This looks a really promising new treatment

[Paul123456]

I have posted this link before but worth repeating for new members of this Board.

RG7388 is an existing drug used in Acute Leukaemia, hence has a track record.

My very rough and amateurish synopsis:

We all have a p53 gene which effectively fights cancer.

Some/all of us have another gene called MDM2 which is stimulated by our JAK2 mutation into suppressing the good work being done by p53.

RG7388 kicks MDM2’s ass!

This link explains it must better

cancernetwork.com/ash-stree...

We know that Peg/Inf can reduce the % JAK Allele Burden which presumably reduces the ability of MDM2 to downgrade p53. However we also know that something else going on, that reducing Allele Burden not enough.

RG7388 looks a very useful new bullet and can be used with good effect in combination with Peg.

Is this the Silver bullet we are all hoping for? Probably not but if it wipes out one of our most dangerous mutations, it’s great news. Phase 2 trials about to begin.

[JohnSC]

Hi Paul,

Thanks for posting the information and link, it all sounds very promising and certainly a trial to follow.

John

[MPort]

Thanks Paul. Your explanation is very helpful. I will print out this info and keep it in my blood count record file. It will be interesting to see how it goes in next trial. In a few years it might come into our treatment options.

Mairead

[Paul123456 in reply to MPort]

Since it is already in use, in much higher dosages, for Acute Leukemia l’d hope a successful Phase 2 trial would be followed by rapid roll out. IMO our best hopes at the moment, Ropeginterferon/Pegasys and Ruxo, are effective but rather blunt instruments that don’t work for everyone. Plus some people still seem to ‘progress’ more aggressively than others. If the reason is that their ability to fight their MPN has been diminished by high MDM2 and RG7388 resolves this, then would be a major breakthrough. The logic behind the Presentation is compelling so fingers crossed!

IMO, since JAK2 was discovered, the research has focused a bit too much on lowering Allele Burden (the % of mutated JAK) whereas there is now greater interest in the other factors/mutations. It has become clear that simply lowering Allele Burden is not enough.

I view our condition as similar to a slowly sinking ship with multiple leaking holes. Some of us have more leaks (mutations) than others. Inf/Peg plugs some holes, RG7388 could plug a major hole for some/all people. Maybe for many people this combination will be sufficient to pretty much arrest progression. For others, it could slow progression (sinking), allowing researchers more time to identify and plug the other mutations.

[Brook04]

Wow ill be asking my husbands heamatologist about this

[tessa46]

Thanks Paul, this looks really interesting. I have ET and I have been on Interferon (Pegasys) for nearly 6 months and my haematologist has said to me that when it is a year, they will do another JAK2 test to determine whether the allele burden has reduced. So I will discuss this research with my haematologist at my appointment in April. Thanks for posting the link.

[MPort]

Hi Paul

I have been tied up so late reply. What you write and the analogy you use is helpful but also depressing. However it makes sense and I can understand complicated ideas easier with 'leaking holes and sinking ships'. I am entering my 13th year with PV and while Jak2 positive it's so long since I had a bone marrow or any other background checks I have no info on other missing parts or burdens. So I have to live in hope. But with info from people like you who understand it I hope to keep up and be able to ask for other medication if and when I need it. Since I got PV I have discovered the benefits of being well informed and being my own advocate.

Many thanks again.

Mairead