MSB mesoblast limited
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@LeftYahooThank you so much for taking the time to respond and...

  1. stanjupiter
    965 Posts.
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    09/06/25
    14:20
    Post #: 79366597
    @LeftYahoo

    Thank you so much for taking the time to respond and the very helpful information!


    Yes, I was asking why it couldn’t be a two-way street. You put that in a nutshell. Just one point I wasn’t quite clear on. Are you saying AA for Rex for class 2,3 would be less likely than for LVAD because there’s already something (SGL2 inhibitors) for that category (class 2,3) to reduce the risk of hospitalisations for cardiac events which Rex achieved showing MACE reductions? (I so agree I should have been precise. I looked up decompensated HF a while ago but it wasn’t explained as clearly as you have.)



    The reason I mentioned statins, beta blockers was to say that despite all these medications there’s still progression. I think the phase 3 in Vericiguat was before Entresto but 17% of the cohort died of cardiac causes in the very short trial period. I found online that Abbott has seen an uptick in LVAD sales. In 2024 they had problems with some devices that had to be recalled. Surely the best strategy is to try to stop progression to end stage?



    This is just my layperson’s view but I thought that endothelial dysfunction can lead to inflammation and that correcting ED (evidence of repair of vessels that were friable and leaky) was a form of regeneration. Most importantly, it gets to the root cause, rather than addressing symptoms. The causes of HF are complex tho and there’s a need for a therapy that can address this - cells that are intelligent machines which can communicate with the host’s own intelligent machines. (I recall from Dr Perin’s talk he said everyone is different and we don’t fully understand the complex interaction of the innate and adaptive immune systems.)


    You mentioned Prof Caplan. I watched his lecture on YT. I recall he talked about MSCs’ action on endotoxins. Geoff Pain is an Australian scientist I subscribe to. He says he met Aseem Malhotra on his world tour and that he and VP know about endotoxin-induced heart disease:




    I’ve yet to go over this paper in detail but I homed in on M1 and M2 macrophages and one basic scientific thing I learned about endotoxin-induced ARDS was that MSCs switch from M1 (inflammatory) to M2 (anti inflammatory).


    Further Evidence From Ryoncil and an Obvious Additional Application?


    Further, MSB’s report on the ARDS trial states severe Covid was similar to Hemophagocytic Lymphohistiocytosis (HLH). HLH is also called macrophage activation syndrome and very common in juvenile idiopathic arthritis. Perhaps this is one condition SI might have had in mind when he referred to the potential application for Ryoncil for other childhood inflammatory diseases?


    In September last year, I emailed MSB for the attention of Dr Rose and suggested they contact Vinay Prasad who, in his capacity as a hematologist, may have been seeing an uptick in cases of secondary HLH (It’s in the database, as is Hypoplastic Left Heart Syndrome, on the Nord website for rare diseases for which VP recently gave the keynote address.)


    In a previous post, I referred to Dr. Eric Strong (Strong Medicine on YT) who says two tests are important to diagnose sHLH but not often done: Check for lower NK cell activity and elevated IL2 receptor (aka CD25). Cattaneo et al. (2016), who report appalling survival in HLH, say these tests were not available for most patients. Ruxolitinib is being used off-label for sHLH!


    Both VP and PK have written about original antigenic sin, which can lead to a cytokine storm. (My own theory is that what we’re told is Ebola is actually sHLH and I have an idea why. )


    Back to the heart…


    Another reason I mentioned statins, beta blockers etc. is that I was putting my patient hat on, specifically the POV of the young man who commented on VP’s YT presentation. I was saying: OK Vinay, you’ve laid into everything but what are you offering?


    VP wasn’t long out of med school when he took on Milton Packer (in a collegiate way). IN 2016 MP wrote an article lamenting the state of trials in HF (The letters on Vericiguat’s report in the NEJM were cynical):


    “We will always find a sliver of hope in a totally neutral trial that has failed to meet any of its expectations, and we will always find something lacking in a trial with overwhelmingly robust results. There is no trial that is too negative, and there is no trial that is good enough. Regrettably, if you ask a clinical trialist for the solution to a problem, the answer will always be—a new clinical trial”.


    We’re not talking about a tablet and Dream HF took ages to enrol. There’s even more urgency now, particularly with younger people. Rushing drugs on the market does a disservice to patients but so does failure to act.



    Again, I welcome corrections if you or anyone has the time. Thank you again for taking the time to comment and for your good wishes for us on the King’s birthday. I hope it’s sunny and warm where you are!


    All IMO

    MSB Price at posting: $1.76 Sentiment: Buy Disclosure: Held
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