I'm 56. I'll be dead before anything comes to market to help me lol. Good news for those coming up behind though and those who haven't yet been diagnosed.
Please can I have some Frexalimab. I have been reading about MS research since I was diagnosed age 30 when my son was 2. He is now 38 and I have just filled in the form to claim my state pension. Just give me the drugs.....PX
I think my comment got dropped when I edited one? My brain is smouldering away! In any event, the gist was I am far too old for this, but I’m extremely excited by this research. I also appreciate your approach is that MS is MS without differentiating. It reminds me of a physician’s opinion that “classic” trigeminal neuralgia and “atypical” TN are TN. End of. This such heartening news for younger pwMS. I like the adverse effects profile so far. Thank you as always for keeping us informed. Great news! 🌷
Prof. G, Any thoughts on whether this monoclonal antibody can theoretically be effective in treating SPMS or, daresay, subsequently reverse damage? I recognize it is early and speculative....that is why I included the word "theoretically" in the question. Thank you for all you do.
Thanks as ever prof G for taking the time to inform and educate pwMS. And additional thanks to Simon Brown for all the explanations. News like this brings much needed hope to this parent of a child with MS.
Prof G, is there any value in these existing therapeutics for CD04L?
An alternative antiplatelet agent that has been shown to reduce the activation-induced release of sCD04L from platelets is dipyridamole the; major way in which it inhibits platelets is via phosphodiesterase (PDE) inhibition.
Furthermore, ibudilast, an alternative PDE inhibitor, attenuated Tat-induced inflammatory responses in a murine microglial cell line [73] and it has been shown to control the release of sCD40L from platelets.
Source: 2013 Targeting platelet-derived soluble CD40 ligand: a new treatment strategy for HIV-associated neuroinflammation?
Lupus -> Frontal lobe lesions -> "Schizophrenia" / other similar conditions...
Treated with rituximab (same mechanism as Ocrevus).
Potentially the same cause, EBV? We know they're testing frex on lupus as well. This work could have implications far beyond MS in some very serious and seemingly intractable mental health cases...
What would be the risks/possibility of pwMS having anti virals outside a trial? As pointed out by others before patients with AIDs and Covid saw improvement in their MS symptoms while on anti virals.
Having recently joined a 2 year Ph3 BTKi trial, do the anti-CD40L revelations mean I've just boarded the wrong bus?
Facetious comment as an equivalent Frexalimab trial won't be ready in the lifetime of the trial I've joined and I'm hoping it makes a positive impact on my progression. However, it's tough on the pharmas if they are part-way to market on meds that could be virtually obsolete by the time they can release them to market.
May 31, 2023·edited May 31, 2023Liked by Gavin Giovannoni
Doesn't seem to deplete lymphocytes so we'd have almost fully-functional immune systems (apart from the broken bits which would be turned off by frex).
I appreciate that "MS is all one disease" but there is PIRA and progression in patients with full CD20-induced B cell depletion so there has to be SOMETHING making that happen. T cells with some kind of memory triggered by CD40 to CD40L (CD154) on the T cells maybe?
We know that antibodies are blocked by the blood brain barrier (BBB), whereas B & T cells, 1000x bigger than antibodies, are allowed across.
So presumably as this blocks CD40L rather than inducing apoptosis (killing the cell completely)...
CD40/L-blocked B & T cells are allowed in, across the BBB...
and then don't attack myelin as they've forgotten how to...
eventually allowing progression to stop...
and maybe even reverse a little bit?
Would there be attendant blood tests to see when EBV has been eradicated completely? Presumably at that point frex could be reduced to see if MS reactivates. And if it doesn't then the MS has, in effect, been (I hesitate to use the C word) rendered dormant?
I'm 56. I'll be dead before anything comes to market to help me lol. Good news for those coming up behind though and those who haven't yet been diagnosed.
Please can I have some Frexalimab. I have been reading about MS research since I was diagnosed age 30 when my son was 2. He is now 38 and I have just filled in the form to claim my state pension. Just give me the drugs.....PX
Thank you Prof G.
You are one of the few leaders, leading the courageous fight against the MonSter, keep up the pressure and theorizing.
I Inform anyone who will listen to find you.
My MS Dr in Texas discuss's you quite often now, I've discussed your theories for years.
I hope we get to the remission promise land, too many of us are suffering, especially the younger MS patients need a bone.
I think my comment got dropped when I edited one? My brain is smouldering away! In any event, the gist was I am far too old for this, but I’m extremely excited by this research. I also appreciate your approach is that MS is MS without differentiating. It reminds me of a physician’s opinion that “classic” trigeminal neuralgia and “atypical” TN are TN. End of. This such heartening news for younger pwMS. I like the adverse effects profile so far. Thank you as always for keeping us informed. Great news! 🌷
Prof. G, Any thoughts on whether this monoclonal antibody can theoretically be effective in treating SPMS or, daresay, subsequently reverse damage? I recognize it is early and speculative....that is why I included the word "theoretically" in the question. Thank you for all you do.
Thanks as ever prof G for taking the time to inform and educate pwMS. And additional thanks to Simon Brown for all the explanations. News like this brings much needed hope to this parent of a child with MS.
This seems to be aimed at RMS, do you think it will potentially help with smouldering MS?
I would also be interested to know if there’s any potential for SPMS? And does this drug immunosuppress and hence expose the patient to PML? Thankyou!
Prof G, is there any value in these existing therapeutics for CD04L?
An alternative antiplatelet agent that has been shown to reduce the activation-induced release of sCD04L from platelets is dipyridamole the; major way in which it inhibits platelets is via phosphodiesterase (PDE) inhibition.
Furthermore, ibudilast, an alternative PDE inhibitor, attenuated Tat-induced inflammatory responses in a murine microglial cell line [73] and it has been shown to control the release of sCD40L from platelets.
Source: 2013 Targeting platelet-derived soluble CD40 ligand: a new treatment strategy for HIV-associated neuroinflammation?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906985/
2019 Dipyridamole as a new drug to prevent Epstein-Barr virus reactivation
https://www.sciencedirect.com/science/article/pii/S0166354219303304
https://www.washingtonpost.com/wellness/2023/06/01/schizophrenia-autoimmune-lupus-psychiatry/
Lupus -> Frontal lobe lesions -> "Schizophrenia" / other similar conditions...
Treated with rituximab (same mechanism as Ocrevus).
Potentially the same cause, EBV? We know they're testing frex on lupus as well. This work could have implications far beyond MS in some very serious and seemingly intractable mental health cases...
What would be the risks/possibility of pwMS having anti virals outside a trial? As pointed out by others before patients with AIDs and Covid saw improvement in their MS symptoms while on anti virals.
Having recently joined a 2 year Ph3 BTKi trial, do the anti-CD40L revelations mean I've just boarded the wrong bus?
Facetious comment as an equivalent Frexalimab trial won't be ready in the lifetime of the trial I've joined and I'm hoping it makes a positive impact on my progression. However, it's tough on the pharmas if they are part-way to market on meds that could be virtually obsolete by the time they can release them to market.
I'm excited to read such news,however I am wondering if this includes All types of MS ..this wasn't made clear.
Doesn't seem to deplete lymphocytes so we'd have almost fully-functional immune systems (apart from the broken bits which would be turned off by frex).
I appreciate that "MS is all one disease" but there is PIRA and progression in patients with full CD20-induced B cell depletion so there has to be SOMETHING making that happen. T cells with some kind of memory triggered by CD40 to CD40L (CD154) on the T cells maybe?
We know that antibodies are blocked by the blood brain barrier (BBB), whereas B & T cells, 1000x bigger than antibodies, are allowed across.
So presumably as this blocks CD40L rather than inducing apoptosis (killing the cell completely)...
CD40/L-blocked B & T cells are allowed in, across the BBB...
and then don't attack myelin as they've forgotten how to...
eventually allowing progression to stop...
and maybe even reverse a little bit?
Would there be attendant blood tests to see when EBV has been eradicated completely? Presumably at that point frex could be reduced to see if MS reactivates. And if it doesn't then the MS has, in effect, been (I hesitate to use the C word) rendered dormant?
Wow great stuff doc!!!!
A question though: I never had Gad enh. Lesions. Does this mean cd40, cd40l does not apply to me? Rob
Do you know if there any plans for trials in primary progressive MS? Thanks