Do you think we have gone backwards with regard to our understanding of MS and how to effectively treat it? I was diagnosed when Natalizumab was approved and there was so much hope with regard to stopping MS and a future of remyelination, and even neuro-restoration. Roll forward 18 years and the very best anti-inflammatories don’t seem to stop MS – rather the neurodegeneration / smouldering MS seems to do its damage in the background. We seem no nearer to identifying the trigger and / or driver of MS. MSers want one thing – not to lose function / not to become disabled, but progressive MS (apart from those with focal inflammation) have no treatments. The wheels of the remyelination wagon appear to have fallen off – all hopes seem to be pinned on the Cambridge trial which doesn’t even start until March 2022. Am I right to feel so pessimistic or might we hear about some breakthroughs in 2022?
There seems to be a continuous flow of evidence that MS is caused by EBV over the last 18 years, but few neurologists seem to be paying any attention. I suspect a generation of neurologists have been indoctrinated by the un-evidenced belief that MS is a random autoimmune event. I think some of the cognitively impaired neurologists will need to retire or die before treatment can truly make progress. Meanwhile, our disease will continue to smoulder and we’ll be damaged by the dogma/EBV.
Do you think exercise or specific types such as resistance training, HIIT or steady sate cardio for example will ever be deemed a DMT for the long term treatment strategy for MS?
Probably not….my take on this would be if it does not carry a side effect risk, then it is not a potent enough effect….you can’t have it both ways so the microbiome change, vitamin D, diet x and y all fall into this problem. If proved wrong I will hold up my hands and say I was wrong but for the past forty years I have been listening to this and that quack science from quacks and academic quacks and nothing has come of it, millions have been flushed down the toilet, piles of science papers have been written and what have you got to show for it….I lot of lost hope.
Do I think exercise is beneficial absolutely…but its not a DMT
I know what your saying about the side effects, however I do believe a lot of factors that don’t have side effects can add up to a huge difference. For example ‘not smoking’ doesn’t have any side effects or neither does ‘smoking’ really, at least short or medium term however it can have a huge effect on progression.
There are no neuroprotective drugs in MS unless ‘anti-inflammatory’ drugs count as neuroprotective. Progression is an issue in MS independent of relapses as we know.
It would be interesting to see rates of brain atrophy, boost to mitochondria, increased energy production etc, even remylination and the holy grail of reduced EDSS with prolonged exercise.
I do believe you have to join all of these factors together, however small the benefits. Exercise could be a one of the best neuroprotectants and improver in quality of life we have but generally not promoted
I walked home from work yesterday, at a very fast pace. Took 50 minutes and I felt amazing when I got home. Refreshed and revitalised. Exercise is great.
Hello and happy new year. I’m hoping to persuade my neuro to prescribe cladribine off-label. I understand the Barts protocol is in the public domain – thanks ProfK – is there a web page where this can be seen?
I am keen to look into getting cladribine off-label, and Prof K kindly indicated the Barts protocol is in the public domain. Is there a website where one can access this?
Have been kindly provided with a pcr test kit for if/when I get covid.
I have low lymphocytes due to cladribine treatment – my guess they are currently 0.6
It is suggested I get anti viral medication if I get the virus and ideally as soon as possible after positive test.
Do you agree? Or should I keep fingers crossed and fight it
I am fairly healthy and had ‘fourth booster’ just after Xmas and bmi is 27 ish
What do they call someone who does the same thing over and over again, yet expects a different outcome?
P.S. Like the new format and happy to see MD1 got his quick wit back. My favorite disclaimer to date…..“ I am not giving advice…read the papers and make up your own mind” 😂
How can I determine BVL in vivo; don’t want to give my whole brain to science yet? I’m not on any DMTs or another meds, and have to fight even for a triennial MRI down here? Don’t have clue what antibody response I may mount re: covid. I often feel totally forgotten (though you and Prof G have kindly acknowledged my swimming activities in posts over the year). As to clinic, one annual call is probably all I can expect.
BVL is one data point that AI-supported MRI reading provides. At the moment, there is no consequence emerging from BVL alone, which is why it is currently not available as part of routine follow-up (except for eyeballing/comment by the clinician).
In regards to the PCR test and access to anti- virals ( which didn’t even know about until I read on here ) is this only for people on the monoclonal antibodies or severely disabled or would all people with ms On dmt’s or be entitled.
Thanks
Remember ronapreve does not work against omicron.
Access to antivirals should be for anyone with risks of a bad time this could be age, co-morbidity and immunosupression/modulation should fit into that category
Interesting many years ago I worked in a place with an animal scanner as soon as the magnet went on metal objects would fly….a workmans hammer was the memorable one straight down the barrel and £10,000 worth of damage:-)
I would probably be claustrophobic in that. If the technology could progress and be similar to a space helmet but leave the lower face uncovered – mouth and nose, that would be amazing and the ideal. A few more years to go for that…….
I know that cladribine is lauded on this blog but what are the advantage of a shift from ocrelizumab to cladribine? BBB penetrant? t-cell depleter? i know that the main impact is on b-cells and this has proven not to be too effective with ocrelizumab, hence the switch. It seems that the lack of MRI activity, despite relapses (as per the definition) means that HSCT and alemtuzumab are still off the table
Advantages….convenient, safety, efficacy, CNS penetrance, COVID friendlier, etc…the question is the reason for failure. Each agent has pluses and negatives so make sure you do your homeowrok so you are satisfied with your choice
Thank you MD. I have done a lot of homework but unfortunately there are too many unanswered questions. Even the heavily trained neuros cant decide the best approach so what chance a patient. Ultimately, my decision is based on currently feeling like crap each day and increasing symptoms, which drives up my willingness to risk. I have accepted that i will never undertstand the science so its a bit of a leap of faith…..can anyone really answer the question of why ocrelizumab has failed? is my diseases t-cell driven? i have OCB, which suggests b-cell involvement. I have considered cladribine for its penetrability (is that a word?) but would be concerned that it is considered to have less efficacy that ocrelizumab and is less potent as a b-cell depleter. If the problem is already established in my CNS then alemtuzumab aint going to help with that. HSCT might but at the cost of 5-10 years reserve on top of £40k and the significant threat of covid. Sorry, turned in to a rant and not at you obviously but you can appreciate the dilemma
Microclots are becoming a hot topic in long covid. There are no established tests to check it though and there are only some experimental treatments (like apheresis). I wonder if microclots can be found in MS patients too, and if this is why CCSVI was bringing some symptomatic relief in MS patients like on brain fog (even if it didnt control the disease).
Easy stress ,stress and post traumatic stress disorder (PTSD)
extreme trauma causes the increased myelination,
At the time, scientists looking for changes in myelination related to brain disorders were focused on the cortex’s white matter, which is mostly myelinated. In multiple sclerosis, for example, an autoimmune attack destroys myelin in the white matter. Kaufer was perhaps the first to find evidence of increased myelination in the gray matter associated with disease.
Chao and Neylan did find increased myelination of neurons in the gray matter of veterans with PTSD, but not in those without PTSD. The worse the symptoms, the greater the myelination
Doing a bit of research into HSCT and came across this post /comment:
“There are two approaches one is non ablative meaning that you can keep your immune system and here the HSCT allow you to use a bigger dose.of DMT.
The other is ablative meaning that you have a clear out of your immune system and so you need vaccinations again.
Therefore how much drug do they give CY will clear out.dividing cells but not those no dividing and the rituximab will hit B cells. So what gets rid of the t cells.
Whilst cyclophosphamide can get in the brain, rituximab wont and so
immune system in brain is not going to get touched so HSVT does not get rid of oligoclonal bands, so probably less effective in spms ppms”
Is the suggestion here that patients with OCB will not benefit from HSCT in terms of preventing their transition from RRMS to SPMS? does the non-mylo regimen not include drugs to get rid of the t-cells? if not, what is the cyclophosphamide do? why not just give rituximab. Very confusing for a patient to understand when is too far gone
After many years of finding blood tests painful, today I found out about Emla cream to numb the skin first, (lidocaine & prilocaine), available over the counter.
How do we square the fact that Ebv as time to infect memory b cells of a 2 years old child an allmost
imediately develop ms
Also a 2 year old does nt seem to have manny memory b cells yet
We also observed a gradual slight increase in the percentage of CD27+ IgD+ B-cells, whereas the percentage
of
CD27+ IgD- B-cells increased more rapidly between the 6–18 months and 18 months to 4 years age groups, reaching a peak at the age of 8–12 years before stabilizing
B-cell subpopulations in children: National reference values
More interest in targeting EBV Tevogen Bio is now also interested in targeting ebv for multiple sclerosis. Could you make a post about this mouse doctor ?
That’s a great idea, but shouldn’t the title be Q&A Monday Jan.1.3 ? 🤨
It’ll rather be Jan 1, Jan 2, Jan 3, Jan 4, and then Feb 1, Feb 2, etc. The Jan 1.1 was simply the last one of the monthly Q&As.
next will be 1.2
Do you think we have gone backwards with regard to our understanding of MS and how to effectively treat it? I was diagnosed when Natalizumab was approved and there was so much hope with regard to stopping MS and a future of remyelination, and even neuro-restoration. Roll forward 18 years and the very best anti-inflammatories don’t seem to stop MS – rather the neurodegeneration / smouldering MS seems to do its damage in the background. We seem no nearer to identifying the trigger and / or driver of MS. MSers want one thing – not to lose function / not to become disabled, but progressive MS (apart from those with focal inflammation) have no treatments. The wheels of the remyelination wagon appear to have fallen off – all hopes seem to be pinned on the Cambridge trial which doesn’t even start until March 2022. Am I right to feel so pessimistic or might we hear about some breakthroughs in 2022?
no
“No” he is right to feeling pessimistic or “No” we should not expect some breakthroughs in 2022?
Thanks for your insightful response. If only your tsunami of COVID 19 posts had been as short!
Sid its
Do you think we have gone backwards….answer = No
There seems to be a continuous flow of evidence that MS is caused by EBV over the last 18 years, but few neurologists seem to be paying any attention. I suspect a generation of neurologists have been indoctrinated by the un-evidenced belief that MS is a random autoimmune event. I think some of the cognitively impaired neurologists will need to retire or die before treatment can truly make progress. Meanwhile, our disease will continue to smoulder and we’ll be damaged by the dogma/EBV.
Do you think exercise or specific types such as resistance training, HIIT or steady sate cardio for example will ever be deemed a DMT for the long term treatment strategy for MS?
Probably not….my take on this would be if it does not carry a side effect risk, then it is not a potent enough effect….you can’t have it both ways so the microbiome change, vitamin D, diet x and y all fall into this problem. If proved wrong I will hold up my hands and say I was wrong but for the past forty years I have been listening to this and that quack science from quacks and academic quacks and nothing has come of it, millions have been flushed down the toilet, piles of science papers have been written and what have you got to show for it….I lot of lost hope.
Do I think exercise is beneficial absolutely…but its not a DMT
Or maybe no money can be made from it.
I know what your saying about the side effects, however I do believe a lot of factors that don’t have side effects can add up to a huge difference. For example ‘not smoking’ doesn’t have any side effects or neither does ‘smoking’ really, at least short or medium term however it can have a huge effect on progression.
There are no neuroprotective drugs in MS unless ‘anti-inflammatory’ drugs count as neuroprotective. Progression is an issue in MS independent of relapses as we know.
It would be interesting to see rates of brain atrophy, boost to mitochondria, increased energy production etc, even remylination and the holy grail of reduced EDSS with prolonged exercise.
I do believe you have to join all of these factors together, however small the benefits. Exercise could be a one of the best neuroprotectants and improver in quality of life we have but generally not promoted
Diet/exercise/meditation all worthless voodoo.
If exercise worked Lou Gehrig never would have got ALS.
I walked home from work yesterday, at a very fast pace. Took 50 minutes and I felt amazing when I got home. Refreshed and revitalised. Exercise is great.
Hello and happy new year. I’m hoping to persuade my neuro to prescribe cladribine off-label. I understand the Barts protocol is in the public domain – thanks ProfK – is there a web page where this can be seen?
May everyone’s years get brighter and better
Hello and happy new year,
I am keen to look into getting cladribine off-label, and Prof K kindly indicated the Barts protocol is in the public domain. Is there a website where one can access this?
Thank you and best wishes
Here is the link to our latest paper, containing the protocol: https://journals.sagepub.com/doi/full/10.1177/17562864211057661. It’s open access and includes the link to our patient information on slideshare.
Thank you!
Have been kindly provided with a pcr test kit for if/when I get covid.
I have low lymphocytes due to cladribine treatment – my guess they are currently 0.6
It is suggested I get anti viral medication if I get the virus and ideally as soon as possible after positive test.
Do you agree? Or should I keep fingers crossed and fight it
I am fairly healthy and had ‘fourth booster’ just after Xmas and bmi is 27 ish
Sounds like you are as well protected as possible, but antiviral medication still useful if positive/sick.
I think weekly Q&A is a brilliant move! Happy new year!
What do they call someone who does the same thing over and over again, yet expects a different outcome?
P.S. Like the new format and happy to see MD1 got his quick wit back. My favorite disclaimer to date…..“ I am not giving advice…read the papers and make up your own mind” 😂
How can I determine BVL in vivo; don’t want to give my whole brain to science yet? I’m not on any DMTs or another meds, and have to fight even for a triennial MRI down here? Don’t have clue what antibody response I may mount re: covid. I often feel totally forgotten (though you and Prof G have kindly acknowledged my swimming activities in posts over the year). As to clinic, one annual call is probably all I can expect.
BVL is one data point that AI-supported MRI reading provides. At the moment, there is no consequence emerging from BVL alone, which is why it is currently not available as part of routine follow-up (except for eyeballing/comment by the clinician).
Potential good news for progressive MS patients.
Phase 3 trail of Masitinib on the way
Firstly, Happy New Year.
In regards to the PCR test and access to anti- virals ( which didn’t even know about until I read on here ) is this only for people on the monoclonal antibodies or severely disabled or would all people with ms On dmt’s or be entitled.
Thanks
MS in general – https://www.mssociety.org.uk/what-we-do/news/ms-and-covid-19-two-new-treatments-available-mid-december
Remember ronapreve does not work against omicron.
Access to antivirals should be for anyone with risks of a bad time this could be age, co-morbidity and immunosupression/modulation should fit into that category
Thank you. I will wait and see if I get any PCR test through the door!
Research team demonstrates MRI scan in an ambulance
https://medicalxpress.com/news/2022-01-team-mri-scan-ambulance.html
50 000$
😉
https://www.healthimaging.com/topics/healthcare-economics/fda-clear-worlds-first-portable-mri
Yes, I want one.
Have to be a very very good boy and hope that Santa 🎅 brings you one next year.
🙂
https://hyperfine.io/
Interesting many years ago I worked in a place with an animal scanner as soon as the magnet went on metal objects would fly….a workmans hammer was the memorable one straight down the barrel and £10,000 worth of damage:-)
Well there some that dont mind to destroy one
In my countriy in some places we need one
I would probably be claustrophobic in that. If the technology could progress and be similar to a space helmet but leave the lower face uncovered – mouth and nose, that would be amazing and the ideal. A few more years to go for that…….
‘We can’t immunize the planet every six months,’ says vaccine scientist at Oxford
https://goodwordnews.com/we-cant-immunize-the-planet-every-six-months-says-vaccine-scientist-at-oxford/
I know that cladribine is lauded on this blog but what are the advantage of a shift from ocrelizumab to cladribine? BBB penetrant? t-cell depleter? i know that the main impact is on b-cells and this has proven not to be too effective with ocrelizumab, hence the switch. It seems that the lack of MRI activity, despite relapses (as per the definition) means that HSCT and alemtuzumab are still off the table
Advantages….convenient, safety, efficacy, CNS penetrance, COVID friendlier, etc…the question is the reason for failure. Each agent has pluses and negatives so make sure you do your homeowrok so you are satisfied with your choice
Thank you MD. I have done a lot of homework but unfortunately there are too many unanswered questions. Even the heavily trained neuros cant decide the best approach so what chance a patient. Ultimately, my decision is based on currently feeling like crap each day and increasing symptoms, which drives up my willingness to risk. I have accepted that i will never undertstand the science so its a bit of a leap of faith…..can anyone really answer the question of why ocrelizumab has failed? is my diseases t-cell driven? i have OCB, which suggests b-cell involvement. I have considered cladribine for its penetrability (is that a word?) but would be concerned that it is considered to have less efficacy that ocrelizumab and is less potent as a b-cell depleter. If the problem is already established in my CNS then alemtuzumab aint going to help with that. HSCT might but at the cost of 5-10 years reserve on top of £40k and the significant threat of covid. Sorry, turned in to a rant and not at you obviously but you can appreciate the dilemma
Is the worsening due to B cells or something else…which no MS drugs touch
As in smouldering disease? if Cladribine and the agents in HSCT dont address this then what is the benefit of the BBB penetration
https://www.biospace.com/article/releases/moderna-announces-first-participant-dosed-in-phase-1-study-of-its-mrna-epstein-barr-virus-ebv-vaccine/
Not sure if this will help people with MS.
However if it can prevent MS, it would be an amazing step
thanks
Microclots are becoming a hot topic in long covid. There are no established tests to check it though and there are only some experimental treatments (like apheresis). I wonder if microclots can be found in MS patients too, and if this is why CCSVI was bringing some symptomatic relief in MS patients like on brain fog (even if it didnt control the disease).
Being a Lifelong Musician May Protect Brain From Damage of Aging
https://multiplesclerosisnewstoday.com/news-posts/2022/01/04/being-lifelong-musician-may-protect-brain-damage-aging/?utm_source=MS&utm_campaign=ee82931cb7-RSS_EMAIL_CAMPAIGN&utm_medium=email&utm_term=0_b5fb7a3dae-ee82931cb7-71699829
AB Science OK’d to Start Masitinib Phase 3 Trial for Progressive MS
https://multiplesclerosisnewstoday.com/news-posts/2022/01/05/ab-science-okd-start-masitinib-phase-3-trial-progressive-ms/?utm_source=MS&utm_campaign=d9ef91eb46-RSS_EMAIL_CAMPAIGN&utm_medium=email&utm_term=0_b5fb7a3dae-d9ef91eb46-71699829
ntegrated Lymphopenia Analysis in Younger and Older Patients With Multiple Sclerosis Treated With Cladribine Tablets
https://www.frontiersin.org/articles/10.3389/fneur.2021.779003/full?utm_source=F-AAE&utm_medium=EMLF&utm_campaign=MRK_1799023_a0P58000000G0Y2EAK_Neurol_20220104_arts_A
This is a really good one
Want to get more myelin in your brain’
Easy stress ,stress and post traumatic stress disorder (PTSD)
extreme trauma causes the increased myelination,
At the time, scientists looking for changes in myelination related to brain disorders were focused on the cortex’s white matter, which is mostly myelinated. In multiple sclerosis, for example, an autoimmune attack destroys myelin in the white matter. Kaufer was perhaps the first to find evidence of increased myelination in the gray matter associated with disease.
Chao and Neylan did find increased myelination of neurons in the gray matter of veterans with PTSD, but not in those without PTSD. The worse the symptoms, the greater the myelination
Caneco
https://medicalxpress.com/news/2022-01-anxiety-ptsd-linked-myelin-brain.html
Doing a bit of research into HSCT and came across this post /comment:
“There are two approaches one is non ablative meaning that you can keep your immune system and here the HSCT allow you to use a bigger dose.of DMT.
The other is ablative meaning that you have a clear out of your immune system and so you need vaccinations again.
Therefore how much drug do they give CY will clear out.dividing cells but not those no dividing and the rituximab will hit B cells. So what gets rid of the t cells.
Whilst cyclophosphamide can get in the brain, rituximab wont and so
immune system in brain is not going to get touched so HSVT does not get rid of oligoclonal bands, so probably less effective in spms ppms”
Is the suggestion here that patients with OCB will not benefit from HSCT in terms of preventing their transition from RRMS to SPMS? does the non-mylo regimen not include drugs to get rid of the t-cells? if not, what is the cyclophosphamide do? why not just give rituximab. Very confusing for a patient to understand when is too far gone
These findings show that aPS/PT IgG is associated with COVID-19-associated ADEM (which can mimic MS and can help with diagnosis).
Antiphospholipid antibodies and neurological manifestations in acute COVID-19
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00350-3/fulltext
More stress =more myelin
Anxiety and PTSD linked to increased myelin in brain’s gray matter
https://medicalxpress.com/news/2022-01-anxiety-ptsd-linked-myelin-brain.html
yes I saw it-keep stressing:-)
Should I start taking adderall? I think I have minor loss in short term memory retention and cog fog
Modafinil is quite commonly used, however I recommend reading Ide Smet’s post: https://multiple-sclerosis-research.org/2021/01/the-solution-for-fatigue-getting-tired-both-of-us/
Sorry can’t give advice
https://amp.theguardian.com/science/2022/jan/08/global-spread-of-autoimmune-disease-blamed-on-western-diet
If MS is auto immune. Diets a contributing factor. Diet should always be a top priority regardless.
It sounds so easy…..
This is the best of them all …… 🙂
Drumming makes your brain more efficient
https://www.medicalnewstoday.com/articles/327279?utm_campaign=2022-01-02_Drumeo_Mainlist_Brain-On-Drums&utm_medium=email&utm_source=customer.io
B cells
Human B cell lineages associated with germinal centers following influenza vaccination are measurably evolving
https://elifesciences.org/articles/70873?utm_source=content_alert&utm_medium=email&utm_content=fulltext&utm_campaign=10-January-22-elife-alert
Autoimmunity may explain long COVID and rare vaccine side effects
https://www.medicalnewstoday.com/articles/autoimmunity-may-explain-long-covid-and-rare-vaccine-side-effects
Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain
https://www.biorxiv.org/content/10.1101/2022.01.07.475453v1
After many years of finding blood tests painful, today I found out about Emla cream to numb the skin first, (lidocaine & prilocaine), available over the counter.
🙂
EbV
Epstein-Barr virus may be leading cause of multiple sclerosis
https://medicalxpress.com/news/2022-01-epstein-barr-virus-multiple-sclerosis.html
“MS is a relatively rare disease, and the onset of MS symptoms begins about ten years after EBV infection”
So the problem i have with this is pediatric ms
The youngest age of onset of MS in the medical literature is 2 years
https://consultqd.clevelandclinic.org/multiple-sclerosis-in-the-very-young/
How do we square the fact that Ebv as time to infect memory b cells of a 2 years old child an allmost
imediately develop ms
Also a 2 year old does nt seem to have manny memory b cells yet
We also observed a gradual slight increase in the percentage of CD27+ IgD+ B-cells, whereas the percentage
of
CD27+ IgD- B-cells increased more rapidly between the 6–18 months and 18 months to 4 years age groups, reaching a peak at the age of 8–12 years before stabilizing
B-cell subpopulations in children: National reference values
doi: 10.1002/iid3.26
ppms
Study finds hydroxychloroquine delays disability for least treatable form of multiple sclerosis
https://medicalxpress.com/news/2022-01-hydroxychloroquine-disability-treatable-multiple-sclerosis.html
Any comments on the following paper? Saw a comment on Twitter that it’s maybe the most convincing data yet that EBV is the cause of MS.
https://www.science.org/doi/10.1126/science.abj8222
Good news, and antivirals should be developed. But will they and also EBV causing MS is kind of old news.
However if it becomes more mainstream then more treatments may come along.
Good news for MS patients and people who would of gone on to develop MS but don’t possibly through an EBV vaccine
More interest in targeting EBV Tevogen Bio is now also interested in targeting ebv for multiple sclerosis. Could you make a post about this mouse doctor ?
Link : https://www.businesswire.com/news/home/20220120006016/en/Tevogen-Bio™-to-Study-Potential-Use-of-its-T-cell-Technology-in-Epstein-Barr-Virus-and-Multiple-Sclerosis
Not really as there is not enough info but atara has competition it is labelled as disruptive technology .. .em
Okay I understand. 🙂 Also, could you send this to professor Gavin Giovannoni he might want to reach out to them. 🙂 ?
Will do but he will be conflicted if he has anything to do with atara but motto is in bed with all of them or none of them