Tolebrutinib results offer real hope for people with smouldering MS and possibly how to identify high-risk subjects (PRL+) who are more likely to respond to tolebrutinib
Email question: "PRLs, how are they identified? Is it a special request when doing MRI, or are they seen on routine MRIs? I’m not sure I have heard of them before……."
Paramagnetic rim lesions (PRLs) in multiple sclerosis are detected using susceptibility-weighted imaging (SWI) MRI sequences. These sequences allow visualisation of iron accumulation around specific lesions, appearing as a "rim" of high signal intensity on the image, indicating the presence of a PRL; these lesions are often best seen on high-field strength MRI scanners, such as 3T machines with appropriate imaging protocols. Please be aware that SWI sequences need to be requested and are currently not routine for MS disease monitoring.
Thank you for kindly sharing this reply because I had a similar question. Your response has made me realise that I don’t fully understand what information my neurologist has access to from my baseline and routine monitoring MRIs (NHS). In particular, I don’t understand the limitations of these types of scans. This makes it difficult to know what types of questions I can sensibly ask during consultations.
Great summary (as always!). We had a small side-meeting discussing clinical trial strategies for remyelinating therapies. Being CMO of a company developing just such a therapy, I am obviously more optimistic than you regarding the possibility of having an approved remyelinating therapy to patients within a decade. I would also note that data from the ORATORIO study demonstrated that anti-CD20 was also pretty effective in reducing PRLs vs. placebo. Re EBV: there is no doubt that EBV infection plays a role in disease initiation (at least). It’s really unfortunate that no effort (with the exception of Patrick Küry in Dusseldorf) is being made toward understanding the potential role EBV in activation of HERV-env, a mechanism that could explain a lot of what we see.
The tolebrutinib data is about baseline PRLs predicting response and not about reducing them. There are two kinds of PRLs: those present at baseline and those that develop with time. Ocrelizumab is good at stopping new ones from forming but ineffective at doing much to pre-existing ones. I assume you have seen this paper.
Maggi P, Bulcke CV, Pedrini E, Bugli C, Sellimi A, Wynen M, Stölting A, Mullins WA, Kalaitzidis G, Lolli V, Perrotta G, El Sankari S, Duprez T, Li X, Calabresi PA, van Pesch V, Reich DS, Absinta M. B cell depletion therapy does not resolve chronic active multiple sclerosis lesions. EBioMedicine. 2023 Aug;94:104701. doi: 10.1016/j.ebiom.2023.104701. Epub 2023 Jul 10. PMID: 37437310; PMCID: PMC10436266.
Agreed. Perhaps I misunderstood the data presented? I understood it to show tolebrutinib was effective in preventing CDP (based on EDSS) in participants regardless of their BL PRL burden. Was there data presented on reductions of new / resolution of existing PRLs?
Marrodan M, Yañez P, Calandri IL, Piedrabuena MA, Zárate MA, Ysrraelit MC, Fiol M, Correale J. Impact of oral Cladribine on paramagnetic rim lesions of Multiple Sclerosis patients. Mult Scler Relat Disord. 2025 Feb 22;96:106339. doi: 10.1016/j.msard.2025.106339. Epub ahead of print. PMID: 40020453.
Regrettably, FDA is 60 years behind the times. The issue is: how is a “clinically meaningful” benefit defined? Apparently FDA views the CNS as a “walking machine”, as participants with BL EDSS of 2-5 tend to drive EDSS progression in pivotal MS trials, with worsening in gait as the key functional system score.
Exactly, Dr. Glanzman. I wonder the same thing after reviewing a great deal of the FDA approval documentation for the various MS DMTs in which ARR has been the main primary outcome of the clinical trials that has led to their FDA approvals. The problem with this (in my humble opinion) is that we know from research that relapses and relapse-associated worsening (RAW) barely contribute to disease progression and disability accumulation in MS. In my opinion as well, the classification of MS phenotypes is arbitrary to a good degree. The question then exists of how much of a "clinical benefit" DMTs for relapsing forms of MS have that show good efficacy against the relapse rate and conventional MRI activity (but research shows a weak to moderate association between lesions/lesion activity and progression and disability accumulation in MS (the "clinical-radiological paradox" of MS, RIS, etc) but not against CDP.
I would love to see your trial design. I am not referring to proof-of-biology or proof-of-concept phase 2 trials but phase 3 studies. We cover most of the issues in this commentary:
Ploughman M, Yong VW, Spermon B, Goelz S, Giovannoni G. Remyelination trial failures: Repercussions of ignoring neurorehabilitation and exercise in repair. Mult Scler Relat Disord. 2022 Feb;58:103539. doi: 10.1016/j.msard.2022.103539. Epub 2022 Jan 19. PMID: 35066276.
Why do these international research events always leave me feeling so underwhelmed? With technology advances (imaging, processing power, AI….) you’d think we’d see some real breakthroughs in understanding and treatments. But remyelination / restorative treatments still “decades” away, all quiet on the anti-viral front (are there any MS trials targeting EBV underway?), and the jury is still out on whether BTKis will have much impact on smouldering MS (will liver issues limit their use?). In 2025 the MS research community still seems to be identifying more questions rather than definitively answering existing ones.
Yes exactly that- more questions than answers . Depressing really. Feels like the science is moving at a snail’s pace, while PwMS rocket into the compost bin.
Really appreciate this update ProfG. It’s helpful to have this neat summary as saves wading through lots of info.
I was pleased that remyelination maybe a possibility in years to come - not for myself as a 61 year old, but for the majority struck down by MS when they’re young (I was late onset age 51)
Also delighted to read about Tolebrutinib as treatment for smouldering MS is vital for every single one of us!
I was thinking that MS is one of the few autoimmune diseases treated in monotherapy. Since it is a disease that does not have a single pathway of action (if it exists, it has not yet been proven at last), it would make much more sense to associate mechanisms of action such as anti-VLA-4 with BTKi, or anti-CD20 with S1P or BTKi or a anti-EBV yet to be ready.
There are few studies on this topic and those that exist were done at a time when knowledge was not available today.
Thanks for this excellent overview. As someone with smouldering MS, can you give me a ball park estimate of when tolebrutinib is likely to become available on the NHS? Could it be months away or more likely years? Also, is it selective enough to avoid dampening the immune system significantly, or will it put patients at increased risk of PML, malignancies etc. like other more effective immunomodulators do. Many thanks.
Immunosuppressants slow down the attack on the CNS by immune system , so why can we not use a combination therapy of anti cd20 PLUS remyelinating drugs as treatment. MS progression takes years, so surely a combination therapy of remyelinating drugs plus immunosuppressants is worthwhile as it allows an individual to maintain function. Itll be like a nice workaround until a cure can be found- a constant cycle of damage and repair to keep pwMS functioning with high quality of life. My point is its worth it despite the continued attacks on cns . It buys pwMS some bodily functions back, even though they may be short lived. We would just need to be constantly topped up with remyelinating drugs, just as insulin is used in diabetics.
Not sure that everyone can benefit from remyelination. MS is a demyelinatiing disease, but I am not sure myelin is the primary target. Early in MS, you have enough endogenous repair mechanisms to recover function spontaneously. In advanced MS, if there is too much damage with loss of axons and gliosis, there is no target for repair, or other pathologies (e.g. gliosis of scarring) inhibit repair.
Oh that’s interesting, I didn’t know that. You see, we (PwMS) tend to think think remyelination is the be all and end all. When we first look up ms, first thing you see is that ms is loss of myelin in nerve cells, so we automatically assume, remyelinate nerve cells and we will feel normal again and regain our function. So when does ms become advanced ms/ no target for repair- would SPMS/ smouldering ms tread the line of “no target for repair”? Interesting what you said about maybe myelin is not a primary target. I need to look up gliosis of scarring to better understand your angle here. Your comment is food for thought/ homework for me!
The biggest hurdle for repair is ageing. Unless we can reprogramme cells to become young again, repair is challenging. This is not only an issue with the CNS but also in other organ systems. The best predictor of recovery of function is age, i.e. being young.
I guess this is why the focus is on prevention and tackling ms from the immune angle ( suppressants/ irt). Cant prevent aging, Do we know why the immune system keeps attacking CNS after initial infection of ebv? If aHSCT is given at a young age and at time of diagnosis, would this guarantee ms not progressing or does it only buy you 15 years lets say before it goes into its rrms then spms etc.
In a recent consensus paper under the age of 45, RRMS, active disease, is the best time for HSCT. HSCT is the only potential curative treatment we have at the moment. There are no guarantees, it could give you 10 years of remission, it could give you 20 years of remission. it could give you lifetime remission. Personally I think its worth doing HSCT now for me if you can get at least 5-10 years of remission and potential improvement until something better comes out.
Yes but what if the question is not about relapses/ remission . Smouldering ms (ie spms) is just about constantly feeling crap and constantly losing more bodily functions. Can HSCT stop or reverse that? I get the impression HSCT is only 50:50, works on some , doesn’t work on others. Also sounds like HSCT is better done early at diagnosis before rrms progresses into spms, which is the point of no return? Ie would having HSCT at say 25, stop you from developing SPMS at 40, cause it would halt your MS in its tracks before it matures and does more damage.
As a PwMS who had glandular fever aged 11, I too wonder whether that was the first episode of MS. I recall having no energy to run and feeling exhausted standing in the shower (hot water!). These are both symptoms of my MS experience.
Does Lemtrada/hsct replicate the kidney description, in that it hasn’t got rid of the disease so it will impact the new kidney/immune system in our case again?
Indeed, the real issue is using their treatments early. Trying to remyelinate a damaged nervous system without curing someone of having MS is foolhardy. If the autoimmune target in MS is myelin or the oligodendrocyte, the cell that makes myelin, repairing these two components will invite further attacks on their integrity. It is like doing a kidney transplant in someone with an autoimmune kidney disease. In many autoimmune diseases of the kidney, the disease reoccurs in the transplanted kidney.
RE: "Does Lemtrada/hsct replicate the kidney description, in that it hasn’t got rid of the disease so it will impact the new kidney/immune system in our case again?"
Some patients treated with alemtuzumab and AHSCT, probably a minority, go into very long-term remission with some looking liked they have been cured. Interestingly, many of these patients recover function, i.e. simply switching off the disease allows endogenous repair to occur.
Sadly, in many patients, the remission does not last, and MS disease activity comes back.
Thank you very much for the update and for the review. Would re myelination for inactive secondary Ms make more sense since the disease appears to be dead in a way. In any case, it's the only way, right? The are things happening in the CBI community like nvg291 from Dr. Silver, that gives us some little hope but more people must unite in order to make it real.
To incorporate exercise in a ph3 trial, to trigger remyelinating pathways, one could include a weekly “physio” session in the protocol’s schedule of assessment (online or in person). They could incorporate physio exercises in the form of patient ediaries that need to be completed regularly/ set visits.
Not sure weekly is enough. Proper targeted rehab, such as hand function, must be done several times daily. Each patient will need bespoke rehab to target their unique deficits; a one-size-fits-all physio programme will not be sufficient.
Agree, the only issue is Im not sure how feasible this would be to incorporate in a large ph3 trial. It may be too expensive to implement across all sites globally. It needs to be listed as a primary outcome measure in the protocol to ensure it is done across all patients and monitored well. There has to be a big push and belief from the research community to make this a standard measure in ms trials. Just like safety bloods are a standard measure in all trials.
The study will be negative if they don't incorporate this approach into the clinical trial. Four different remyelination therapies have been abandoned because of poor trial design and not failed biology. When will the MS community learn?
This is disappointing to hear especially as this sounds like a no brainer. Perhaps now that smouldering ms/ PIRA is finally accepted in the ms medical community, next mission is to bang the drum on “activator” methods that must be implemented alongside remyelinating therapies. Your army of soldiers spreading that message i imagine could be physiotherapists/ people specialising in neuroplasticity maybe.
Yes, paramagnetic rim lesions (PRLs) can be detected on a 1.5 Tesla MRI scan, although a higher field 3 Tesla MRI may offer slightly better visualisation.
Thanks for the information. I have no idea what sort of scanner is used in my NHS trust and I have been in multiple different machines over time. Can normal NHS scans identify these lesions? When I have asked my consultant to show me scans and tell me about my lesions I get shown a poor image that he complains about (software issues) and have no real information. He couldn't even show me the new ones that caused him to want to change my medication. Surely it would be helpful to my consultant to have an idea of how many lesions I have, where they are and what type they are?
Email question: "PRLs, how are they identified? Is it a special request when doing MRI, or are they seen on routine MRIs? I’m not sure I have heard of them before……."
Paramagnetic rim lesions (PRLs) in multiple sclerosis are detected using susceptibility-weighted imaging (SWI) MRI sequences. These sequences allow visualisation of iron accumulation around specific lesions, appearing as a "rim" of high signal intensity on the image, indicating the presence of a PRL; these lesions are often best seen on high-field strength MRI scanners, such as 3T machines with appropriate imaging protocols. Please be aware that SWI sequences need to be requested and are currently not routine for MS disease monitoring.
Thank you for kindly sharing this reply because I had a similar question. Your response has made me realise that I don’t fully understand what information my neurologist has access to from my baseline and routine monitoring MRIs (NHS). In particular, I don’t understand the limitations of these types of scans. This makes it difficult to know what types of questions I can sensibly ask during consultations.
Great summary (as always!). We had a small side-meeting discussing clinical trial strategies for remyelinating therapies. Being CMO of a company developing just such a therapy, I am obviously more optimistic than you regarding the possibility of having an approved remyelinating therapy to patients within a decade. I would also note that data from the ORATORIO study demonstrated that anti-CD20 was also pretty effective in reducing PRLs vs. placebo. Re EBV: there is no doubt that EBV infection plays a role in disease initiation (at least). It’s really unfortunate that no effort (with the exception of Patrick Küry in Dusseldorf) is being made toward understanding the potential role EBV in activation of HERV-env, a mechanism that could explain a lot of what we see.
The tolebrutinib data is about baseline PRLs predicting response and not about reducing them. There are two kinds of PRLs: those present at baseline and those that develop with time. Ocrelizumab is good at stopping new ones from forming but ineffective at doing much to pre-existing ones. I assume you have seen this paper.
Maggi P, Bulcke CV, Pedrini E, Bugli C, Sellimi A, Wynen M, Stölting A, Mullins WA, Kalaitzidis G, Lolli V, Perrotta G, El Sankari S, Duprez T, Li X, Calabresi PA, van Pesch V, Reich DS, Absinta M. B cell depletion therapy does not resolve chronic active multiple sclerosis lesions. EBioMedicine. 2023 Aug;94:104701. doi: 10.1016/j.ebiom.2023.104701. Epub 2023 Jul 10. PMID: 37437310; PMCID: PMC10436266.
https://linkinghub.elsevier.com/retrieve/pii/S2352-3964(23)00266-9
Agreed. Perhaps I misunderstood the data presented? I understood it to show tolebrutinib was effective in preventing CDP (based on EDSS) in participants regardless of their BL PRL burden. Was there data presented on reductions of new / resolution of existing PRLs?
I assume you have seen this paper:
Marrodan M, Yañez P, Calandri IL, Piedrabuena MA, Zárate MA, Ysrraelit MC, Fiol M, Correale J. Impact of oral Cladribine on paramagnetic rim lesions of Multiple Sclerosis patients. Mult Scler Relat Disord. 2025 Feb 22;96:106339. doi: 10.1016/j.msard.2025.106339. Epub ahead of print. PMID: 40020453.
https://www.sciencedirect.com/science/article/pii/S2211034825000823?via%3Dihub
It looks like cladribine, which is CNS penetrant, has the edge over anti-CD20 therapies when it comes to targeting smouldering MS and PRLs.
All the presented data was baseline PRL load-predicting treatment response. They did not present data on the treatment effect of tolebrutinib in PRLs.
Regrettably, FDA is 60 years behind the times. The issue is: how is a “clinically meaningful” benefit defined? Apparently FDA views the CNS as a “walking machine”, as participants with BL EDSS of 2-5 tend to drive EDSS progression in pivotal MS trials, with worsening in gait as the key functional system score.
Exactly, Dr. Glanzman. I wonder the same thing after reviewing a great deal of the FDA approval documentation for the various MS DMTs in which ARR has been the main primary outcome of the clinical trials that has led to their FDA approvals. The problem with this (in my humble opinion) is that we know from research that relapses and relapse-associated worsening (RAW) barely contribute to disease progression and disability accumulation in MS. In my opinion as well, the classification of MS phenotypes is arbitrary to a good degree. The question then exists of how much of a "clinical benefit" DMTs for relapsing forms of MS have that show good efficacy against the relapse rate and conventional MRI activity (but research shows a weak to moderate association between lesions/lesion activity and progression and disability accumulation in MS (the "clinical-radiological paradox" of MS, RIS, etc) but not against CDP.
Re: "potential role EBV in activation of HERV-env, a mechanism that could explain a lot of what we see"
I couldn't agree more. This is why we need to test EBV and HERV antivirals in MS.
No argument here. Not sure antivirals are the approach I would take unless it can be shown they reduce HERV-Env.
I would love to see your trial design. I am not referring to proof-of-biology or proof-of-concept phase 2 trials but phase 3 studies. We cover most of the issues in this commentary:
Ploughman M, Yong VW, Spermon B, Goelz S, Giovannoni G. Remyelination trial failures: Repercussions of ignoring neurorehabilitation and exercise in repair. Mult Scler Relat Disord. 2022 Feb;58:103539. doi: 10.1016/j.msard.2022.103539. Epub 2022 Jan 19. PMID: 35066276.
https://linkinghub.elsevier.com/retrieve/pii/S2211-0348(22)00054-2
I also quite agree that exercise will have to be incorporated into any remyelinating Ph2 or Ph3 trial raising the bar to demonstrate efficacy.
That is my favorite paper. Thanks!
(I think the way I've been exercising has helped preserve my mobility, with that paper providing both a mechanism and encouragement to continue.)
Why do these international research events always leave me feeling so underwhelmed? With technology advances (imaging, processing power, AI….) you’d think we’d see some real breakthroughs in understanding and treatments. But remyelination / restorative treatments still “decades” away, all quiet on the anti-viral front (are there any MS trials targeting EBV underway?), and the jury is still out on whether BTKis will have much impact on smouldering MS (will liver issues limit their use?). In 2025 the MS research community still seems to be identifying more questions rather than definitively answering existing ones.
Yes exactly that- more questions than answers . Depressing really. Feels like the science is moving at a snail’s pace, while PwMS rocket into the compost bin.
Really appreciate this update ProfG. It’s helpful to have this neat summary as saves wading through lots of info.
I was pleased that remyelination maybe a possibility in years to come - not for myself as a 61 year old, but for the majority struck down by MS when they’re young (I was late onset age 51)
Also delighted to read about Tolebrutinib as treatment for smouldering MS is vital for every single one of us!
I was thinking that MS is one of the few autoimmune diseases treated in monotherapy. Since it is a disease that does not have a single pathway of action (if it exists, it has not yet been proven at last), it would make much more sense to associate mechanisms of action such as anti-VLA-4 with BTKi, or anti-CD20 with S1P or BTKi or a anti-EBV yet to be ready.
There are few studies on this topic and those that exist were done at a time when knowledge was not available today.
What do you think about this?
I have argued for combination therapy trials for years. It makes complete sense. Let's hope the regulators allow them to happen.
I agree. I have thought why wouldn’t we combine things like BTK + something else? Makes a lot of sense to me
Eg cladribine + btk etc
Thanks for this excellent overview. As someone with smouldering MS, can you give me a ball park estimate of when tolebrutinib is likely to become available on the NHS? Could it be months away or more likely years? Also, is it selective enough to avoid dampening the immune system significantly, or will it put patients at increased risk of PML, malignancies etc. like other more effective immunomodulators do. Many thanks.
I’d also like to know about PML risks on BTKs especially since I’m on tysabri
Do you think Tolebrutinib has also an impact on slowly expanding lesions?
I suspect so, but let's wait for the data. It is being analysed.
Did I miss it completely or is still the HERCULES paper really still not published?
Immunosuppressants slow down the attack on the CNS by immune system , so why can we not use a combination therapy of anti cd20 PLUS remyelinating drugs as treatment. MS progression takes years, so surely a combination therapy of remyelinating drugs plus immunosuppressants is worthwhile as it allows an individual to maintain function. Itll be like a nice workaround until a cure can be found- a constant cycle of damage and repair to keep pwMS functioning with high quality of life. My point is its worth it despite the continued attacks on cns . It buys pwMS some bodily functions back, even though they may be short lived. We would just need to be constantly topped up with remyelinating drugs, just as insulin is used in diabetics.
Not sure that everyone can benefit from remyelination. MS is a demyelinatiing disease, but I am not sure myelin is the primary target. Early in MS, you have enough endogenous repair mechanisms to recover function spontaneously. In advanced MS, if there is too much damage with loss of axons and gliosis, there is no target for repair, or other pathologies (e.g. gliosis of scarring) inhibit repair.
Oh that’s interesting, I didn’t know that. You see, we (PwMS) tend to think think remyelination is the be all and end all. When we first look up ms, first thing you see is that ms is loss of myelin in nerve cells, so we automatically assume, remyelinate nerve cells and we will feel normal again and regain our function. So when does ms become advanced ms/ no target for repair- would SPMS/ smouldering ms tread the line of “no target for repair”? Interesting what you said about maybe myelin is not a primary target. I need to look up gliosis of scarring to better understand your angle here. Your comment is food for thought/ homework for me!
The biggest hurdle for repair is ageing. Unless we can reprogramme cells to become young again, repair is challenging. This is not only an issue with the CNS but also in other organ systems. The best predictor of recovery of function is age, i.e. being young.
I guess this is why the focus is on prevention and tackling ms from the immune angle ( suppressants/ irt). Cant prevent aging, Do we know why the immune system keeps attacking CNS after initial infection of ebv? If aHSCT is given at a young age and at time of diagnosis, would this guarantee ms not progressing or does it only buy you 15 years lets say before it goes into its rrms then spms etc.
In a recent consensus paper under the age of 45, RRMS, active disease, is the best time for HSCT. HSCT is the only potential curative treatment we have at the moment. There are no guarantees, it could give you 10 years of remission, it could give you 20 years of remission. it could give you lifetime remission. Personally I think its worth doing HSCT now for me if you can get at least 5-10 years of remission and potential improvement until something better comes out.
Yes but what if the question is not about relapses/ remission . Smouldering ms (ie spms) is just about constantly feeling crap and constantly losing more bodily functions. Can HSCT stop or reverse that? I get the impression HSCT is only 50:50, works on some , doesn’t work on others. Also sounds like HSCT is better done early at diagnosis before rrms progresses into spms, which is the point of no return? Ie would having HSCT at say 25, stop you from developing SPMS at 40, cause it would halt your MS in its tracks before it matures and does more damage.
This also may be helpful:
https://hms.harvard.edu/news/scientists-identify-new-driver-inflammation-implicated-autoimmune-diseases
As a PwMS who had glandular fever aged 11, I too wonder whether that was the first episode of MS. I recall having no energy to run and feeling exhausted standing in the shower (hot water!). These are both symptoms of my MS experience.
Does Lemtrada/hsct replicate the kidney description, in that it hasn’t got rid of the disease so it will impact the new kidney/immune system in our case again?
Indeed, the real issue is using their treatments early. Trying to remyelinate a damaged nervous system without curing someone of having MS is foolhardy. If the autoimmune target in MS is myelin or the oligodendrocyte, the cell that makes myelin, repairing these two components will invite further attacks on their integrity. It is like doing a kidney transplant in someone with an autoimmune kidney disease. In many autoimmune diseases of the kidney, the disease reoccurs in the transplanted kidney.
RE: "Does Lemtrada/hsct replicate the kidney description, in that it hasn’t got rid of the disease so it will impact the new kidney/immune system in our case again?"
Some patients treated with alemtuzumab and AHSCT, probably a minority, go into very long-term remission with some looking liked they have been cured. Interestingly, many of these patients recover function, i.e. simply switching off the disease allows endogenous repair to occur.
Sadly, in many patients, the remission does not last, and MS disease activity comes back.
Thank you very much for the update and for the review. Would re myelination for inactive secondary Ms make more sense since the disease appears to be dead in a way. In any case, it's the only way, right? The are things happening in the CBI community like nvg291 from Dr. Silver, that gives us some little hope but more people must unite in order to make it real.
The same comments regarding remyelination apply to nvg291. How do we design phase 3 trials?
To incorporate exercise in a ph3 trial, to trigger remyelinating pathways, one could include a weekly “physio” session in the protocol’s schedule of assessment (online or in person). They could incorporate physio exercises in the form of patient ediaries that need to be completed regularly/ set visits.
Not sure weekly is enough. Proper targeted rehab, such as hand function, must be done several times daily. Each patient will need bespoke rehab to target their unique deficits; a one-size-fits-all physio programme will not be sufficient.
what if the problems one has is mostly all sensory? Probably due to a few spinal lesions.
Agree, the only issue is Im not sure how feasible this would be to incorporate in a large ph3 trial. It may be too expensive to implement across all sites globally. It needs to be listed as a primary outcome measure in the protocol to ensure it is done across all patients and monitored well. There has to be a big push and belief from the research community to make this a standard measure in ms trials. Just like safety bloods are a standard measure in all trials.
The study will be negative if they don't incorporate this approach into the clinical trial. Four different remyelination therapies have been abandoned because of poor trial design and not failed biology. When will the MS community learn?
This is disappointing to hear especially as this sounds like a no brainer. Perhaps now that smouldering ms/ PIRA is finally accepted in the ms medical community, next mission is to bang the drum on “activator” methods that must be implemented alongside remyelinating therapies. Your army of soldiers spreading that message i imagine could be physiotherapists/ people specialising in neuroplasticity maybe.
https://gavingiovannoni.substack.com/p/case-study-unrealistic-expectations?utm_source=publication-search
Thank you.
Thanks for the update 😊
Thanks for this summary.
I had been under the impression that you need 3T MRI in order to see PRLs very well. Will 1.5 work for these?
Yes, paramagnetic rim lesions (PRLs) can be detected on a 1.5 Tesla MRI scan, although a higher field 3 Tesla MRI may offer slightly better visualisation.
Thanks for the information. I have no idea what sort of scanner is used in my NHS trust and I have been in multiple different machines over time. Can normal NHS scans identify these lesions? When I have asked my consultant to show me scans and tell me about my lesions I get shown a poor image that he complains about (software issues) and have no real information. He couldn't even show me the new ones that caused him to want to change my medication. Surely it would be helpful to my consultant to have an idea of how many lesions I have, where they are and what type they are?
Also in the spinal cord?