The Future of Multiple Sclerosis Therapy

This is a talk I gave last week in Germany on the Future of MS care. Most of the content I have presented before. I hope you enjoy it.

[@Kat.Finnerty]

I am the black swan. I have reversed symptoms I’ve had for over 10 years. I am cure not only from attacks but I’ve got back what was lost and broken in my body for so long. When I went on a strict diet my neuro told me I was wasting my time, when I went to Israel for stem cell I was told I was wasting my money, when I was in the hospital for steroids instead of lying down I’d do squats and lunges I was told to stop-I should be resting. I’m a rule breaker and gosh have I had to fight back against the establishment for my choices. I’ve had MS since ‘96. It was aggressive and I was told I’d likely be in a wheelchair by the time I was 50. It was also suggested that I should not have children and I should take DMD (at the time was only injections everyday for the rest of my life). I had three kids in three years and it was true I went downhill -but I fought back, and now at fifty I am fitter and stronger than most teens. When I tell dr’s and my neuro they all say keep doing what you’re doing….but they don’t ask the question, what are you doing? The way I cured myself was… Diet, exercise, stem-cell, meditation and spirituality (studying Buddhism), naturopath’s, yoga, tens machines, Low dose naltrexone, Lemtrada…and I’m sure I’m missing so many more. My point is what is lost is not lost forever, there is a cure, there is a way out, but our doctors need to give hope and proper strategies to keep on top off the game…is it hard??? That depends on your perspective, eating chocolate is great, but not being able to walk really sucks. Pushing yourself to exercise even when your ability is limited is frustrating, but slipping further into a hole also really sucks. I believe everyday I have a choice, and that is to do things that will make me stronger or weaker. Mostly I’m motivated and driven, even though I still drink too much champagne and eat chocolate sometimes. Never, ever give up. Thank you for this great work Gavin!!! Hopefully they will now see the black swan

[@maryizard9837]

I agree with everything you say above. I've had MS since 1981, and have been able to reverse some symptoms. I attribute this to a neurological physical therapist, a personal trainer, a holistic healer, and a massage therapist

[@JanetWark]

Positive & Awesome Post!!! #CURE4MS!!!

[@kevindonnelly7475]

Can you explain what you mean by 'stem-cell'? DId you do HSCT or mesenchymal cell transplant? Just curious, I'm newly diagnosed, actually in middle of second opinion, but am eating an anti-inflammatory diet and exercising daily.

[@barbaradascalos4411]

Making huge mistake..get HSCT

[@ernietollar7767]

PPMS or RRMS?

[@alancoss]

Thank you Dr. Giovannoni - from a doctor living with MS. Very reassuring to hear of such promising therapies.

[@Lostnthot]

Thank you Dr. G. I'm a 25+ year ms patient in the U.S. Originally started on the "A, B C's" and moved on to other therapeutics and what you have shared here on this platform is a blessing. This year started cladribine. I have noticed for myself that in the process of starting a physical , MUSIC therapy should be involved in the rehab.

[@opplek]

Thank you very much for this excellent video and the work you're doing. After a family member of mine was diagnosed with MS a couple of years ago, I quickly found your work when researching MS. I was skeptical about EBV being the cause at first, but over the years, the more I read, the more I became convinced you're absolutely right. EBV might not be the *only* cause, because some other things need to fall in place to trigger MS as well, but at this point I have no doubt that EBV needs to be the main target to stop MS. I really hope you can get the iTeri study funded. I really think it would revolutionize MS treatment.

[@isabellaprincess6890]

Thankyou for touching on HIV and MS. When l was diagnosed with MS last year my dad said at least it’s not cancer and my husband said at least it isn’t AIDS. I told my dad some cancers can be cured and when l thought about AIDS and MS l was perplexed. I work in hospitals reviewing medical records and when reflecting realised no patients really had active MS and HIV. I’ve probably read over 200,000 inpatient episodes in my life and realised it was as though the two conditions were mutually exclusive, or the patients with both co-morbidities were never sick enough to require inpatient treatment. I asked my Neuro about it and she didn’t really think there was a correlation. This video answered my question, thanks.

[@SammyJo99]

Look for the case reports on MD patients who caught HIV, started ARV, and MS disappeared.

[@spicyspacecake]

i do love it when i hear people adroitly leveraging Taleb's black swan theory - well done...

[@__Wanderer]

The optimal procedure would be something like this? 1) Immediate action as you describe with HSCT / Cladribine 2) Antivirals + DMT like DMF - seems like a solid approach. Would you also consider promoting other supplements such as B vit/ Omegas/ Alpha lipoic acid or clemastine use? Thank you for your work on this topic - incredibly complex, I hope this can somehow be cured so future generations dont have to suffer from this.

[@thomasdumont1474]

Thank you. Hope is what we need.

[@colleensmith3374]

Dr thank u so much for the great explanation re: the future. It gives us hope

[@naomi5495]

Very astute points and well communicated. Thank you. ❤️ I think you’re very on point with analysis of MS disability progression /causative mechanism. That and aggressive management of other factors in health such as loneliness etc - I think an approach like this would benefit many patients with various chronic diseases. We can but hope that the NHS is healthy enough to achieve this one day.

[@__Wanderer]

Really fantastic talk, thank you professor :)

[@MihaiMezel]

Very interesting! Thank you for these explanations

[@mikejames6408]

Great talk thanks Prof G. So many reasons for hope. I’m taking 80mg simvastatin on top of ocrelizumab, keeping active and looking at fasting/keto. Subscribing to MS-selfie and looking forward to the website launching. Thank you so much

[@barbaradascalos4411]

ocrevus is not helping you... see "onset of secondary progressive ms despite long term Rituximab therapy"

[@pedrodacostapinto]

Hi Dr., I've been following you for quite sometime, I give thanks to doctors like you, fortunately I am in Portugal followed by a great, cutting edge doctor (João Cerqueira,in Braga). I definitely agree with your vision and I'm the leaving proof that neuproplasticity works and is maximised through physical activitie !! Bless you

[@anaribeiro509]

Hiii!!! I am also a pacient of Dr. Joao Cerqueira! Olá. Quanto tempo tens de Diagnóstico e que medicação fazes?

[@pedrodacostapinto]

​​@@anaribeiro509 de momento nada,fiz Alemtuzumab em 2019/2020.sou de Famalicão

[@KinEllKokabel]

Thank you 👍🏻

[@PlatinumRatio]

This is very very exciting. Much love guys. I won't have MS much longer...

[@DrBrandonBeaber]

Excellent presentation prof G.

[@annaburdziej3233]

3 years ago I had mono. Last week I was diagnosed with MS. The connection is very clear. Usually MS appears after 7-8 years after EVB infection. In my case much faster...

[@__Wanderer]

Very interesting to hear your thoughts on MS being built up in layers (that the MRI +Gd +relapse are as a consequence of some underlying mechanism). Essentially we are all trying to get rid of the smoke whilst the fire is still burning somewhere... EBV seems to be a good candidate for that. Antiviral use seems to be a great idea. If in the future if* there ever were to be an "ebv" vaccine - would it have any use for people already living with MS? Perhaps wiping out the immune system with cladribine and giving the vaccine could help in some way / retrain a larger portion of new cells correctly... I am personally on DMF and bought some clemastine** tablets (due to the re-myelination studies) - perhaps this needs to be implemented with DMTs to provide more repair of potential damage.

[@quantumdecoherence1289]

This is what's called thinking outside the box. Maybe you can discuss Atara biotherapeutics anti-EBV T cell therapy. Thanks for all your work.

[@ProfessorGiovannoni]

I have discussed EBV immunotherapy in other MS-Selfie Newsletters in the past. This includes Atara Bio's product.

[@firaskhalifa1675]

Dear Dr. Gavin Giovani, Thank you for your efforts. What are your recommendations regarding MS pregnant on anti-CD 20 medications?

[@mikefraumeni5367]

Excellent presentation and I believe the discussion on the holistic approach to management in MS can reflect the comorbidities and diagnostic uncertainty in cases such as Functional Neurological Disorder eg: "Multiple sclerosis (MS) and functional neurological disorder (FND) are both diagnostically challenging conditions which can present with similar symptoms. We systematically reviewed the literature to identify patients with MS who were misdiagnosed with FND, patients with FND who were misdiagnosed with MS, and reports of patients with both conditions. In addition to FND, we included studies of patients with other functional and psychiatric disorders where these caused symptoms leading to investigation for or a diagnosis of MS, which in a different context would likely have been labeled as FND. Our review suggests that MS is one of the most common causes of misdiagnosis of FND and vice versa. We discuss the clinical errors that appear to result in misdiagnoses, such as over-reliance on psychiatric comorbidity when making a diagnosis of FND or over-reliance on neuroimaging for the diagnosis of MS, and practical ways to avoid them. Comorbidity between these two conditions is also likely common, has been poorly studied, and adds complexity to diagnosis and treatment in patients with both MS and FND. Misdiagnosis and comorbidity in a landscape of emerging evidence-based treatments for both MS and FND are issues not only of clinical importance to the care of these patients, but also to treatment trials, especially of MS, where FND could be a hidden confounder." Source: Walzi D et al. Functional neurological disorder and multiple sclerosis: a systematic review of misdiagnosis and clinical overlap. J Neurol. 2022; 269(2): 654-663 PMID:33611631

[@xaroumenotipota]

In terms of utilising rehabilitation to restore function: what type of rehabilitation could someone with an L2 lesion suffering from neuropathic pain when walking do? I have a type of dysaesthesia similar to Lhermitte’s sign when I walk which has been persisting for over a year now.. Should I try walking more despite the pain, or will that actually make things worse? Thank you in advance for your reply

[@DeanRamser]

Thank you, Dr. Giovannoni, for posting this video. Thank you for your research. We are 66YO. My wife has Secondary Progressive MS. Since visiting Europe (Aug-March this year) from Portland, Oregon, her symptoms have quieted. She has more hours of activity without fatigue and stabbing pain. We wonder if it is the food and walking? Also, we are considering moving to Europe. However, I am not sure if she will receive the same level of care she receives from OHSU. Which country has a strong MS research and treatment center? Thank you. Dean & Cindy

[@asmaabma8822]

I would love so much to have you as my neurologist. Thank you so much for all those informations. I'm a new patient in France, on tecfidera, scared that it's not that effective in a few years. I've heard about a trials on lifnano therapy in Cambridge, i can't find any information about that, i'm wondering if you can say something about it. I hardly find clear and honest informations as those you give, and i'm so not a scientific person so a big big thank you !!

[@TankoxD]

Gavin, Do people with much lower BVL than PwMS in general do better long term or not? You never say this but this is really important.

[@ProfessorGiovannoni]

Low brain volume is a poor prognostic factor and they do worse.

[@scmassa]

Prof G, when you discuss (at around 9 minutes) the patient with quite severe MS who came under Professor Julian Gold’s care for HIV, you mention that his MS “disappeared” and went into “remission” after commencing treatment of anti retro virals. First, what do you mean exactly by those words in inverted commas? The MS went away, disability improved (with exercise / rehabilitation?) or something else? Secondly, how many weeks, months or years did it take for this result, that opened my eyes, ears and inner emotion of hope to occur?

[@ProfessorGiovannoni]

The patients MS went into longterm remission with no relapses and/or MRI activity, and his disability improved.

[@scmassa]

@@ProfessorGiovannoni I am following your views very closely Prof G, particularly your views on aHSCT as a treatment option. I have a question in wth my neurologist (via email) to discuss this when I see her next at the end of February. Let’s see how that goes.

[@1nsanetr]

Great video thank you very much. I noticed something after watching. You did not mention anything about stress. Did I miss it? Or MS is really not related to high stress? Thanks.

[@barbaradascalos4411]

MS is EBV...nothing to do with stress...

[@user-hz1vu1ec5u]

Потрясающе интересно,новый взгляд на проблему рс,лечение!Спасибо большое

[@almondsharrypotter2880]

Hi brilliant talk. One thing I'm confused about is why HSCT is so much more effective for RRMS for stopping progression, than Progressive MS itself

[@ProfessorGiovannoni]

I suggest you read the following: gavingiovannoni.substack.com/p/getting-worse

[@catherinerogers5729]

@@ProfessorGiovannoni This article is great but how do you get your local NHS to listen? I have had constant UTI's since Aug 22 when given steroids for ON (first MS attack) without checking first. MRI & LP show new activity. I really wish they would hit the slow burn quickly ! I'm still waiting for my first DMT - Ponesimod. Can you even do AHSCT with frequent UTI's? I feel powerless right now, the only thing I was/am able to do is switch to a vegan anti flam diet. I wish all neurologists cared the way you seem to.

[@ProfessorGiovannoni]

@@catherinerogers5729 Why do you have so many UTIs? Please read these two MS-Selfie Newsletters to help you self-manage and prevent UTIs. gavingiovannoni.substack.com/p/infection gavingiovannoni.substack.com/p/how-to-interpret-a-urine-dipstick#details You can have AHSCT if you have UTIs; they would put you on prophylactic antibiotics.

[@patriciavanderkooy4113]

What do you think of taking an antiviral ongoing, post HSCT or alongside DMT.

[@niclascage]

Hoping for an answer here. I know you cannot give precise medical advice in this comment section, but I hope you can give a quick, more general answer. My fiancé was diagnosed with RRMS last January. She was diagnosed quickly, about 10 days after onset of symptoms (tingling sensations in her feet and hands). Two weeks later she got her first infusion with either Rituxan or Ocrevus (blind study). She got her second infusion in August, and is due for her third infusion in less than a month. Her MRI was good back in August, no new lesions since she got the diagnosis. My question is - if we have the means to pay for aHSCT, should we do it? Her neurologist (who is one of the top MS doctors in our country) has told us that with early high efficacy treatment she will most likely be fine and can live her life "pretty much like before" until she dies of old age. I fear he is wrong, and that the smouldering (real?) MS will still make her worse as time goes by. We will not be able to get aHSCT in our country, but we have the money to get her the treatment in Moscow or Mexico. I'm just not sure what to do. She is open to whatever I decide, but I don't know. Would you recommend your general newly RRMS diagnosed patient in her mid 30s to get aHSCT if possible? Or would you tell her to stay on her DMT if her MRI is stable? Thanks!

[@ProfessorGiovannoni]

I can't give specific advice, and how you treat individuals depends on many factors. But in general, you are right some people on antiCD20 therapy have smouldering MS and get worse despite being NEIDA.

[@niclascage]

@@ProfessorGiovannoni Thank you. A follow-up question about smouldering MS. Is this something that you think can happen to anyone that have MS, or do you think the load of already existing lesions matter? I read that smouldering MS is driven by SEL, if so I would think that someone with just a few small lesions would have a much better prognosis than someone with a higher number of lesions?

[@dragonfire3727]

​​@@niclascagems is way variables there is nothing in this disease that happened to everyone including smoldering ms

[@demoskunk]

Everyone has smoldering MS. It's the main driver of disability progression.

[@lauriehytner3012]

I am 66 yrs old and I have literally been dismissed as some one worthy of treatment All the DMT's I have taken DID NOT HELP. Where do I go from here?

[@ProfessorGiovannoni]

Difficult to advise without more information. But on the NHS, we never discharge patients as they need regular review and monitoring. If their MS is active they should be offered treatment.

[@lynneheal-xc2qg]

ALL MS MEDS ARE POISONS

[@jacobosantamartabarral434]

Thank you. Why are black Swan events so hard to believe and to understand?

[@ProfessorGiovannoni]

It is one of the cognitive biases of the human brain.

[@jacobosantamartabarral434]

@@ProfessorGiovannoni But I mean we are talking about the brain which is the most complex organ of the human body, how can anyone (no matter how expert) be sure that what the patient says is wrong (even when he or she goes against what seems obvious)

[@fazern4870]

Много интересных тем дядя поднял.

[@alisonbamford6723]

It seems that acute occult B12 deficiency can masquerade as MS & is all too often overlooked. B12 deficiency is often missed & dismissed because many doctors rely solely on serum blood tests which can be very misleading. Not only do they not show cellular levels, neither do they determine what degree of active or inactive B12 is present. If most is inactive it’s not getting into the cells & the test results are meaningless. This can explain why many people with ‘normal’ or even high B12 levels can still display clinical symptoms (although many doctors are not actually aware of those). My own husband collapsed with with what I recognise as abject B12 deficiency symptoms but it was dismissed by the doctor because he considered his B12 level to be perfectly ‘adequate’ (350). However Hub opted to try my sunlingual Active B12 drops rather than go to the hospital (during the CV climate) for more tests. Within 2 days of triple dosing he was starting to rally & within a further week he was back to normal, even though there had been continued regression for well over a week prior to the B12 supplementation. The doctor just said, “well if it’s working, carry on”. 🙄. Had Hub been given loading doses he probably would have improved far quicker. How many people are struggling like he was, barely able to stand unaided, dizzy, weak, awful brain fog, no appetite, etc, because of this very poorly understood, & quite frankly ignored yet so easily treated deficiency status….? Dr. Joseph Chandy (wrote the book ‘B12 deficiency in Clinical Practice’) had diagnosed MS patients who radically improved on B12 therapy. A BMJ article on B12 recently published on the 20th November 23 has a very comprehensive overview of the deficiency & highlights that there is no ‘gold standard’ test for it, so observation & knowledge of clinical symptoms is crucial in the diagnosis. P.S. Thiamine deficiency - Thiamine, like B12 & the other B vitamins either directly or indirectly, is also a crucial player in Nervous System support & repair - can also run concurrently. For various reasons B vitamins can be notoriously hard to acquire or utilise. Our modern refined & processed food places high demands on these crucial vitamins within the body. Many people struggle with digestive issues & that alone can inhibit absorption or utilisation, let alone the drugs they are given, like PPI’s, antacids, Metformin, etc, etc.

[@ProfessorGiovannoni]

Since the nitrous oxide abuse epidemic we now routinely use functional tests for vB12 deficiency. Outside of nitrous oxide abuse acute vB12 deficiency is very rare. It typically develops over months to years and presents as anaemia and/or subacute combined degeneration of the spinal cord.

[@alisonbamford6723]

@@ProfessorGiovannoni I would concur in some ways, but I do think subclinical B12 deficiency is a much bigger issue than is realised, in general. I reversed my so-called ‘diabetic’ neuropathy 15 years ago with diet & supplements, especially the B vitamins. If my B12 is low my first symptom is paresthesia in my hands. Even lower & I develop burning feet & mouth. Lower still & my autonomic breathing is affected. I get ‘air hunger’ & have to consciously breathe. Until I realised it was B12 deficiency it was frightening. Symptoms of course, can differ between individuals, but paresthesia & neuropathies are very common. A lot of issues can develop before the acute spinal cord damage. A new BMJ article published on 20th November pointed out that there is no ‘gold standard’ test for B12 deficiency, & that clinical symptoms observation is a crucial part of observation. Therefore, it is extremely important for doctors to be fully cognisant of the many symptoms. But many, sadly, are not. And not only that, many ‘ranges’ are set way too low, assuming that as long as it is above the bottom of the range it is ‘adequate’. But ‘adequate’ is not optimum, & some people’s bodily demand for it may be far higher. Thank you for your work, however.

[@__Wanderer]

Thank you professor Gavin. I had my first attack after Covid, I think perhaps EBV was also reactivated as I had a terribly sore throat at the time (2 infections at the same time perhaps?) - 4 weeks later severe ON - never had any symptoms prior to that in my life (close to 30 now and am male). Blood tests showed low white blood cell counts + low vit d --> C19 perhaps trashed my immune system and EBV seems to have a knack for inhibiting vit D receptors. I will never know I guess.. My neurologist in the Netherlands didn't allow me to take Ocrevus. I wanted to take something that works because I am terrified of another attack (already blind in one eye after my first relapse). However he advised against it... Mad. He also had terrible bad bedside manners and described how someone died on Ocrevus trying to dissuade me from future use.. insane dutch policy. I am now on * tecfidera / vumerity. Is there a drug which is considered more effective for long term remission? I was considering taking mavenclad perhaps as that seems to pack a punch (in the case I have a breakthrough)

[@ProfessorGiovannoni]

I think you should use this web app to help you decide. The decision on what DMT to start should be yours and not the HCPs. clinicspeak.com/dmt/

[@__Wanderer]

@@ProfessorGiovannoni thanks, chose DMF - as I said above they don't allow Ocrevus as first treatment... they still go by the oldschool protocols sadly.

[@__Wanderer]

@@ProfessorGiovannoni great selection tool btw!

[@pattischmitz2680]

If 95 percent of the population has ebv .. how can this have anything to do with ebv? Thank you!!

[@__Wanderer]

@@pattischmitz2680 Because in the population with MS it is almost a prerequisite (close to 100%). Statistically significant that EBV is almost a "must have" when considering MS. At the very least it seems to be part of the "chain of dominos" relating to MS development. EBN is also nasty in the sense that it hides in our CNS. There is a theory there is some form of molecular mimicry that occurs triggering long term autoimmune problems.