This reminds me, there is a small study made at a usa University on a patient which seemingly started having ms symptoms and they started her on acyclovir or vanacyclovir (i cant quite recall) and treated rhe symptoms successfully. But she had to stay on it if i remember rightly.
Once she had demonstrated improvement with the treatment she should have continued on the medication. EBM is defined as, “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients”. The best evidence in an individual is the effect a particular treatment has had on that individual. If gold injections cause kidney failure, you don’t continue them in that individual regardless of what any meta analyses or RCTs say about efficacy. This individual improved with HAART so it would be indefensible to stop it. If there are no systematic reviews of randomised controlled trials (RCTs), individual RCTs with narrow confidence intervals, systematic reviews of cohort studies, individual cohort studies, low-quality RCTs, systematic reviews of case-control studies, case-controlled studies, case series and poor-quality cohort or case-control studies then case reports trump ‘expert’ opinion. So all neuros who claim to follow EBM should be offering to treat all MS patients with HAART until higher quality evidence exists. Because Bolam was superseded by Bolitho it is no longer an adequate medicolegal defence to say, “I’m justified in not prescribing HAART because a representative body of my peers act the same way”. Eventually, an enterprising lawyer will bring a class action lawsuit against neurologists who are ignoring the case reports and not acting in the best interests of patients. There are about 7000 pwMS in the UK and if only 1:10 have lost an average of £100,000 over the last decade, that comes to £70 million in damages in the UK alone.
Here's another one: amantadine is an antiviral afair originally made for flu. After it lost its efficacy for flu it got repurposed, heh.
It's available on the nhs for ms related fatigue.
"Amantadine as an antiviral drug is one of the suggested interventions for management of fatigue. Although not clearly defined, amantadine might affect MS-associated fatigue through its antiviral function, immune-mediated mechanism, or an amphetamine-like activity."
I asked my neuro because i wanted to see what he'd say 'what's the mechanism?' He said we dont really know. "I know (!)" I thought.
It's quite plain to me at this point and with this brain (took me a while) that arvs were not employed in studies on purpose for a long time therefore cases like hers were just anecdotes.
I've forgotten the other thing I was gonna add.
Hey, nevermind though - let's have some hot cocoa it's good for ms /s. Oh and apparently ms fatigue is real, another study concluded. Who'd have guessed (!) That when your brain is inflamed and your meninges are set to explode that you'd feel 3/4 dead 👍 they just keep wasting money on useless studies, it boils my blood.
I haven't got a clue. But the sincerity with which she speaks in the video is striking. I first looked it up when i got diagnosed and she also writes some columns i think for the ms society. You could ask her? She's also on twitter. I havent the brain power to chase it up.
HAART licences have started to expire, so pharma can’t make a fortune treating pwMS with HAART. Pharma can make a fortune from keeping us in need of the immune suppressants. As the CD20 antibodies become generic, I’m sure that the Bruton’s kinase inhibitors will be shown to offer marginal benefits (with an incremental cost effectiveness ratio just below £20k - the unofficial NICE cut off). I’ve just finished the book, ‘bad pharma’, and would recommend this to everybody.
I can think of hypotheses for the pregnancy question, but can’t think how to test these.
Re: "if pregnant (and breastfeeding ?!) women keep MS at bay during their pregnancy, what happens to the viral hypothesis during that time?"
MS doesn't go away during pregnancy only the immune response to MS is changed. I suspect the immune response to the virus is also altered. But to be honest I don't know.
$5 - $7 million sounds like a small investment compared to the cost of other trials.
I would be interested in participating in a trial that involves an antiviral drug that has multiple years of studies showing that it has long term safety and no negative impacts for PwMS.
Currently when people with ms get Covid we are prescribed , if I am not mistaken, an anti viral that was used to treat HIV. Is that anti viral similar to the ones you have mentioned that may prevent further deterioration in MS.
This is a different antiviral. The HIV antiviral is to slow down the breakdown of the antiviral that targets the Coronavirus and it is not in itself working against SARS-CoV-2.
Well I'm wondering too. But since the ms charities seemingly are busy studying weather chocolate benefits pwms i suppose we'll have to die some more a bit first.
US trial for Tenofovir for MS was suspended due to lack of funding. This is another fairly inexpensive, well-tested anti-viral drug. Do you have any insights as to whether this drug holds promise?
Sandra, didn’t know there even was one! But, then, I’m fairly cynical. There must be quite a large financial return here in the states to look at relatively inexpensive solutions. Just my opinion.
The question " would you participate" has a pretty obvious answer. If someone is intelligent enough to sign upto your blog and read the entire post, its an easy assumption they are intelligent enough to realise haarts are currently our best hope. I would participate in a heartbeat 😉 but do wonder if an open minded hemo could prescribe after hsct as ermmmm prophylaxis ? 😅
Yes I’d definitely take part in such a study and the cost is expensive but worth it to move forward. Has anyone ever questioned if non responders to HSCT were EBV positive?? If EBV Negative pre HSCT was the success rate better?? Something I’ve wondered for a while post my own HSCT.
I'd like to have more infos from Prof G about remyelination drugs and trials, without that I think there is no cure and no improvement especially for spinal injuries.
If as is stated in the trial Tenofovir is just another name for Ocrevus ( which I have been on for 4 years and certainly can,t climb stairs wonderfully well ) I cannot understand why drug companies are refusing to trial drugs that show promise I firmly believe that you are as usual doing all you can to encourage trials But just look at all the interest and response you get on here why not put out a request to all your followers what if we wrote as a community do you feel that would help in any way? I would be more than happy to participate in any trials I am more than willing to be a guinea pig if anything works on this horrible illness to make the future look better for our children and theirs thank you once again for keeping us up to date on so many things if I relied on my Neuro I wouldn't learn half as much
Tenofovir is a nucleotide reverse transcriptase inhibitor (https://en.wikipedia.org/wiki/Tenofovir_disoproxil#/media/File:Tenofovir_disoproxil_structure.svg). Ocrevus in an anti-CD20 antibody. They are not the same thing. So, both should be trialed together as they are likely to have an additive effect. I think the antivirals have the potential to reverse MS to an extent rather than just slowing or stopping it’s progression.
Hi Prof G, I think EBV antivirals will stop the progression of the disease, can you make the point about remyelination drugs. Recreating myelin sheaths should be considered a cure?
I’m not well-versed in Pharma budgeting but the amounts presented don’t sound high at all. To answer the question, yes I would participate given that it’s safe to do so.
Which would you say are the main barriers at the moment to these trials happening?
HAART might work, costing Pharma £billions of lost revenue. Have no doubt that the companies making Natalizumab and Ocrelizumab will have discussed how to impede this research.
Would the NIHR or the MS society fund a study of AZT in MS initially? This crosses the bbb. This would not upset Pharma as an add on to their current treatments and it would not mess up all the pre-existing calculations of ICER for their products. Ocrelizumab costs £19,160pa plus 2x day medical unit costs, Ofatumumab is £19,402.50pa plus a few sharps boxes, Natalizumab is £14,690pa plus 13x day medical unit costs and generic AZT is £162pa (source BNF). I suggest doing a small trial initially as an add on therapy and ensure assessment technique can identify improvements in function rather than just decreased frequency of relapses. I would restrict it to EDSS 5.0 - 8.5 because it will be easier to identify improvement and these people can be brought in to participate in assessments (or remote video assessments). If it helps within 6 months the study can be extended to ensure any benefit endures. The risk is that EBV mutates and escapes chemical control (as HIV has). If it is effective, other antivirals (perhaps suggested by a GUM specialist with knowledge of HAART) could be tested and participants with a wider range of disability. After that, the head to head studies that will hit Novartis, Biogen, Sanofi and Roche, but if they see the writing on the wall, they will develop more effective HAART to plug some of the gap.
We are going to try and set-up an international study, which will include the UK as a participant. However, post-COVID research priorities have changed and I am not sure MS will be at the top of the pile.
Acute CoVID triggered my last relapse and my subsequent increased fatigue could be called long CoVID or MS. My neurologist has agreed to test my EBV viral load because I suspect a more accurate description would be EBV reactivation. When I’ve got this result, the next hurdle will be persuading somebody to prescribe off label zidovudine 250mg bd.
I think treating EBV with antivirals should put MS in remission, maybe one day we'll know. In march 2020 I got tingling on my hands, surely I got Long Covid but at that time Italy was in lockdown and test for covid was not possible, only if you went in the hospitals. It started with fever at 37.5* C, peevish cough, GI issues, cog fog, etc, For a month I had dyspnea and I remyelinate, after 15 months on June 2021 I got a bad relapse meanwhile two herpes simplex on my lips, I don't know if there is correlation. I've been diagnosed on October 2021. I don't know how much time MS was with me and I don't know if it's been "benign" for years, because they found about 30 lesions on brain and 2 on spine, most bigger and symptomatic is 23 mm located on C2-C3.
I wouldn’t be a proper subject for such a trial, but I find it enormously important, since it could potentially stop the ravages of MS at an early point. As an older patient, the most I can do is take antivirals, but I’m cheering on a study. Repeat repeat! I very much appreciate your persistence.
Excellent question!! I suppose off license prescription would work? I'd do it. Perhaps the gods of off license prescriptions need to be appeased by say...a petition? Or...some such.
I’ve been prescribed medication off label before - it’s not uncommon. The reality is that people are completely losing their quality of life, becoming disabled, in constant pain. You only get one life and watching it slowly deteriorate due to MS is heartbreaking. Letting people get into that state when you could help them with a drug that has already passed safety trials for another condition is surely more unethical. People need help now - it could be too late for them to regain any meaningful quality of life after the years it takes for a clinical trial.
Its a tough one because pwms were told for years that: 1.antibiotics dont work 2. Retrovirals do not work.
But sign me up.
Here s an interesting anecdote: https://www.bbc.co.uk/news/uk-england-sussex-34659771
Thanks Anna. I took a gander. That’s fascinating!
Have the HIV drugs continued to work? The film is 7 years old
No she only took it for a short period of time, I.e. to cover her as part of a post-exposure prophylaxis protocol.
I read her twitter feed this morning and she is back in a wheelchair
Aw. Yeah, she took a short course only.
This reminds me, there is a small study made at a usa University on a patient which seemingly started having ms symptoms and they started her on acyclovir or vanacyclovir (i cant quite recall) and treated rhe symptoms successfully. But she had to stay on it if i remember rightly.
Quite, i remember now.
So this begs the question: what stops us as patients from having potential exposure quite a few accidental encounters? 😂👍
Once she had demonstrated improvement with the treatment she should have continued on the medication. EBM is defined as, “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients”. The best evidence in an individual is the effect a particular treatment has had on that individual. If gold injections cause kidney failure, you don’t continue them in that individual regardless of what any meta analyses or RCTs say about efficacy. This individual improved with HAART so it would be indefensible to stop it. If there are no systematic reviews of randomised controlled trials (RCTs), individual RCTs with narrow confidence intervals, systematic reviews of cohort studies, individual cohort studies, low-quality RCTs, systematic reviews of case-control studies, case-controlled studies, case series and poor-quality cohort or case-control studies then case reports trump ‘expert’ opinion. So all neuros who claim to follow EBM should be offering to treat all MS patients with HAART until higher quality evidence exists. Because Bolam was superseded by Bolitho it is no longer an adequate medicolegal defence to say, “I’m justified in not prescribing HAART because a representative body of my peers act the same way”. Eventually, an enterprising lawyer will bring a class action lawsuit against neurologists who are ignoring the case reports and not acting in the best interests of patients. There are about 7000 pwMS in the UK and if only 1:10 have lost an average of £100,000 over the last decade, that comes to £70 million in damages in the UK alone.
I had to reread your reply for about 30m lol and reread the tests lol
I see your point; I'd be interesting to find out how many pwms requested emergency arvs themselves after reading that article.
https://clintransmed.springeropen.com/articles/10.1186/s40169-019-0239-4
Here's another one: amantadine is an antiviral afair originally made for flu. After it lost its efficacy for flu it got repurposed, heh.
It's available on the nhs for ms related fatigue.
"Amantadine as an antiviral drug is one of the suggested interventions for management of fatigue. Although not clearly defined, amantadine might affect MS-associated fatigue through its antiviral function, immune-mediated mechanism, or an amphetamine-like activity."
I asked my neuro because i wanted to see what he'd say 'what's the mechanism?' He said we dont really know. "I know (!)" I thought.
It's quite plain to me at this point and with this brain (took me a while) that arvs were not employed in studies on purpose for a long time therefore cases like hers were just anecdotes.
I've forgotten the other thing I was gonna add.
Hey, nevermind though - let's have some hot cocoa it's good for ms /s. Oh and apparently ms fatigue is real, another study concluded. Who'd have guessed (!) That when your brain is inflamed and your meninges are set to explode that you'd feel 3/4 dead 👍 they just keep wasting money on useless studies, it boils my blood.
I haven't got a clue. But the sincerity with which she speaks in the video is striking. I first looked it up when i got diagnosed and she also writes some columns i think for the ms society. You could ask her? She's also on twitter. I havent the brain power to chase it up.
I am a follower of her so I will contact and find out but it is very unlikely to happen until weekend assuming I remember
So if I were to be infected with HIV tomorrow and treated with anti-vials, I would be running my own HAART trial with a sample of 1?
p.s. I would be willing to take anti-virals post-alemtuzumab if risk profile permits.
2 questions from my wife:
1) if we have known for a while now that HIV+ MSers do well, why haven't HIV drug makers run a trial yet to repurpose their drugs?
2) if pregnant (and breastfeeding ?!) women keep MS at bay during their pregnancy, what happens to the viral hypothesis during that time?
Her words, I promise. Couldn't answer those so here you are.
Re: "if we have known for a while now that HIV+ MSers do well, why haven't HIV drug makers run a trial yet to repurpose their drugs?"
We did a small study about 7 years ago and have been trying to get them interested, but to no avail. It is not for lack of trying.
HAART licences have started to expire, so pharma can’t make a fortune treating pwMS with HAART. Pharma can make a fortune from keeping us in need of the immune suppressants. As the CD20 antibodies become generic, I’m sure that the Bruton’s kinase inhibitors will be shown to offer marginal benefits (with an incremental cost effectiveness ratio just below £20k - the unofficial NICE cut off). I’ve just finished the book, ‘bad pharma’, and would recommend this to everybody.
I can think of hypotheses for the pregnancy question, but can’t think how to test these.
Do drugs licenses not get recycled if they get repurposed? Something along those lines, cog fog.
Re: "if pregnant (and breastfeeding ?!) women keep MS at bay during their pregnancy, what happens to the viral hypothesis during that time?"
MS doesn't go away during pregnancy only the immune response to MS is changed. I suspect the immune response to the virus is also altered. But to be honest I don't know.
Excellent point.
$5 - $7 million sounds like a small investment compared to the cost of other trials.
I would be interested in participating in a trial that involves an antiviral drug that has multiple years of studies showing that it has long term safety and no negative impacts for PwMS.
Currently when people with ms get Covid we are prescribed , if I am not mistaken, an anti viral that was used to treat HIV. Is that anti viral similar to the ones you have mentioned that may prevent further deterioration in MS.
This is a different antiviral. The HIV antiviral is to slow down the breakdown of the antiviral that targets the Coronavirus and it is not in itself working against SARS-CoV-2.
Yes I would participate. What response are you getting from the established MS charities?
Well I'm wondering too. But since the ms charities seemingly are busy studying weather chocolate benefits pwms i suppose we'll have to die some more a bit first.
US trial for Tenofovir for MS was suspended due to lack of funding. This is another fairly inexpensive, well-tested anti-viral drug. Do you have any insights as to whether this drug holds promise?
I cant believe that got cancelled :( i had high hopes.
Sandra, didn’t know there even was one! But, then, I’m fairly cynical. There must be quite a large financial return here in the states to look at relatively inexpensive solutions. Just my opinion.
https://clinicaltrials.gov/ct2/show/NCT04880577
Took a look. RRMS, 60 participants, no funding…. :(
The question " would you participate" has a pretty obvious answer. If someone is intelligent enough to sign upto your blog and read the entire post, its an easy assumption they are intelligent enough to realise haarts are currently our best hope. I would participate in a heartbeat 😉 but do wonder if an open minded hemo could prescribe after hsct as ermmmm prophylaxis ? 😅
Yes I’d definitely take part in such a study and the cost is expensive but worth it to move forward. Has anyone ever questioned if non responders to HSCT were EBV positive?? If EBV Negative pre HSCT was the success rate better?? Something I’ve wondered for a while post my own HSCT.
Very encouraging talk. The anti vitals are very tempting.
I'd like to have more infos from Prof G about remyelination drugs and trials, without that I think there is no cure and no improvement especially for spinal injuries.
If as is stated in the trial Tenofovir is just another name for Ocrevus ( which I have been on for 4 years and certainly can,t climb stairs wonderfully well ) I cannot understand why drug companies are refusing to trial drugs that show promise I firmly believe that you are as usual doing all you can to encourage trials But just look at all the interest and response you get on here why not put out a request to all your followers what if we wrote as a community do you feel that would help in any way? I would be more than happy to participate in any trials I am more than willing to be a guinea pig if anything works on this horrible illness to make the future look better for our children and theirs thank you once again for keeping us up to date on so many things if I relied on my Neuro I wouldn't learn half as much
Tenofovir is a nucleotide reverse transcriptase inhibitor (https://en.wikipedia.org/wiki/Tenofovir_disoproxil#/media/File:Tenofovir_disoproxil_structure.svg). Ocrevus in an anti-CD20 antibody. They are not the same thing. So, both should be trialed together as they are likely to have an additive effect. I think the antivirals have the potential to reverse MS to an extent rather than just slowing or stopping it’s progression.
Hi Prof G, I think EBV antivirals will stop the progression of the disease, can you make the point about remyelination drugs. Recreating myelin sheaths should be considered a cure?
I’m not well-versed in Pharma budgeting but the amounts presented don’t sound high at all. To answer the question, yes I would participate given that it’s safe to do so.
Which would you say are the main barriers at the moment to these trials happening?
HAART might work, costing Pharma £billions of lost revenue. Have no doubt that the companies making Natalizumab and Ocrelizumab will have discussed how to impede this research.
I subscribe to thit line of thinking, me as well as every pwms I've ever talked to lol
Would the NIHR or the MS society fund a study of AZT in MS initially? This crosses the bbb. This would not upset Pharma as an add on to their current treatments and it would not mess up all the pre-existing calculations of ICER for their products. Ocrelizumab costs £19,160pa plus 2x day medical unit costs, Ofatumumab is £19,402.50pa plus a few sharps boxes, Natalizumab is £14,690pa plus 13x day medical unit costs and generic AZT is £162pa (source BNF). I suggest doing a small trial initially as an add on therapy and ensure assessment technique can identify improvements in function rather than just decreased frequency of relapses. I would restrict it to EDSS 5.0 - 8.5 because it will be easier to identify improvement and these people can be brought in to participate in assessments (or remote video assessments). If it helps within 6 months the study can be extended to ensure any benefit endures. The risk is that EBV mutates and escapes chemical control (as HIV has). If it is effective, other antivirals (perhaps suggested by a GUM specialist with knowledge of HAART) could be tested and participants with a wider range of disability. After that, the head to head studies that will hit Novartis, Biogen, Sanofi and Roche, but if they see the writing on the wall, they will develop more effective HAART to plug some of the gap.
We are going to try and set-up an international study, which will include the UK as a participant. However, post-COVID research priorities have changed and I am not sure MS will be at the top of the pile.
Long CoVID is also related to EBV, so CoVID should stimulate more interest than ever.
I think Long Covid is a trigger for MS because it reactivates EBV and causes relapses
Acute CoVID triggered my last relapse and my subsequent increased fatigue could be called long CoVID or MS. My neurologist has agreed to test my EBV viral load because I suspect a more accurate description would be EBV reactivation. When I’ve got this result, the next hurdle will be persuading somebody to prescribe off label zidovudine 250mg bd.
I think treating EBV with antivirals should put MS in remission, maybe one day we'll know. In march 2020 I got tingling on my hands, surely I got Long Covid but at that time Italy was in lockdown and test for covid was not possible, only if you went in the hospitals. It started with fever at 37.5* C, peevish cough, GI issues, cog fog, etc, For a month I had dyspnea and I remyelinate, after 15 months on June 2021 I got a bad relapse meanwhile two herpes simplex on my lips, I don't know if there is correlation. I've been diagnosed on October 2021. I don't know how much time MS was with me and I don't know if it's been "benign" for years, because they found about 30 lesions on brain and 2 on spine, most bigger and symptomatic is 23 mm located on C2-C3.
I wouldn’t be a proper subject for such a trial, but I find it enormously important, since it could potentially stop the ravages of MS at an early point. As an older patient, the most I can do is take antivirals, but I’m cheering on a study. Repeat repeat! I very much appreciate your persistence.
Bring on the study - where do I sign up?
What prevents you from prescribing HAART to your patients now without a trial? From what you say, the potential benefits seem to outweigh the risks
Excellent question!! I suppose off license prescription would work? I'd do it. Perhaps the gods of off license prescriptions need to be appeased by say...a petition? Or...some such.
It’s considered ‘off label’ prescribing and you might get struck off for conducting unapproved research on patients.
I’ve been prescribed medication off label before - it’s not uncommon. The reality is that people are completely losing their quality of life, becoming disabled, in constant pain. You only get one life and watching it slowly deteriorate due to MS is heartbreaking. Letting people get into that state when you could help them with a drug that has already passed safety trials for another condition is surely more unethical. People need help now - it could be too late for them to regain any meaningful quality of life after the years it takes for a clinical trial.