a slower rate of neuro degeneration or better repair.
He died in a hospice which makes infection unlikely as in someone so young they would be aggressively managing something acute. I wonder if he actually had an alternative diagnosis .
I am in the US and a friend who works for hospice took some time off, and was horrified to find upon her return that her hospice patient had not been receiving their pain meds for nearly a week and was going through withdrawals! Hospice is guilty of neglect to the point of abuse sometimes. Being young and on hospice gives no guarantees of better care either.
People w MS commonly die of UTIs. For us, UTIs aren't necessarily"acute" because having neurogenic bladders predisposes us to UTIs, and we often have complicated UTI histories as a result, regardless of age. As someone diagnosed in 20s and confined to wheelchair in 30s (now 50) and who moderates local MS Self-Help Groups, I feel qualified to challenge your opinion.
Now to Professor G - ignorance is at fault for the Nobel Symposium's incredibly short-sighted opinion that pwMS are content with available options. Seriously, it is very clear that academia is lacking the patient-perspective on this. Please recommend that they reach out to Solving MS, a "patient-led charity created to locate, track and fund scientific and/or medical research and share clinical trial status for all forms of Multiple Sclerosis; and to advocate for people with or affected by Multiple Sclerosis.
We are #SolvingMS strong."
In light of the mass-disabling event that Covid-19 has turned out to be, in the past 5 years, the patient-voice in research has appropriately become quite loud and persistent in the demand for a seat at the table.
I would highly recommend that the Symposium read the room, and acknowledge what many in research are finally acknowledging: the patient voice is vital if research is to be better targeted. In essence, including the patients' voice makes success more likely when choosing what to bring to market for the MS community. This seems like it would be obvious, but then again, academia thought for generations that leaving women completely out of clinical research for generations was a good idea 🤦🤷
The lack of treatment for pain is sadistic, imo.
MumP,
MS does kill. Here is an interview with Tom Kerridge. His father died in his 40s some 12 years after diagnosis. My aunt died of MS in her early 50s. The outcome is variable, but we should accept that it does shorten the average life span and can be extremely disabling.
https://www.mssociety.org.uk/support-and-community/community-blog/chef-tom-kerridge-present-ms-society-bbc-lifeline-appeal
Thank you Ian yes I’m aware. I work in a hospice. Most life threatening complications of MS that don’t generate active treatment (hospital) occur at the end of a general trajectory of decline. This seems not to have been the case in the young man above and I wonder if the paper has picked up on him having MS and allowed a story to form that isn’t the entire reality. Regardless I’m very sorry for his family’s loss its truly awful.
I was told when my mum entered a certain hospice that they did not treat you only manage your pain etc.... That if you got infection that they would not treat it. If she wanted to be treated then she had to go to hospital. I do not know the circumstances around this person's care or wishes, or what that hospice offered, I can only say what my family has personal experience of.
Thanks Ian. Well put.
"did he died from or with" - was this a dig at the whole COVID nonsense where previously sane people were trying to reduce the seriousness of the pandemic?
Here's a thing.
It depends how much of the immune system decides to attack myelin. In most cases, it's just a tiny bit. But if even a decent amount of B & T cells start - it can be this quick or quicker. The immune system is so powerful, hence needing such massive sledgehammers like antiCD20 monoclonal antibodies to switch it off temporarily. The immune system is designed to repel an entire planet's worth of Invaders. With minor tweaks it can reduce aggressive, metastatic stage 4 cancers to nothing. So - with a really active immune system bent on "protecting" us from myelin, we don't stand a chance.
demyelination is only one aspect of MS pathology and activity and arguably far from the most important aspect in terms of progression as I understand it. For example, there is a sub-type of MS that doesn't even involve white matter demyelination called myelocortical MS. The most concerning aspect of the MS pathology and activity as I see it is PIRA/the neurodegenerative pathology that research has proven is at least partially separate and independent from white matter demyelination.
I wasn't specific about what was being demyelinated. Just that, as a general point, immune systems are extremely powerful and it takes extreme measures to stop them. And those measures don't even fully work, hence PIRA and neurodegenerative pathology in patients who no longer have new lesions / active lesions and are allegedly "stable".
https://neurosciencenews.com/t-cells-brain-microbiome-29182/
I want to agree with the following sentence from your comment here: "MS academia seem to be in denial about the real disease (neurodegenerative disease) and the failure of current therapies to have any meaningful impact on it."
You are SPOT ON with this comment, as I see and understand it as well! I think the emphasis continues to be on relapses and conventional MRI/lesion activity because that is what the "DMTs" are able to show efficacy against, so it is of course in the interest of the "medical-pharmaceutical-industrial complex" to focus on these aspects since they can say how effective their "DMTs" are for the relapsing forms of MS, even though they know (example here from Genentech, the maker of Ocrevus: https://www.genentech-medinfo.com/content/dam/gene/genentech-medinfo/pdfs/disease-progression-in-ms.pdf?fbclid=IwY2xjawKl8BRleHRuA2FlbQIxMQABHjHqgmjhiH8FA_qwiU-Hbs4MAuA8anAs8gvvb6-CNrbfpgMNFofwJPmjaufS_aem_X39EBKpjmb6x5i3XyP0yLw) that it isn't relapses and new conventional MRI/lesion activity that is the driver/cause of progression in MS, which is PIRA. However, since no DMTs have been able to show efficacy against progression/PIRA/the neurodegenerative pathology of MS, the medical-pharmaceutical-industrial complex continues to focus on the endpoints of relapses and conventional MRI activity, even though they know these endpoints are not very meaningful, as presumably every patient with MS would want a medication that meaningfully slows or even halts progression, which none of the current "DMTs" do. Your frustration in this comment is also the frustration I feel.
The anti-CD20 "therapies" don't even have evidence of meaningful efficacy against progression in the relapsing forms of MS, sadly. What the evidence shows is that they reduce the relative risk of progression (ONLY as measured by/with EDSS) over very-short term periods (the periods of the clinical trials) vs a placebo or a comparator with very high Numbers Needed to Treat (the most effective medications have a NNT of 1, which means that every patient who takes that medication would receive the treatment effect/benefit)
i had EBV at 17 followed by brucellosis which I think impacted on my RRMS diagnosis. My ms has smouldered ever since and at 77 without any interventional drug treatment it’s becoming a very real problem. Movement, pain, eyes , cognition all affected. No new active lesions but plenty visible on scan of brain and spine.
I carry a kind of desolation daily about the lack of treatment or understanding.
I agree that smouldering MS needs attention. I would also like to see a shift towards prehabilitation where newly diagnosed pwMS are evaluated by physiotherapists and given individualised exercises that target neural pathways specific to locations of MS lesions. When I was first diagnosed I had minimal motor deficits even though I had several lesions in my cervical and thoracic cord as well as >10 in my brain. Now, 11 years later I need an AFO and have troubles with dexterity/strength in my hand/arm. I have been doing targeted exercises for a while now that have had minimal improvement in function but at least seems to be preventing worsening. I wonder if I would have less disability if I started targeted exercises earlier.
It takes far too long to actually get a drug to us to try .I have Ppms just get on with approval and let us try hopeful drugs.No hope for us anyway and I personally am tired of all scientific dithering
Yes, and unfortunately the FDA (USA FDA) approval documentation information shows that the evidence of Ocrevus for PPMS from the ORATORIO trial was not found to be evidence from an adequate and well-controlled trial.
This is why Roche/Genentech was asked to do a second Oratorio-HAND trial. I suggest we wait to see the results of this trial before making too many claims about ocrelizumab's ineffectiveness in PPMS. Science is about reproducing results.
I will address the issue of the second ORATORIO-HAND trial later, but for now, I agree that "Science is about reproducing results," which is why the fact that the USA FDA violated their own statutory regulations and guidance by approving Ocrevus for PPMS based solely on one trial that they document was not an "adequate and well-controlled trial" is so troubling. There have been no other trials that I am aware of where any anti-CD20 MS "therapies" have shown efficacy in PPMS (or non-active SPMS for that matter as well). I know there is at least 1 trial where rituximab, which is very similar to Ocrevus, failed to show efficacy for PPMS, which should be a red flag. Even if the results of the ORATORIO-HAND trial are positive, I believe this trial is only assessing upper limb function, which seems to be a pretty low bar. We can't take possible positive results from the ORATORIO-HAND trial and make sweeping or dramatic claims of efficacy. The FDA approval documentation of Ocrevus for PPMS speaks clearly for itself-it is shameful, unethical, egregious, harmful, and revolting.
"I believe this trial is only assessing upper limb function, which seems to be a pretty low bar"
I know from my experience as a "stable" MS patient (according to my neuro here - I have a 2nd opinion declaring my loss of bowel function a year ago to be a relapse but I digress) - my main worry is loss of upper limb function.
I can use enema equipment. I can catherterise when the time comes. I will be able to use sticks and crutches and wheelchairs.
But cognitive fog and fatigue and loss of upper limb function will cause me to lose my job. I can get a walking stick if I can't walk straight but there's no "thinking stick" if I can't think straight. I can use mobility aids and continence aids but if I can't type I can't work.
So - protecting upper limb function is pretty important.
But with that said - we need to find a way to stop PIRA and halt progression. And then ways to reverse it. And none of that seems to be any closer.
Hello from Canada! I will be attending the 2025 EndMS Summer School in Edmonton, Alberta as a speaker on the Lived Experience panel. This year's theme is “The Life Cycle of Innovations for Multiple Sclerosis: Drugs, Vaccines, and Biomarkers”. In my speak titled 'what if I was diagnosed in 2025 instead of 2003?' where i will outline how the changes to McDonald criteria, diagnostics, and treatments available then vs now would have impacted my care and outcome. Other key topics for the week include EBV, NMOSD, and more. While there have been some key advancements we are not at the goal yet. keep up the great work and advocacy.
Also, another interesting and important piece of info to know is that in the tolebrutinib phase 3 HERCULES trial, 74% of participants had been on DMTs, including the "high efficacy DMTs," yet still progressed to non-relapsing SPMS, unfortunately.
What we don't know yet is if the "high efficacy" DMTs (again, I do NOT like this term, as there is no standard/set/defined criteria in the USA, at least, as to what constitutes a "high efficacy" DMT; my understanding is that in the UK, the ABN criteria for a "high efficacy DMT" is a "DMT" that reduces relapses by 50% or more; however, keep in mind that research shows that relapses aren't associated with long-term progression or CDW in MS (here is one source for this info: https://www.genentech-medinfo.com/content/dam/gene/genentech-medinfo/pdfs/disease-progression-in-ms.pdf?fbclid=IwY2xjawKl8BRleHRuA2FlbQIxMQABHjHqgmjhiH8FA_qwiU-Hbs4MAuA8anAs8gvvb6-CNrbfpgMNFofwJPmjaufS_aem_X39EBKpjmb6x5i3XyP0yLw).
“Does initial high efficacy therapy in multiple sclerosis surpass escalation treatment strategy? A comparison of patients with relapsing-remitting multiple sclerosis in the Czech and Swedish national multiple sclerosis registries” by Tereza Hrnciarova
-”In contrast to the previous comparison between the Swedish and Danish cohorts (Spelman et al, 2021), the primary outcome (CDW) did not show a significant difference in favor of the Swedish cohort (...p-value 0.2764)
-”it is reasonable to ask why such a significant reduction in the risk of relapse did not translate into a change in the long-term outcome of CDW”
”Initial high-efficacy disease-modifying therapy in multiple sclerosis: a nationwide cohort study”
-We found a lower probability of 6-month confirmed EDSS score worsening and lower probability of a first relapse in patients starting a heDMT as first therapy, compared to a matched sample starting meDMT.
-This study provides Class III evidence that for patients with MS, starting heDMT lowers the risk of EDSS worsening and relapses compared to starting heDMT.
“The Effect of Disease Modifying Therapies on Disease Progression in Patients
with Relapsing-Remitting Multiple Sclerosis: A Systematic Review and Meta-Analysis”: Georgios Tsivgoulis
-In subsequent subgroup analyses, neither dichotomization of DMDs as “first” and “second” line RRMS therapies [(RR = 0.72, 95% CI = 0.65–0.80) vs. (RR = 0.72, 95% = 0.57–0.91); p = 0.96] nor the route of administration (injectable or oral) [RR = 0.75 (95% CI = 0.64–0.87) vs. RR = 0.74 (95% CI = 0.66–0.83); p = 0.92] had a differential effect on the risk of disability progression
“The Effect of Disease Modifying Therapies on Disability Progression in
Multiple Sclerosis: A Systematic Overview of Meta-Analyses”: Suzi B Claflin et al
-Overall, the meta-analyses included in this overview offer good evidence that,
in general, DMT improve short-term (≤2–3 years) disability progression
outcomes in adults with relapsing forms of MS compared to placebo.
“Early use of high-efficacy disease‑modifying therapies makes the difference in people with multiple sclerosis: an expert opinion”: Massimo Filippi et al
-Growing evidence is suggesting that disability progression in MS patients is only partially secondary to the occurrence of new focal inflammatory demyelinating lesions and clinical relapses (i.e., relapse-associated worsening), whereas progression independent of relapse activity (PIRA) starts from the biological onset of MS and becomes the principal and most relevant driver of disability accumulation in the progressive forms of MS [21,22,23].
- The neurologists of this Expert Opinion paper agreed that a drug should be defined as HE-DMT if its substantial therapeutic effect can be proven on ≥ 1 outcome of inflammation/demyelination but also on ≥ 1 outcome of disease progression (Table 1).
“Clinical Outcomes of Escalation vs Early Intensive Disease-Modifying Therapy in Patients With Multiple Sclerosis”: Katharine Harding et al
-In this cohort study including 592 people, those who received high-efficacy treatment initially had a smaller increase in Expanded Disability Status Scale score at 5 years vs those who first received moderate-efficacy disease-modifying therapy.
-These findings suggest that real-world escalation approaches may be inadequate to prevent unfavorable long-term outcomes
“The Faces of “To Late”-A Surprisingly Progressive Cohort of “Stable” Relapsing Remitting Multiple Sclerosis Patients”: Alin Ciubotaru et al
-80% of RRMS patients in this study (65% were on high efficacy DMTs) showed some type of PIRA after 12 months
-an elevated level of PIRA was found in our cohort, with high efficacy drugs providing no supplementary protection
“Changes in disability in people with multiple sclerosis: a 10-year prospective study” by David Conradsson et al
-The large proportion of our sample receiving immunomodulatory treatment at baseline needs to be taken into account when interpreting the study results. The increase in EDSS scores in our study was similar to previous 10-year follow-ups, monitoring cohorts, where a low proportion received immunomodulatory treatment. The similarities in disease progression between our cohort and previous cohort studies might indicate that changes in severity of MS, as measured with EDSS, occur regardless of immunomodulatory treatment.
Call me cynical, big pharma are in any field of health to make money, which the anti CD20's do for them currently. They need a drug that will be used in the long term to make the money back on the research and make very large profit from it which takes time. And that market is probably at saturation point. There is no incentive for them to put more money into the MS market, their objective is not to cure MS, to stop it even starting, its to make money from MS.
Anti CD20's have been a game changer and it must be satisfying for neurologists to actually have these game changing drugs, they can make a big difference.
However if Neurologists are satisfied with NEAD as the standard is currently, then they are backing up big pharma. If smoldering disease is not universally accepted, if neurologists don't hear a patient saying they are getting worse, but tell them their MS is stable because the MRI from months ago says there are no obvious new lesions then we will not move forward, the money will dry up.
This is why basic research based on money/grants that is derived from sources that is not big Pharma. This is why observation of patients, of hearing patients and most importantly medics and scientists being curious and open minded, that is how we solve the puzzle of MS. We need more thought on the causes and not just the process of MS. Is there a market for big pharma to look into EBV? Is there joined up thoughts on the number of conditions that may be caused by EBV?
If the money is drying up from big pharma then how do you get it from charities, from foundations, from philanthropists. I know you will be doing this now and will have for years. How has the years of government austerity affected basic research not just in the UK but around the world? How will the US president's threats or actual withholding of huge amounts of research money affect MS research? How do you get adequate money that is not linked to big pharma to do the research?
Why did research look at HPV for cervical cancer? Who financed the research for this? And what was the incentive for healthcare services to approve the use of the vaccine? And why only girls for years? I still don't understand why the really obvious was not considered that this vaccine would reduce anal, penile, oral and throat cancer. Why its wasn't given to all young people, girls, boys, non binary and more at the very start?
I find the thought of a dying interest in developing therapies against smouldering MS very unsettling. My MS does not look impressive from the outside, I have no pareses and look like any other 67-year old. But my cognitive fatigue and dysautonomie are getting worse and at times incapacitating. I wished it would stop.
On EBV: in my teenage years three daughters from three befriended families that lived within 1 kilometre of each other, went to the same schools and shared their spare time together, lateron developed MS. I remember a short illness when I was around 16, I was very tired and had thick yellow plaques on my tonsils. Nobody talked about mononucleosis, my tonsils were removed a few months later. My first MS symptoms date from my early twenties. I do have an EBV titre.
Thank you for your dedication!
Hello Isabelle. Would you mind telling me what dysautonomia symptoms you have. I have not heard of anybody comment about these symptoms with MS. Thank you. Eve
It's not in the interest of the pharmaceutical companies to try to develop therapies against smouldering MS/PIRA when they can just keep "developing" more "DMTs" that reduce relapses and conventional MRI/lesion activity, as they know very well and easily how to do this versus trying to develop therapies that show efficacy against the neurodegenerative (I.e., non-inflammatory) pathology and activity of MS. In my humble opinion, we do not need any more "DMTs" that reduce relapses and conventional MRI/lesion activity-all of the current DMTs do these things. This is why it never makes sense to me that people switch between these DMTs when PIRA appears to occur, as none of these "DMTs" show much (if any) efficacy against PIRA-rather, all of the DMTs really only show efficacy against reducing 2 manifestations of the inflammatory activity of MS: relapses and conventional MRI/lesion activity.
"It's not in the interest of the pharmaceutical companies to try to develop therapies against smouldering MS/PIRA" - I disagree. If they keep us alive and active for longer then we're around longer - other stuff goes wrong and they make money from treating that as well. Dead bodies don't earn money for pharmaceutical companies.
Thank you for sharing the programme. I have greatly valued this little window into the breadth of ms research. It has inspired me to look into the work of some of the researchers and to explore some of these topics in more detail. I am also looking forward to listening to the recording of your presentation which you have kindly offered to share with us. Please do keep sharing, many pwMS are keen to understand the biology behind the disease process and the science underpinning advances in treatments.
I would like to see the input of someone at the symposium who looks at the moral aspect of the pharmaceutical industry choosing to or choosing not to do research for an intervention based on the potential of the biosimilar competitors AND the potential of a cure that would end the gravy train that MS patients allow. Are there medical philosophers that interject the morality piece? In essence, if there is a potential cure but pharma opts not to pursue it, then isn´t pharma just offloading the cost of MS care on to society in general and the individuals with MS because otherwise it would decrease their profits? Is MS the canary in the mine that lays out the purely profit motive of pharma despite the good intentions of individual researchers?
You may find this article interesting.
Giovannoni G, Baker D, Schmierer K. The problem with repurposing: Is there really an alternative to Big Pharma for developing new drugs for multiple sclerosis? Mult Scler Relat Disord. 2015 Jan;4(1):3-5. doi: 10.1016/j.msard.2014.11.005. Epub 2014 Nov 21. PMID: 25787047.
Nope. Most pharma companies are listed companies with shareholders; they will claim they have a fiduciary responsibility to make money for the shareholders, who are predominantly pension funds in the UK. Without profits and juicy dividends, pensioners will be poorer.
My, you are moving in lofty ( and well deserved ) circles. As almost always, I totally agree with you , we have not reached Nirvana for MS yet, by quite some way. Looking forward to reading your speech .
Interestingly, both of my sisters had very bad cases of mononucleosis and neither one of them has multiple sclerosis. I on the other hand, never had Mono and yet I am the one with MS.
The relative risk of getting MS after IM is about 2.25. So not everyone who gets IM gets MS; in fact, the lifetime prevalence of MS in people with a history of IM is ~1 in 100.
Only about 30% of pwMS have a history of IM.
I'm sure that I have read, possibly from Prof G on here, that not everyone who has IM develops MS but everyone who develops MS has had IM. I am not aware of having IM but maybe I just didn't have debilitating symptoms as we all respond differently to viral infection. I had chicken pox aged 29 which was not fun. I remember it as I have never felt that unwell before or since, but I don't remember either loads or very few spots. I assume I gave it to my 10 month old baby who, 2 weeks later, was absolutely covered in spots and she gave it to my 3.5 year old who, after another 2 weeks, had about 30 spots altogether. So same virus, most likely from a single source as once I got it we were grounded, but 3 very different presentations.
I'm not sure that I understand the question? We are talking 29 years ago! As far as I know it was the first infection with the virus for all 3 of us. The full story is: I felt really unwell for a few days and thought "If I still feel this bad tomorrow I will have to contact the GP". The next day the spots appeared so instead I called my Mum. "Have I had Chicken Pox?" She said "No, we showed you to every child in the area that had it ( as they did in the 70s) and you refused to catch it.". "Ah, well I have it now!" Then we literally wrote off 6 or 7 weeks between us because there was no overlap between us in terms of spots appearing.
Probably that should read EBV not IM as Prof G said 30% for IM. Or I am remembering it wrongly. Anyhow, I just think it's sad that the research we need is not the research that gets funded because Big Pharma generally has to be onboard. Individual research projects have different aims, such as trying existing drugs for other conditions as treatments. In my view the limiting factor is the availability of the money to fund the research. I regularly get "will you help us fund this specific research" emails / letters from the MS society.
Sorry, but gets me wondering, were these all break-through infections with chicken pox?
I have switched from Tecfidera to Kesimpta 1 year ago. There is no improvement in my condition, I would say my walking is slower & my balance worse. I am 68 years old & was diagnosed 13 years ago. I am really hopeful for Tolebrutinib
I am wondering if there will be any discussion about the Ocrevus MUSETTE trial (https://www.neurologylive.com/view/genentech-reports-high-dose-ocrelizumab-failed-show-additional-benefit-relapsing-ms) at this symposium. After reviewing the programme, it appears that there will be lots of celebration about the alleged "miracle" of the b-cell depleting "DMTs" for MS, so it will be interesting to see if the MUSETTE trial will be brought up at all.
Only the headline results of the Musettes study have been released as part of a press release. We need to see the full data set to have a meaningful discussion.
I hope the full data set will be made available, but I have my doubts about this, unfortunately.
It looks like a good symposium. I think it would have been important to also include reparative strategies for neuronal and axonal mitochondria in the ongoing management of multiple sclerosis, since it is a chronic condition. A few years ago There was some new discoveries and excitement over GDF11 peptide In the brain, and specifically it's use in repairing neuronal mitochondrial dysfunction. Neuronal and axonal mitochondrial dysfunction in the CNS needs to be addressed before the process of multiple sclerosis can sufficiently be arrested and disability reversed, right? No one is there yet, but the research shows that we're getting closer being able to repair some of the damage In the critical subsystems of the CNS support cells, as well as the neurons, axons, and dendrites. Or am I way off? The symposium looks really interesting, and the information seems pretty exciting For the future.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8109099/#sec10
What chance do you give fenebrut. in being superior to tolebrut. In SPMS?
There is a high chance (>50%) of fenebrutinib being superior to tolebrutinib in treating relapsing SPMS, but the results will be similar in the non-relapsing SPMS population. We will know from the relapsing fenebrutinib versus teriflunomide trials; the billion-dollar question is whether or not fenebrutinib will be superior to teriflunomide on relapse reduction. The problem is that the event rates are so low in these trials that the trials may be underpowered to show a positive result.
But research shows that relapses aren't associated with long-term progression or CDW in MS (here is one source: https://www.genentech-medinfo.com/content/dam/gene/genentech-medinfo/pdfs/disease-progression-in-ms.pdf?fbclid=IwY2xjawKl8BRleHRuA2FlbQIxMQABHjHqgmjhiH8FA_qwiU-Hbs4MAuA8anAs8gvvb6-CNrbfpgMNFofwJPmjaufS_aem_X39EBKpjmb6x5i3XyP0yLw), so why does there continue to be such an emphasis on reducing relapses/ARR as an endpoint in clinical trials for MS "DMTs"? I would argue that it is because it is the lowest bar to meet in terms of an endpoint in MS "DMT" clinical trials, but that doesn't make it meaningful.
Because relapse is the introduction to MS for most people. It is pretty scary and brings up all the life and death stuff (and other) they are not prepared to deal with. An assumption is immediately given or formed that by stopping that, the whole thing will be stopped. There are some who do not progress that severely, and their stories and anecdotes form the basis of the idea that stopping relapses stops MS. That would be a cure, in my book. That's what people want, and they convince themselves that they are doing their best to grasp it. What else can you expect? No one is telling them different, (very loudly). They find the rest out on their own, in the context of something gone wrong. Nothing is going unexpectedly, however. It's a disease that pulls at the strings of being human, more so than many others.