INF+ ATO Study, "A knockout combination for MPN stem cells"

[EPguy]

Some have likely seen this study. I looked into it some more today and realize it's a neat pre-clinical result. This is just FYI right now but it's an example of potential good things to come.

(I just noticed Manouche posted on this last year, anyway maybe some new details here)

"JAK2V617F myeloproliferative neoplasm eradication by a novel interferon/arsenic therapy involves PML" and "A knockout combination for MPN stem cells"

ncbi.nlm.nih.gov/pmc/articl...

ncbi.nlm.nih.gov/pmc/articl...

The image shows two charts I selected that I could fairly understand. The tan colored bars are the combination of INF with arsenic trioxide, a drug used for a type of leukemia. It's clear that this combo is very effective.

They use mice that are given MF or PV via marrow transplant, (Knock-in mice) a common method I've seen in studies.

Fig. d is measurements of Jak 2 mutants. I don't understand the details but the general improvement over others including INF is impressive.

Fig. e is what happened to healthy mice that got BM transplant from treated mice. The marrow from ATO+INF mice did not harm the healthy mice, they report 100% survival, while marrow from INF and un-treated mice made trouble for the healthy ones, see quote below.

From the 2nd reference

<<Functionally, MPN stem cell populations were unable to transplant MPN into irradiated secondary recipients, an assay considered a gold standard of leukemia stem cell function. Additionally, after IFNα+ATO treatment was withdrawn, primary mice were monitored for the reemergence of disease. In >50% of the IFNα+ATO combination–treated mice, the MPN did not recur after treatment was stopped, demonstrating long-term treatment-free remission and potentially a cure of the MPN.>>

My take is this therapy could make INF treatment work way faster and better. ATO is currently used as an IV but there are some new pill versions the authors note that would make this an outpatient therapy. One such new ATO pill is "SY-2101"

I hope there are follow up studies getting started.

[EmeraldA]

I had forgotten about this study. It looks promising and I really hope that they follow up on this! Thanks for posting! B

[EPguy in reply to EmeraldA]

The maker of Ropeg INF (P1101) , PharmaEssentia, has in their new products pipeline a "Next Generations of P1101". It could be they are planning to test this new combo using ATO. Just a guess.

[Norma1831]

Thank you for your posts on such promising research into a cure for ET. Good to know this is underway and have the science summarised so well for non scientific but interested readers on this forum.

[Wyebird]

Facinating, it would be lovely if Maz could arrange someone to speak on this in a future forum

[EPguy in reply to Wyebird]

That would be neat to have a speaker on it. As in the post:

healthunlocked.com/mpnvoice...

ATO-INF <<These results have led to the planning of IFN and arsenic based clinical trial approaches for MPN patients.>>

Maybe Maz can find out more about any trial.