New potential therapeutic target for MF

[Paul123456]

Possible new breakthrough re MF. Early days but one to watch....

nature.com/articles/s41467-...

“To summarize, using two murine models of myelofibrosis, we show that a specific HSP27 inhibitor, OGX-427, limits the progression of myelofibrosis by (i) reducing both spleen weight and size, (ii) decreasing myeloid proliferation in the spleen and bone marrow, and by reducing megakaryocytic expansion, (iii) decreasing reticulin fibrosis and (iv) normalizing the platelet and white blood counts. We also show, for the first time, that HSP27 may chaperone JAK2/STAT5, a central signalling pathway activated in MF-associated MPN, and also in other kinds of diseases72, 73. Altogether, our results support a key role for HSP27 in the pathophysiology of MF and highlight a potential interest of HSP27 inhibitors as a complementary approach for MF-associated MPN treatment.”

[Norman45]

Wish I could understand all the technicalities but this sounds like very good news on the horizon for us MF sufferers.

[eire]

Thanks for sharing Paul. Agree with Norman the technicalities are mind blowing but nevertheless more hope!!!! Newly diagnosed MF patients have a lot more therapies and the way research is going a cure could be there in the near future. Who knows!!!

[Paul123456 in reply to eire]

I’m afraid only about 10% of what works on mice transfers to successful human trials but this one looks particularly encouraging. IMO the quicker the experts understand the reasons for, and the ways MF evolves, the quicker the ‘cure’. This indicates they are making good progress.

The other read across is that there is lots going on behind the scene and even odds of 1:10 are good if enough rolls of the dice!

[beetle]

Thanks for posting this Paul. You really have your finger on the pulse don’t you! A great contributor to our group 😊

This looks as though it might be another breakthrough and we certainly need one but many a theory put forward from a mouse model falls apart in humans unfortunately. It’s definitely one to keep an eye on and it is reassuring that there is continued research into our orphan diseases. I do wonder how they give mice MF in the first place? They must somehow give them one or more of the mutations that we suffer from. It’s all a bit beyond my ancient biology studies. They had only just invented the electromagnetic microscope when I left school and look how far we have come since then

It really should give hope to anyone newly diagnosed and the old prognostic schematic might soon become redundant

Thanks again for all your fascinating and informative posts. Keep them coming!

Very best wishes, Jan

[Paul123456 in reply to beetle]

Thanks Jan. I’m so sorry for those of you who are facing the dilemma of SCT timing. I know you see Prof Harrison so at least you can very much draw on her wisdom. I know you were getting Myeloid Gene tested, have you had the results?

I got mine, was TET2 +ve which possibly means Peginteferon won’t work quite so effectively.

Best wishes Paul

[beetle]

Hi Paul, my testing thankfully came back Jak2 +ve which I already knew with no new mutations- thank goodness. I have stopped agonising over the SCT and decided against it from strong recommendations when I was in Scotland. My haemo said the decision over SCT was a bit like standing on a cliff edge and deciding to jump in the hope that the parachute would open. i.e. successful transplant or wait until a later date when the wind will blow you off without the parachute! Using that analogy I was advised that if I jumped I would already have a faulty parachute. I am now standing as far away from the cliff edge as possible with every possible windbreak around me! Who knows, they might discover a lift to take me safely off the cliff. I live in hope 😊

Thanks again for your posts. Best wishes, Jan

[Paul123456 in reply to beetle]

Relieved you have no nasty mutations, that should buy you significantly more time for someone to build a lift or even invent a better parachute. We are obviously all hoping for a new golden bullet drug that will slow or stop MF but there is also research ongoing re SCT, both into avoiding/reducing the risks of chemo/radiation but also mitigating GVHD.

My regular Hem has retired and been replaced by someone who is an SCT expert. I will be seeing him next month for a check up, will ask what’s in the pipeline and report back.

Best Paul

[beetle in reply to Paul123456]

I look forward to hearing what he has to say about any developments in SCT. There seem to be SO many going through it at the moment in USA