Disappointing. I wonder if this is true for the US NIH, who have all of that RECOVER money that they keep unwisely spending...
Open Norway: Plasma cell aimed treatment with daratumumab in ME/CFS - Haukeland University Hospital
- Thread starter Kalliope
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- cd38 daratumumab norway
Jonathan Edwards
Senior Member (Voting Rights)
That is NIHR which is probably a dead loss here. NIH is more relevant. They fund work in other countries - like Jackie Cliff's work (and some stuff in Wuhan!).
Sasha
Senior Member (Voting Rights)
That's good news! How can the dara trial be brought to their attention? Or the NIH to Haukeland's attention? The UK should definitely be supporting crucial trials, wherever they're happening.
NIH do not proactively approach researchers — they must apply for funding. So they need to contact them. Vicki Whitmore is very responsive and will set up a call w them. they should also apply to the EU for next year. (The horizon 25 deadline was 3 days ago)
EU Funding & Tenders Portal
The Funding and Tenders Portal is the single entry point (the Single Electronic Data Interchange Area) for applicants, contractors and experts in funding programmes and procurements managed by the European Commission.
BrightCandle
Senior Member (Voting Rights)
As we heard in the roundtable yesterday the fastest the NIH et el can do n the USA is about 18 months. Doubt any of this would resolve quicker with the EU than 12 months. But I also doubt the patient community has 850k to fund this project its just too much for one independent project. Their better bet is probably the charities Solve ME, Action for ME, ME Research etc, that should be doable faster.
NIH do not proactively approach researchers — they must apply for funding. So they need to contact them. Vicki Whitmore is very responsive and will set up a call w them. they should also apply to the EU for next year. (The horizon 25 deadline was 3 days ago)
EU Funding & Tenders Portal
The Funding and Tenders Portal is the single entry point (the Single Electronic Data Interchange Area) for applicants, contractors and experts in funding programmes and procurements managed by the European Commission.ec.europa.eu
You seem quite knowledgeable about this stuff - would you be willing to email F&M about seeking funding from the NIH, EU and Khosla? I believe I found a contact email somewhere online.
I think its not unlikely they applied for Horizon this year but who knows. They may have tried NIH and Khosla too but we won't know unless we ask.
Or perhaps @Jonathan Edwards you could get in touch with Fluge about this?
Sure, I can do that. I just found two emails for Fluge, so will try to get in touch.
Thank you! Really appreciated.
Jonathan Edwards
Senior Member (Voting Rights)
I am coming to think that dara tumumab does make sense as the one repurposed drug that has a clear, if speculative, rationale for ME/CFS and Longer Long Covid.
The research we think make some sort of sense, including DecodeME findings all seems to point to some persistent 'trap' that cell signalling gets stuck in. That might involve cytokines, antibodies, expansions of cell subpopulations, metabolic pathway diversions or all of them. It is likely to involve at least some of B cells, T cells, macrophages, dendritic cells and stromal cells like fibroblasts and maybe even adipocytes.
The repurposing strategies that might break a cycle and get things out of the trap include rituximab, which has failed, blockade of TNF or other parts of related pathways like NFkB with etanercept etc. which has failed. JAK kinase blockade seems to be under way but I have a suspicion we would already know if it did something striking.
Daratumumab might seem a bit left field but if you want a drug that throws one or more spanners in the works (targeting antibody pools and CD38 itself) in a novel way that might stop adaptive and innate immune cells getting each other confused it ticks a good number of boxes.
Moreover, both the NK data on the responder/non-responder split and the shapes of the response (and non-response) tracks make me think there is at least a 50% chance that this is a real effect. That is a lot higher than I would have put things after phase 2 rituximab. And it is way higher than I would put anything else.
It is worth investing $10-20M, I would say, in the context of money being thrown in all sorts of other directions.
The research we think make some sort of sense, including DecodeME findings all seems to point to some persistent 'trap' that cell signalling gets stuck in. That might involve cytokines, antibodies, expansions of cell subpopulations, metabolic pathway diversions or all of them. It is likely to involve at least some of B cells, T cells, macrophages, dendritic cells and stromal cells like fibroblasts and maybe even adipocytes.
The repurposing strategies that might break a cycle and get things out of the trap include rituximab, which has failed, blockade of TNF or other parts of related pathways like NFkB with etanercept etc. which has failed. JAK kinase blockade seems to be under way but I have a suspicion we would already know if it did something striking.
Daratumumab might seem a bit left field but if you want a drug that throws one or more spanners in the works (targeting antibody pools and CD38 itself) in a novel way that might stop adaptive and innate immune cells getting each other confused it ticks a good number of boxes.
Moreover, both the NK data on the responder/non-responder split and the shapes of the response (and non-response) tracks make me think there is at least a 50% chance that this is a real effect. That is a lot higher than I would have put things after phase 2 rituximab. And it is way higher than I would put anything else.
It is worth investing $10-20M, I would say, in the context of money being thrown in all sorts of other directions.
Utsikt
Senior Member (Voting Rights)
what would you expect the time profile to look like if JAK kinase blockade works? Are we sure the trials are set up to detect any effects if they are there? I think I remember you talking about other drugs flunking in trials for many years because the people trialing them didn’t know how to use them properly.
OrganicChilli
Senior Member (Voting Rights)
I think I've asked this question before, but would Isatuximab be a good alternative for dara non-responders? Assuming that NK cell count is critical and isatuximab doesn't depend on it as much.
I’ve had a very smart person mention that they thought isa would be better than dara. I asked one of the Haukeland people why they chose dara over isa and she mentioned that dara was the older drug and therefore had a better (longer) safety record.
Having said that, I think you are still going to need NK cells for Isa.
With low NK cells maybe the option is the protesome inhibitors like Bort or ixazomib.
OrganicChilli
Senior Member (Voting Rights)
What about CD38 CAR-T cell therapy? Hypothetically speaking.
A bispecific CAR-T cell therapy targeting BCMA and CD38 in relapsed or refractory multiple myeloma - Journal of Hematology & Oncology
Background BCMA-specific chimeric antigen receptor-T cells (CAR-Ts) have exhibited remarkable efficacy in refractory or relapsed multiple myeloma (RRMM); however, primary resistance and relapse exist with single-target immunotherapy. Bispecific CARs are proposed to mitigate these limitations...
jhoonline.biomedcentral.com
https://pubmed.ncbi.nlm.nih.gov/37039305/
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Sasha
Senior Member (Voting Rights)
I haven't read all this thread so I hope this isn't the wrong thread or that I'm repeating a question but I was just looking at this account of the dara pilot and I'm struck by the difference (p.5) between baseline characteristsics of improvers and non-improvers in relation to length of illness and severity. Improvers seem to have had ME/CFS for far longer and to have had more severe illness. What do we make of that?
Kitty
Senior Member (Voting Rights)
Say the Norwegian team got their £2 million for this trial and it showed a response that does look convincing. Do you think there'd be a reasonable chance of getting a UK replication study?
I know it doesn't matter where studies take place from the point of view of the science, but I'm thinking selfishly about the problems UK ME/CFS patients face with the rehab machine that's currently gearing up. Particularly after @Trish's post about cranial assaults on brick walls.
Presumably such a trial would have to be run in partnership with a couple of hospitals that have the expertise to administer the drug and do the monitoring. Strikes me that would be a good way to generate talk among clinicians—probably sceptical until it reported, but at least they'd be discussing a robust trial of an actual treatment. One that shows trials are possible and worthwhile in ME/CFS and has the potential to raise the question "Well, what about X or Y?" if the results were disappointing.
ETA: Amuses me no end to think that if they weren't disappointing, we'd all be planning our rehab.
ryanc97
Senior Member (Voting Rights)
This is not true, the non responders were 2 severe 2 mod and responders were 6 moderate.
It just so happens the 2 severe patients also has the lowest NK cells.
The improvers mean illness duration is skewed up by one responder who has had it for 35 years that went into remission, Fluge mentions this in his video, but does not state who is the patient number.
Likewise because for IGG4 we only have means it is possible the mean is skewed up by one person with super high IGG4
Sadly they do not release the individual data or if someone has it pls share
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ryanc97
Senior Member (Voting Rights)
This MM doc says no diff in his experience from treating with Isa vs Dara (see picture)
ChatGPT says Isa is a better CD38 blocker and depletes NK cells less so it would seem in theory it is even better than Daratumumab regardless of which theory (LLPC vs CD38).
I might be able to see a blood cancer doc that my immunologist is referring to, I will ask him on these things. Mainly to see if Teclistamab is possible if I can’t get my NK cells up enough for Dara
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Sasha
Senior Member (Voting Rights)
Google's AI says this:
Google AI said:
I don't understand any of that! Can anyone explain when it might come off-patent in the UK and Europe (which would make trials cheaper here, presumably?)?