I have been diagnosed for 12 years now and am 65 years of age.
I have taken a number of DMTs over that time including Tecfidera, Gilenya and Tysabri. Tysabri worked well until I was JCV positive and then I decided to switch to Cladribine. I have now finished my 2 year course of treatment and lymphocyte levels are now back within normal range. Brain MRI's have been stable for a long time since my last relapse back in 2017, which happened after withdrawal from Gilenya therapy. This relapse left me with weakness and numbness in my left leg and some mild mobility problems.
Since then balance, cognition and motor coordination have more recently started to worsen and mild levels of similar symptoms have been noticed in my right leg.
Are these changes a sign of smoldering MS and if so is there anything that might help slow down any disease progression?
Could this increase in symptoms be due to reconstitution of my immune system post treatment?
As I am considered to be doing well by my neurology team they don't seem to be concerned that I am experiencing symptom worsening.
Hi from Florida Dr. G! I too am interested in NVG-291. Also, do you have any feelings about PIPE 307 and IRX 4204? I know it's hard to say much of an authoritative nature at this stage, but in general how do you see the future of remyelination going? We know from experience that not everything will pan out, but should we be hopeful in your view?
Happy new year from London! Could you share latest researches, trials about myeline repair, please? What could be the timeline? A few years away? Decade(s)?
Could AI help in the matter?
I’m a 54 woman, having MS for the past 30 years. Benign until 2020. Dramatically worsened post the pandemic. Ive been moved to DMTs, but handicap increased a lot since the two spinal lesions. Thanks!
Souad, since 2021 Solving MS, a volunteer research group, has maintained a database of MS clinical trials for CURATIVE and/or REGENERATIVE therapies. Of 72 trials, 25 are for remyelination. Also shows the estimated year it could reach FDA approval.
1. Please include your predictions for the norway and australia EBV antiviral trials.
2. What about the new studies questioning EBV as case of MS, like these low percentage found in the brain.
And this new study challenging Bill Robinson's GlialCAM theory?
In-depth analysis of serum antibodies against Epstein-Barr virus lifecycle proteins, and EBNA1, ANO2, GlialCAM and CRYAB peptides in patients with multiple sclerosis. Front Immunol. 2024 Dec 17;15:1487523. doi: 10.3389/fimmu.2024.1487523
3. Is this the healthy scientific process at work? Why does Pro B have an antagonistic view of EBV theories?
I’ve been feeling a heaviness in my foot, like I’m constantly dragging a ball of iron. I’ve been told it’s probably neuropathic pain, and the medication I take for trigeminal neuralgia (Trileptal/Oxcarbazepine) seems to be helping. For a while, it was completely gone, but now I’m feeling it even on a full dose of Trileptal (2x600mg). Is there anything to do? The trigeminal neuralgia is fully helped with this dose (which is the most important).
Clinical trials for new MS treatments often have a lot of exclusion criteria. I’ve been excluded from a few trials because of these. Sometimes, it feels like I’m being excluded because the researchers have an assumption that the treatment won’t work, but I often don’t understand why those aren’t research questions. Do you have any concerns about how relevant the research findings are to patients who usually get care in the NHS or other public healthcare systems, if most aren’t allowed to participate? Why not include everyone who agrees to take part and then do analyses to figure out who the treatment works for later?
Hi Dr. G! Would you please consider discussing concerning aspects in the USA FDA's approval process for MS DMTs? I have extensive information from researching this matter such as detailed notes from different DMT FDA Summary Reviews, etc, but it is too much information to post here. I am happy to email these documents/this information to you. One example: "The general acceptance of the clinical importance of reducing exacerbations was evidenced by the fact that, based on a study in which the only clinical benefit shown was reduction of exacerbations and no effect was demonstrated on lasting disability, an FDA expert advisory committee recommended approval of Betaseron, FDA licensed Betaseron, and many physicians and patients began using it" (from Division of Clinical Trial Design and Analysis: HFM-576; BLA STN 103780/0 Comparative Study of Rebif to Avonex and Orphan Exclusivity). I know that Betaseron is now considered a low-efficacy and outdated MS DMT, but I use this example because it still represents the current view of the FDA, and ARR continues to be the almost exclusive primary endpoint in current MS DMT clinical trials, even though research evidences that almost all MS progression and disability worsening comes from PIRA and not RAW. Thank you!
I am interested in this too. New lesions on MRI (I think this is what you mean by “exacerbation” — others call it “relapse” (the language used around MS baffles me) are the be-all and end-all for many. IS smouldering MS still not acknowledged by many neurologists and scientists?
Hang around; this is one of the bigger topics here, and there is plenty of stuff on it in the Selfie that you can look up. I'm not a med. doctor, but no, "smoldering" is quite neglected and as you are probably aware, most discusions in places like Reddit and Facebook center on the absence of new lesions as being the ultimate answer. However, I have to say that when you are in it (RRMS), the stopping of new attacks is pretty convincing of something good going on.
There are many things to consider. I know you want Prof G's take and I am not a med doctor. I went on Betaseron when it came out near 1994, and did my shots every other day like clock work for 23 years. One report I read mentions it being described as low efficacy [CRAB] because they couldn't get the patients to do the shots regularly. There was no data on long term outcome at the time because (I believe it was put on fast track) no one was going to wait around for 20 years to see how it went, when there was no other treatment and this stuff was reducing lesions by 50 to 80%. This is where the "no new lesions" slogan came from, that I recall. I was headed downhill fast, it seemed, and I steadied out since. Regained a lot of ability through "reserve", which is waning in some areas now, 30 years later. No, there is no cure for MS yet, liked we all hoped Betaseron would be in 1995. You've got to do the best you can. Good luck kb!
Google AI: "Research has shown that statins, a class of drugs used to lower cholesterol, are not effective in treating multiple sclerosis (MS), with a large phase III clinical trial (MS-STAT2) demonstrating that simvastatin did not slow disability progression in people with secondary progressive MS, indicating a failure of statins as a treatment for MS."
This does not consider the effect of statins on cardiovascular and cerebrovascular health, which may be important for pwMS who have risk factors for comorbidities or established comorbidities.
Yes, I take my simvistatin as prescribed. Was hoping there might be some added benefit for me in terms of MS. And I'm not a big proponent of AI; just no time to look up the reference which I thought I had read. But a stroke with MS, how you going to tell what is what, especially in the early MS years? Thanks for your reply.
Having tried all usual treatments for TGN, then palexia & ketamine,
I had successful Cyberknife for TGN over 2 yrs ago, pain has returned, my Radiation Oncologist has ruled out any further cyberknife as could trigger MS relapse. Gabapentin 900mg daily is keeping pain under control for now. Thoughts on pain relief going forward?
Also recently started satevix to help relief Spasticity.. if results arnt satisfactory I am thinking of the Baclofen pump..but terrified of surgery. Your thoughts on this too.
Doctor Gavin I took. I did 3 years of mavenclad cAnd in those first 2 years I got progressively worse. It was only when I got on rituxin that I felt my progression had stopped. I went from standing to bed-bound during mavan. Clad it was a failed med for me!! And not for progressive m s. Your opinion?
I have been diagnosed for 12 years now and am 65 years of age.
I have taken a number of DMTs over that time including Tecfidera, Gilenya and Tysabri. Tysabri worked well until I was JCV positive and then I decided to switch to Cladribine. I have now finished my 2 year course of treatment and lymphocyte levels are now back within normal range. Brain MRI's have been stable for a long time since my last relapse back in 2017, which happened after withdrawal from Gilenya therapy. This relapse left me with weakness and numbness in my left leg and some mild mobility problems.
Since then balance, cognition and motor coordination have more recently started to worsen and mild levels of similar symptoms have been noticed in my right leg.
Are these changes a sign of smoldering MS and if so is there anything that might help slow down any disease progression?
Could this increase in symptoms be due to reconstitution of my immune system post treatment?
As I am considered to be doing well by my neurology team they don't seem to be concerned that I am experiencing symptom worsening.
Thanks,
Judith
Thank you for this million dollar Q. What effectively slows worsening of symptoms in the absence of new lesion activity?
Amazing thanks Prof G
Can you summarise any pivotal studies that are due to deliver results in the next year or so?
Hi from Florida Dr. G! I too am interested in NVG-291. Also, do you have any feelings about PIPE 307 and IRX 4204? I know it's hard to say much of an authoritative nature at this stage, but in general how do you see the future of remyelination going? We know from experience that not everything will pan out, but should we be hopeful in your view?
Best wishes
Dave
Ty, Excellent inquiries. Prof. G. Will surely provide the best info., for sure.
Will these sessions be recorded and available for later viewing at all?
Yes, I am just playing with this feature, but it says it will be available for posting.
I was just gonna ask the same thing.
Me too, because apparently a lot was stirred up!
Happy new year from London! Could you share latest researches, trials about myeline repair, please? What could be the timeline? A few years away? Decade(s)?
Could AI help in the matter?
I’m a 54 woman, having MS for the past 30 years. Benign until 2020. Dramatically worsened post the pandemic. Ive been moved to DMTs, but handicap increased a lot since the two spinal lesions. Thanks!
Souad, since 2021 Solving MS, a volunteer research group, has maintained a database of MS clinical trials for CURATIVE and/or REGENERATIVE therapies. Of 72 trials, 25 are for remyelination. Also shows the estimated year it could reach FDA approval.
https://solvingms.org/research-database
1. Please include your predictions for the norway and australia EBV antiviral trials.
2. What about the new studies questioning EBV as case of MS, like these low percentage found in the brain.
And this new study challenging Bill Robinson's GlialCAM theory?
In-depth analysis of serum antibodies against Epstein-Barr virus lifecycle proteins, and EBNA1, ANO2, GlialCAM and CRYAB peptides in patients with multiple sclerosis. Front Immunol. 2024 Dec 17;15:1487523. doi: 10.3389/fimmu.2024.1487523
3. Is this the healthy scientific process at work? Why does Pro B have an antagonistic view of EBV theories?
I am in the process of writing a journal commentary on this. It is a huge topic and needs its own webinar and MS-Selfie Newsletter,
Hi Dr G, so appreciate your enthusiasm. Could taking DMT’s derail possible future treatments targeting smouldering MS and re-myelination?
I have a clinical and a research question:
I’ve been feeling a heaviness in my foot, like I’m constantly dragging a ball of iron. I’ve been told it’s probably neuropathic pain, and the medication I take for trigeminal neuralgia (Trileptal/Oxcarbazepine) seems to be helping. For a while, it was completely gone, but now I’m feeling it even on a full dose of Trileptal (2x600mg). Is there anything to do? The trigeminal neuralgia is fully helped with this dose (which is the most important).
Clinical trials for new MS treatments often have a lot of exclusion criteria. I’ve been excluded from a few trials because of these. Sometimes, it feels like I’m being excluded because the researchers have an assumption that the treatment won’t work, but I often don’t understand why those aren’t research questions. Do you have any concerns about how relevant the research findings are to patients who usually get care in the NHS or other public healthcare systems, if most aren’t allowed to participate? Why not include everyone who agrees to take part and then do analyses to figure out who the treatment works for later?
What are your thoughts on the potential of NervGen's NVG-291 for MS?
Hi Dr. G! Would you please consider discussing concerning aspects in the USA FDA's approval process for MS DMTs? I have extensive information from researching this matter such as detailed notes from different DMT FDA Summary Reviews, etc, but it is too much information to post here. I am happy to email these documents/this information to you. One example: "The general acceptance of the clinical importance of reducing exacerbations was evidenced by the fact that, based on a study in which the only clinical benefit shown was reduction of exacerbations and no effect was demonstrated on lasting disability, an FDA expert advisory committee recommended approval of Betaseron, FDA licensed Betaseron, and many physicians and patients began using it" (from Division of Clinical Trial Design and Analysis: HFM-576; BLA STN 103780/0 Comparative Study of Rebif to Avonex and Orphan Exclusivity). I know that Betaseron is now considered a low-efficacy and outdated MS DMT, but I use this example because it still represents the current view of the FDA, and ARR continues to be the almost exclusive primary endpoint in current MS DMT clinical trials, even though research evidences that almost all MS progression and disability worsening comes from PIRA and not RAW. Thank you!
I am interested in this too. New lesions on MRI (I think this is what you mean by “exacerbation” — others call it “relapse” (the language used around MS baffles me) are the be-all and end-all for many. IS smouldering MS still not acknowledged by many neurologists and scientists?
Hang around; this is one of the bigger topics here, and there is plenty of stuff on it in the Selfie that you can look up. I'm not a med. doctor, but no, "smoldering" is quite neglected and as you are probably aware, most discusions in places like Reddit and Facebook center on the absence of new lesions as being the ultimate answer. However, I have to say that when you are in it (RRMS), the stopping of new attacks is pretty convincing of something good going on.
There are many things to consider. I know you want Prof G's take and I am not a med doctor. I went on Betaseron when it came out near 1994, and did my shots every other day like clock work for 23 years. One report I read mentions it being described as low efficacy [CRAB] because they couldn't get the patients to do the shots regularly. There was no data on long term outcome at the time because (I believe it was put on fast track) no one was going to wait around for 20 years to see how it went, when there was no other treatment and this stuff was reducing lesions by 50 to 80%. This is where the "no new lesions" slogan came from, that I recall. I was headed downhill fast, it seemed, and I steadied out since. Regained a lot of ability through "reserve", which is waning in some areas now, 30 years later. No, there is no cure for MS yet, liked we all hoped Betaseron would be in 1995. You've got to do the best you can. Good luck kb!
Sounds great.
I'm in!
Look forward to partipating!
Given the recent results of stage 3 research into statins for MS , would you recommend taking them if no other reason to do so?
Google AI: "Research has shown that statins, a class of drugs used to lower cholesterol, are not effective in treating multiple sclerosis (MS), with a large phase III clinical trial (MS-STAT2) demonstrating that simvastatin did not slow disability progression in people with secondary progressive MS, indicating a failure of statins as a treatment for MS."
This does not consider the effect of statins on cardiovascular and cerebrovascular health, which may be important for pwMS who have risk factors for comorbidities or established comorbidities.
Yes, I take my simvistatin as prescribed. Was hoping there might be some added benefit for me in terms of MS. And I'm not a big proponent of AI; just no time to look up the reference which I thought I had read. But a stroke with MS, how you going to tell what is what, especially in the early MS years? Thanks for your reply.
I couldn't make the live session, but looking forward to catching up with the recording when it's available.
https://gavingiovannoni.substack.com/p/ms-selfie-live-q-and-a-1
SPMS, EDSS 6.5, 50yo f, TGN ~8 yrs, MS dx 2005.
Having tried all usual treatments for TGN, then palexia & ketamine,
I had successful Cyberknife for TGN over 2 yrs ago, pain has returned, my Radiation Oncologist has ruled out any further cyberknife as could trigger MS relapse. Gabapentin 900mg daily is keeping pain under control for now. Thoughts on pain relief going forward?
Also recently started satevix to help relief Spasticity.. if results arnt satisfactory I am thinking of the Baclofen pump..but terrified of surgery. Your thoughts on this too.
https://gavingiovannoni.substack.com/p/it-was-the-worst-pain-i-have-ever?utm_source=publication-search
I don't believe mavenclad is for progressive m.S!!
Doctor Gavin I took. I did 3 years of mavenclad cAnd in those first 2 years I got progressively worse. It was only when I got on rituxin that I felt my progression had stopped. I went from standing to bed-bound during mavan. Clad it was a failed med for me!! And not for progressive m s. Your opinion?