Just a test

You in bold (me responding to dachopper's post 69258225 dated 10 Aug 23 - reposting (if second attempt fails) to test forum because some block on the post handling is preventing posting to the MSB forum at present in the means I am trying to use).

What happens if a patient who has a MAP score > 0.29 recieves an INF Gamma increasing MSC, and then survives?

--- Respectfully, (and yes, I did see your post after this one with the graphics and I do know that you've faithfully sourced some MSB material (but I don't think its relevant to your question) (and Ihad seen that research before), your question seems tangled up to me.

Are you suggesting that you know of even a single circumstance in real life where "a patient who had a MAP score > 0.29 received an INF-gamma increasing MSC and then survived"?

Because I don't think that would have been investigated or done because I think that is not what the MAP score is about - its a surrogate biomarker for survival (its in that sense (as a surrogate biomarker for survival - and certain not as a potency assay) that its authors and patent holders claim for it to have been validated) - its not a potency assay at all, let alone a validated (in someone's opinion or through demonstated methodical science in a peer reviewed journal) potency assay.

Unless things have changed in the last 18months to 2 years the FDA allows certain biomarkers to be registered with it. But they don't have to be. MAP isn't or wasn't last I looked. Validation of a biomarker can be done on the strength of the science demonstrated in scientific papers - and it is in that sense not the registered with the FDA sense that the MAP score stuff is said to have been validated - (and I largely agree - I read a bunch of the related papers - it looks to be pretty validated to me - but its got limits - and it has nothing to do with MSBs two part matrix approach to potency assay validation.

I stress this important point to you -- A validate surrogate biomarker for survival (the MAP score) is a different thing entirely to a validated potency assay (though both have the word validated in them and both involve things that can be measured in blood samples). I think you get that - but your question suggest maybe you don't completely. There is no relationship I can think of off hand between ST and reg3a blood levels in blood (which is what the MAP score is working with) and TNFR1 and IL2Ralpha (CD25) which is what the potency assay matrix approach (as disclosed by MSB) are concerned with. Two tools for two different purposes.

If you agree with and understood already that they were two different things/tools for two different purposes than your question to me looks very strangely constructed - like it is you not me that is constructing a strange hypothetical.

When MSB wanted to show a relationship between their potency assay component IL2Ralpha in vivo and in vitro - they did it with blood samples taken from some eleven or so patients in the GVHD001 trial for which they had information on both the single lot amounts of IL2ralpha amounts and the before and after (specifically I think it was 28 days after) blood readings in the patients of that same molecule (ie CD25 - so not ST or reg3alpha) as measured on FACS (florescent activated cell sorting - sometimes called flow cytometry) readings. This is a slide I've referred to on several occasions previously it has an r2 of 0.35 only from memory and as shown by MSB doesn't scale the horizontal axis correctly.

Here it is - (this slide cc-32 has some of my comments on it - not sure if I've posted it before with my comments or not).

Currently there is no in Vivo evidence that a cell that does or even does not decrease Inf Gamma has any effect on survival - so you are postulating that an unproven hypothetical would cause concern over what is now becoming proven in Vivo survival data?
One is theoretical, the other is practical data.

That statement of yours that I've highlighted in yellow is one heck of big statement by you! And you include it as part of a longer sentence that also includes a characterisation of my position (that I'm postulating an unproven hypothesis) which you do at least have the courtesy to express as a question.

Have you googled to check my claim that INF-gamma was once called macrophage activating factor ? - I could be wrong remember, (***) but if I'm right there would have been some process by which it got that name. And it easily could have been by doing some work with INF-gamma and macrophages in vitro (meaning essentially in a lab dish as opposed to in vivo) but if something happens in vitro (say INF gamma has an observable effect on a macrophage) then that would be SOME evidence that it likely could also happen in vivo. Stuff that happens at the cytokine level between cytokines and specific types of cells in vitro is also likely to happen in vivo -because molecules are molecules.

(***) I just jumped onto another computer - because I post to Hotcoper in Tor browser and don't want all the HC advertisers tracking me about - I have to use another computer to cross check some facts - "when i put "macrophage activating factor" and "interferon gamma" together on my laptop I go straight to a 19 June 2018 nature reviews immunology article. "IFNy: signalling, epigentics and roles in immunity metabolism, disease and cancer immunotherapy"

One can reduce IL2R alpha by around 80%, the other in contrast cause minor increases and decreases to INF Gamma < 30%.

How can you possibly know that swings of up to 30% INF gamma in an in vitro scenario (that is when one lot of MSB MSCs is added versus another lot or versus it not being added at all) is minor when that same product is put into a patient?

Look I apoligse for the poor structuring and repetitiveness of some of my posts but previous experience has made me doubt the wisdom of spending a lot of time post polishing to make the post read easier. That both previous experience with you - who I have not found to be particularly appreciate of the efforts I've made with you and previous experience with the forum - I've previously gone to some efforts to post science specifics and have someone like pledge repost exactly what I posted to someone like gav--66 as if it was an example of pulling the wings of flys - when had pledge only taken the time to try to understand it he might have learned some useful cell biology that directly related to the likelihood of MSB getting a BLA. This has happened to me a lot and I often feel I have not invested my time and effort in the right places and with the right people on the basis of how they have responded when I thought I was generous with them.

Originally posted by JB1975: ↑

@gerzensee wrote (post 69173929) : “sadlyfor the kids” No.I reject the premise in that entirely.

Interms of the greatest good for the greatest number more kids in theaggregate and more families of kids will be better off for the FDAreaching a sound scientific and statistical conclusion.

MSBand shareholders can now choose to learn. Or not. It ain't lookinggood for learning going on the tick counts. Looking at the tickcounts on posts after the decision - see for instance OPs post andthe GA ticks in the thread with a heading about the FDA beingcorrupt.

Icorrectly as it turned out called the result and said insufficientevidence because that was what my own honest analysis and homework(and I did a lot of homework) brought me to conclude.

Itis completely untenable to have the developers of medicine proceed ona honors system - whereby on their honor - they'd be left to improvetheir products and to bring their prices down so as to make effectivemedicines affordable.

Thebelief shareholders have had formerly, and going by the content ofthe posts on this forum since the result, s not based on anunderstanding of the underlying science and technology.

But the diseases are based on scientifically real andunderstandable phenomenon. Too much time is spent reading between thelines of announcements and not reading what is actually on the lines.

Factsare stubborn things. They don't give a fig for tick counts. Butanyone can learn them its just most choose not to. Most don't do thehomework. Most are effectively free carried on the backs of thosethat do. Some will turn up to get medical treatment and be a drain onthe system that they have spent enormous amounts of time underminingbecause they couldn't be objective and worse they attacked those whowere objective - and its in the trying to be objective thatdiscoveries are made and knowledge is acquired - knowledge like howdisease works and how to work on the mechanisms of action.

Prettymuch anyone can learn some cell biology and some science - it isn'teasy but (nor is it hard) and it doesn't hold itself aloof.

Thisforum could have been used, it was always a matter of choice, toexchange information and for mutual learning.

Eachperson posting can choose the sort of correspondent they want to be.But I've no interest in corresponding with people who choose nastyall the time. And I don't have the time to correct all themisrepresentations.

FranklyI'm seeing a lot of something very like karma happening.

Inmy opinion, human lives are lost earlier than they need to be all thetime because we are connected to each other in networks, communities,societies, and the bad that some of us do effects the networks,communities and societies in which we live. In my opinion the cureswe have for diseases and the standards of living we enjoy (we couldhave better medicines and cheaper medicines for instance) aresubstantially constrained by bad behavior. Too many of us feed thedark wolf - and that has consequences.

Isee people consoling themselves that might be better off notconsoling themselves for a while but rather shutting up and thinkingand reading to see where they went wrong in their thinkingpreviously- because in my opinion many are bigoting (makingsubjective prejudgements including on others and on the evidence -reading between the lines my butt) themselves to premature death.

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@dachopper - if you want feel - if you feel others will get something from seeing this or continuing this discussion in the forum I tried to post it feel free to repost it - I'm just too impatient at present to buggerize around with hotcoppers post button processing on the MSB forum.