You may be interested in watching this online lecture I gave a week ago. It explains why relapses and focal MRI activity (Gd-enhancing lesions and new or enlarging T2 lesions) are not MS and why we need to focus on new therapeutic targets.
CoI: multiple
Watched the lecture (similar to one you have given before).
I’d like an honest answer – when will things change so that therapies are available to address the real MS?
I suspect your take on the real MS, which I totally agree with, will ruffle some feathers, you’ll get invited to some X v Prof G debates, you’ll still sit on the boards of various MS drug trials (drugs which you accept don’t address the real MS), you’ll oversee the work of PhD students writing a thesis on Copaxone v Interferon….. but will patients stop becoming more disabled in the next 5-10 years as a result of your assessment of what MS is?
Please don’t say that science is a slow process or use that quote about new ideas being vehemently opposed, then xxx, then accepted.
I find it scandalous that after 50 years of research we are now finding out about the real MS and that all the tens of billions of $ spent on anti-relapse drugs didn’t make a jot of difference to the real MS or patient outcomes.
I wonder if this campaign (to highlight the real MS) will be similar to the BLM campaign – lots of protesting, pulling down of statues, some token changes… and nothing really changes in the long run (the status quo is maintained).
Let’s walk the talk. We are doing the following to address smouldering MS:
1. A trial of cladribine in progressive MS to see if it targets CNS B cells.
2. A trial of a proteosome inhibitor to try and scrub the brain clean of B-cells and plasma cells
3. A trial of famciclovir in MS as a step to a larger trial to target EBV
We are also trying to get funding for our proposed (4) pioglitazone add-on to DMF study, (5) iTeri study, (6) OXO study and (7) HAART study. These all are addressing smouldering MS. As a unit, and me personally, only have so many hours in a day.
THANK YOU.
Fingers crossed that one of these trials comes up trumps. All MSers want one thing – to stop worsening disability (whatever EDSS they are). A drug that does this is the holy grail.
I know about the first trial i.e. the chariot trial but where can I find out about second and third trials on your list?
If I recall correctly I saw some slides on this forum few moths a go for add on proposals of Dmf * metformin/clemastine, now some months later I read about dmf + pioglitazone. Did your insights changed last months?
You are mistaken metformin is the idea and work of other groups
Bear,
Your post is excellent for bringing in perspective. The big picture gets lost very quickly when news clips are so readily accepted as the way things are done.
The health system, those who make their living from it, and those who go to it for help must all play an equal part in disease or physiological conditions. The hierarchical glamour has to go.
My question, on the heels of your point, is where is the action on a cure for MS? Why so much on management of MS? There are cures (I cured mine 15 years ago) but it was an intensive process. The mechanism lay in the procedure and not so much the ingredients. I liken it to making bread where the ingredients are really simple and few but success lies in how to do it. It’s a tragedy that the MS fix is being sought in quick injections or pills –as though ease and convenience were the goal. The healing arts should be an art: employing materials along with with method, care and patience. There are probably several ways to cure MS but you can bet these ways are as dowdy as handwashing. The way I cured mine involved GABA which is the major inhibitory neurotransmitter in the adult brain and the excitatory neurotransmitter in child’s brain. Think of the amount of tweaking to get the balance right. I didn’t use worms (as I read the other day!) but I did rely on the herpes simplex virus (1) and a kind of yeast. The biggest component was time and devotion supporting the fact that if you want something done well you have to do it yourself.
Dear Sid
Science is a slow process and if it needs class I evidenc, which the regulators insist on then it needs double blind trials. They takes 3-5 years to do and then it takes 1-2 years to go through the regulatory process.. You know this….and things will not change unless you overhaul this system.
Do that and you get the hydrochloroquine fiascos
“new ideas being vehemently opposed, then xxx, then accepted”…The reality is just this..
“spent on anti-relapse drugs didn’t make a jot of difference to the real MS or patient outcomes” but surely you were making the point for your alter ego that you have been curedby alemtuzumab and therefore you are a product of the money spent and I am sure you think that it is money well spent.
MD,
It’s Sydney not Sid (Sid to my friends).
I never said I’ve been cured by Alemtuzumab – it has stopped any more relapses (13 years) and MRIs show no activity. But I have deficits from prior to my treatment and can’t be sure if slow burn is continuing.
Science isn’t slow – researchers and research processes and procedures are slow. I want you to go out with a bang – a cheap neuroprotective drug which you prove works and can be taken up quickly as it is a repurposing of an existing drug. I don’t want to see you at 70, sitting on your rocking chair in a village outside Huddersfield reminiscing about failed cannabis trials or thinking about all those little orphaned mice in Dr Barnados homes. At least you’ll have Welsh Mouse to keep you company – listening to Max Boyce albums and checking IP addresses. Perhaps G will visit you, or perhaps he’ll be on his luxury yacht off St Tropez. I’ll visit you as underneath we’re all decent folk.
Sorry thought.your name was Sid Cupp.
Gave.you cheap neuroprotective on Thursday what should we be doing with that one. How many more do we need to give
Science is a slow process and if it needs class I evidenc, which the regulators insist on then it needs double blind trials. They takes 3-5 years to do and then it takes 1-2 years to go through the regulatory process.. You know this….and things will not change unless you overhaul this system.
No its not. With advances in AI and gene sequencing its a rapid pace. If not explain to why COVID vacibe can be developed in 6 months. Times r changing…..
Why COVID vacibe can be developed in 6 months…Well first off I’m still waiting and havent had anything yet…but to explain why is easy.
COVID is killing people..So the typical route for safety assessment has been bent….but still where are the vaccines they were made months ago. Change the regulators and the regulatory process and you get change. However, if you need to show efficacy in a neurological condition that progresses at a very slow rate the trials are with long or they have to be massive…this is simple biology. In a covid study with fatality as an enpoint it is 1 month per person not 5 years.
..Which bit of gene sequencing is going to work wonders? You have identical twins one is asymptomatic the other is knackered why?
One the theories out there about the universe is that its pixilated. Implying we are living in a simulation. The experiment currently using Halometer to prove this. The point Im trying to make is you can model anything including biological process using sufficient computing power and memory.
Way to miss the point.
How are you going to prove anything in chronic diseases which almost by definition come with slow progression without waiting a few years? With an AI magic wand?
Tired of false hopes and promises. We both know ms is a cash cow pharma is not going to slaughter for ethics. Let’s start being honest with patients. I bet you 10 years from now we will be having the same discussion and posts. Until a phase 3 trial is funded. Nothing is going to change.
2. A trial of a proteosome inhibitor to try and scrub the brain clean of B-cells and plasma cells
3. A trial of famciclovir in MS as a step to a larger trial to target EBv
PROF G can I have more information about these two trials above. Are they under way or recruiting ? Who are they for ?
Prof G, if possible, could you briefly explain how the iTeri study addresses smoldering MS?
And on a side note, thank you for all the hard work and continued dedication. Some of us do really APPRECIATE this blog and the unbiased information it provides!
Teriflunomide is a broad-spectrum antiviral with activity against EBV and likely HERVs. The idea is to induce with a B-cell depleting agent and maintain with teriflunomide a safer DMT.
Re: “unbiased information”
I doubt it; we are as conflicted as any others in the field and bring our biases to the site. For example, just this week MD was accused of being biased against alemtuzumab. We have also being accused of being too pro-cladribine. Just two examples and sure there are more.
Are you saying being on a DMT is not helping us in the long run? Is being on one a waste of money?
this was also my question for those with MS. it is a very scary thought for those with MS that they may have a disease smoudering and not know about it until it has progressed too much or that the drugs they have been taking will do no good in the long run?
What would you suggest to MS patients in terms of how they approach their neurologist about this? As you are aware I am sure neurologist vary greatly on how they approach the treatment of MS.
Annom this question is an existential question and I think most neurologists know that a certain proportion of their patients are going to develop SPMS at some point. What they don’t know is what is going to happen to their patients treated very early who are NEDA and stable. We all live in hope. This question also applies to the general population and hence all of us in that life is an age-related neurodegenerative disease. If we live long enough we are all going to develop a progressive neurological condition. Some of us are able to factor this into our time horizons, but others not.
Thanks, really informative presentation.
Any idea how brain volume loss of the highest dose anti CD20 quartile compares to alemtuzumab and natalizumab?
No, but I have asked for it!
Is there any update on that specific data?
2. A trial of a proteosome inhibitor to try and scrub the brain clean of B-cells and plasma cells
3. A trial of famciclovir in MS as a step to a larger trial to target EBV
PROF G
Can you give details of these trials please
Are they still recruiting and who is eligible?
Thanks
Prof G,
Thank you for the video. You presented a couple of studies where anti-CD20 drugs (rituximab and teriflunomide) showed the best evidence of fighting the underlying disease. After an IRT such as alemtuzumab or HSCT, would you suggest patients immediately begin an anti-CD20 drug, despite currently experiencing NEDA?
Thank you
My commendation, Professor G, of analyzing and collating, with presented data, what the “Real MS” is, after all your years of clinical experience, deep analytical thought, and your strong immunology training. At this point in time, for existing MS patients, it appears that your slide on the treatment pyramid, along with a healthy “ holistic” lifestyle, is the best bet for efficacy and safety for MS patients at this point in time. Initially a powerful antiadaptive, peripheral, anti inflammatory DMT, to quell the 10-15 years of this phase ( agreed, not the real MS, just the response of relapses being ”invited in” from the brain and cord ) that can lead to short term disability ( not long term disability ) and epitope spreading. These agents are not safe over the long term in an aging MS patients’ immune system. And, other than Cladribine and S1P’s, don’t penetrate the CNS well enough. So retire these DMT’s after the initial peripheral waves of B and T cells, as generally, for most patients, “ “job well done”( but do switch strong anti inflammatories early if not doing the job, which usually works, in my experience, with my 900 MS patients ). Then Teriflunomide ( (an “exquisite“ drug for MS ), thereafter, for the long haul—a CNS penetrant, cytostatic, not cytotoxic, immunomodulatory, not immunosuppressant, end organ protector, causing reduction of superficial and deep cortical, and likely, cord atrophy, with “broad” antiviral effects( your right—EBV infected B cells, altering B cell behavior for the worse, in a smoldering CNS EBV environment, or HERV, rather than early EBV, in genetically prone pediatric MS). The only time B cells can present antigen, without T cell help, is when B cells are chronically bathed in a smoldering, lower grade, CNS inflammatory environment ( MS for years before the patient was diagnosed)and therefore B cells, which can be 10,000x stronger cognate antigen presenters, as you well know, to naive T cells, can take Brain and cord altered varied CNS cell antigens ( not recognized as “ self” ), via lymphatics, or through the extensive brain and cord bathing CSF, to deep cervical nodes, and set up the trafficking pathological clone for ever after.( Inside/Out pathophysiology ). So we are all waiting for the “treatment sandwich” of inexpensive, immunologically safe, CNS penetrant, existing, generic meds, or natural substances, that can be repurposed for a ”new career” in end organ MS protection— i.e.,, alpha lipoid acid; simvastatin; clemastine; sodium channel blockers; etc., etc. Lastly, as you have always correctly proposed, a healthy diet, with periodic fasting and decreased caloric intake( has worked very well on a handful of my MS patients who can fight their gastronomic cravings of unhealthy, good smelling, and tasting, food —one doesn’t feel so great after eating too much of this type of food— doesn’t the body tell you something?), plus steady exercise. I apologize to you and your blog readers for getting verbally carried away and do understandably open myself to disagreement and criticism for sticking my neck out on your blog, for which I value every entry from you, Dr Baker, Dr Gnanapavan and occasionally Dr Schmierer and others.
Respectfully, from your descendant over the pond, in Reading, Pennsylvania.
Clifford Reed MD Neurology
Excellent food for thought!
Any idea as to why some people treated early with Alemtuzumab or HSCT are both ‘cured’ of active focal inflammation as well as smoldering MS?
How can you see the smoldering MS? Do you have to have lesions first?
Re: “How can you see the smoldering MS? Do you have to have lesions first?”
Yes, we think you have to have lesions first. However, there is early evidence that SELs (slowly expanding lesions) may start off as a tiny lesion and just expand with time, i.e. they form as a primary lesion.
With that in mind how do you suggest people tackle making sure their neurologist looks for this? What should they say to their neurologist?
Do do F***ing reading and smell the roses:-)
I don’t think this is helpful for a patient, they don’t know what to ask for? I am asking for more of a specific and approporate dialog example to pass on to those I know with MS – so they can speak to their neurologist and explain what they feel should be done to look for this?
Sorry for my levity, ProFG has to answer your question not me.
Can you please clarify how smoldering MS is found? is this underneath existing lesions and seen on MRI?
And are you saying current treatments are no good for this at all and will make no difference in the long run to the final progression of Ms unless things stay the same?
Also on a seperate note – How can people in the current day with COVID see top neurologists such as you when even private practices are not seeing patients currently?
Re: “Can you please clarify how smouldering MS is found?”
Clinically it manifests as clinical worsening independent of relapses or PIRA. On MRI it can be seen as accelerated brain or grey matter atrophy or the expansion of lesions on MRI (slowly expanding lesions). These things are not routinely monitored in clinical practice.
So if neurologist were to look at an MRI and see these signs typical of smouldering MS does that mean yes normal treatments will not work because this patient is beyond simple inflammation or do you believe current treatments will work anyway but I’m not approved by nice?