NAC inhibits Jak2 thrombosis in MPN Study

[gvibes]

Just came upon this. Thought this might be interesting to some

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

[EPguy]

This seems to be a fresh look at the familiar mouse NAC studies.

-Top conclusion is NAC reduces thrombosis as well as aspirin but has added benefit for the mouse of longer life, while aspirin did not affect MPN life span. Extra life was from less thrombosis.

-A stand out note is re PLT effects. They found, as in a recent post, that PLT activation had no relation to thrombosis. More support for the idea that modestly high PLT is not a thromb risk (here being in mice)

-They made their mice to 100% Jak2 AB. This seems not realistic for most MPN. They say this might be a reason they didn't see some other benefits seen in earlier mouse studies. I recall some showed reduction in the clone, it might require some good Jak2 remaining (<100%AB) to get there.

-Dr Fleischman was involved and notes the NAC trial that is happening right now.

--

<<These data suggest that NAC extends the lifespan of mice with MPN through a mechanism independent of cytoreduction>>

<<Because hematopoiesis in our model is made up entirely of JAK2V617F cells, this could explain why we did not see the same impact on blood counts or spleen weight as Marty et al>>

<,NAC was as effective as aspirin at reducing an induced thrombus in WT mice, aspirin did not improve survival of JAK2V617F knockin mice, suggesting that NAC has additional benefits in MPN that are distinct from aspirin>>

<,Our data suggest that classical platelet activation is not the primary mechanism of thrombogenesis in this PV mouse model and are in line with the lack of correlation between platelet count and thrombotic risk in patients with MPN>>

<<Thus, we are currently developing a clinical trial investigating the impact of NAC in MPN>>

[MPort]

Thank you for posting get this. Very interesting. I read to page 4 which ETGUY has summarised below. I have a couple of comments. First the study does not seem to be aware of the interferon to control MPNS. They only focused on hydroxyurea and anagrelide. So what would be effect of using NAC with interferon in MPN patients. Lastly are aspirin and NAC compatible? I am on interferon for PV. I have taken aspirin for years. I Started taking NAC about 10 days ago. Time will tell what results it has.

[gvibes in reply to MPort]

I am curious with how the NAC works for you. Are you trying to reduce symptoms? Now that I have hematological control with pegasys, I am wondering whether what more I can do about inflammation.

I guess this falls in the category of combination therapies with interferon. This paper, which has been referenced here before, talks about antiinflammatory agents (it mentions ruxilitinib, statins and NAC and others as possibilities) to make interferon therapy more available to people who have problems with it and more effective. It recommends further research in these areas. As others have mentioned and this paper discusses, inflammation is a big deal in MPNs.

journals.lww.com/hemasphere...

take care

[endlessfun in reply to MPort]

What dosing of NAC are you taking? Have you noticed any effects? I have been taking 600 mg NAC 2-3 times per day for quite a few years. Given to me by a functional medicine Doc for inflammation issues and reduced kidney function. Have been considering giving it to my Husband who has ET and on a aspirin only. Curious if anyone else is taking NAC with aspirin.Thanks for sharing.

[tree_top in reply to endlessfun]

I take aspirin every night and I take NAC 600 mg once daily every other day I also use liposomal glutathione several times a week. NAC was part of my everyday protocol during the pandemic. I don't take it as much since I had covid in April.

[endlessfun in reply to tree_top]

Thanks for sharing.

[EPguy in reply to MPort]

I'm taking 1200/day NAC, slow release formula. I'm on Besremi and Dr is ok with this supp. I sense some improvement to misery, esp with the 2nd daily pill.

I don't think the study compared HU and An to NAC, but you're right it did not include it as a state of the art. IFN is still a new idea to some in our field strangely. I still think IFN + Something is our best medium term solution.

Dr Fleishman is running the NAC study. It currently excludes IFN patients, she said she wanted to avoid that extra variable, maybe because it works too well. She has patients on both and says they do fine.

She also told me "don't delay starting IFN" to be in the study.

I'm also on Curcumin. As Hunter and others have posted, Curc can affect blood thinning so that + aspirin (and other supps) should be cleared with Dr.

[endlessfun in reply to EPguy]

My husband is taking Curcumin (500 mg) once a day. I asked the Heme about NAC and he was OK with it. Have not started it yet. He is trying a Ozone & sauna therapy for a few weeks to see if he has any positive effects. Good for detox.

[EPguy in reply to endlessfun]

Interesting on Ozone therapy. Ozone is broadly a corrosive oxidant, used to kill bacteria in water for example. . But it must have some benefits if Dr is ordering it. A quick search I can't find academic reports on it. Did your Dr explain how it works, esp for MPN?

[endlessfun in reply to EPguy]

No the Hematologist did not recommend it. He said it wouldn't hurt to try it. He said same about NAC. My Husband's son wanted him to try it as he had heard of it's potential benefits with detox and cancer in general. We are doing a trial of ONE and will be watching his weekly CBC for any changes in Platelets.

[EPguy in reply to endlessfun]

Let us know if you find a benefit. My intuition is exposing skin to it would cause aging of the skin since it is corrosive, sort of like bleach. It's what you smell on a really smoggy day, at least in 1980s S Calif.

But there may be more complex effects going on that negate these issues. HU is a poison too but has benefits.

[Nikon7ii in reply to MPort]

Good question for a future study of NAC with interferons.