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Author Topic: Navitoclax (ABT-263) induces apoptosis of fibroblasts  (Read 1358 times)

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AlmostBlue

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Navitoclax (ABT-263) induces apoptosis of fibroblasts
« on: March 11, 2018, 01:10:24 AM »

https://www.ncbi.nlm.nih.gov/pubmed/29237758

https://medicalxpress.com/news/2017-12-drug-apoptosis-myofibroblasts-fibrosis-scleroderma.html

Pushing cells to self-destruct combats deadly fibrosis | Science | AAAS

https://sclerodermanews.com/2018/01/11/cellular-self-destruction-trigger-explored-as-scleroderma-treatment/

Very interesting stuff. There are a few other articles out there. You guys can search something like "navitoclax fibrosis" and check them out. I am surprised this hasn't been posted yet.

This is very similar to the discovery of the anti-CD47 antibody and its ability to reverse fibrosis. There is already a thread on that in this section. Both new, non-FDA approved anti-cancer treatments work in a nearly identical way when it comes to eliminating fibrosis.

If you do a google search, Navitoclax can be bought online from chem suppliers it looks like. In the anti-cancer trials they did 120mg per day, if I remember reading correctly. It was well tolerated and the main side effects were dizziness, nasuea, etc. The possible side effect that caused alarm was that this drug can reduce the # of platelets with high doses.

Would trying a dose like 40 or 50mg per day for something like 5 days be a bad idea? I am pretty desperate at this point and I wonder if this could be a real fix. I have no intentions of that and I am not advocating for anyone to try, I would just like to spark conversation.

Between Navitoclax, the anti-cd47 antibody, that E4 peptide, I am a tad on the optimistic side for ridding ourselves of this horrible disease. These 3 drugs seem to be ways for the body to reverse/get rid of the fibrosis altogether. Additionally, i am optimistic for mediwound's mwpc003.
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Paolo

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #1 on: March 11, 2018, 04:21:13 AM »

AlmostBlue, this is your first posting, to avoid conflict of interest can we have your story, do you have peyronie's ??? ???

If you want to 'spark conversation' let's have 'your' story please  :)
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skunkworks

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #2 on: March 11, 2018, 08:36:30 AM »

Had not heard of navitoclax, thanks for the heads up. It certainly does seem like it could be interesting with regards to Peyronie's, but I doubt it will be safely available for quite some time. Definitely not playing Russian roulette with black market suppliers.

Crooked_Stick

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #3 on: March 11, 2018, 10:59:47 AM »

Good post almostblue, I believe there will be a cure for Peyronies Disease...as I’ve stated before, MWPC003 has huge promise....itis the same enzyme used in Mediwound’s Nexibrid ans Escharex which are in phase II and III....they are waiting to get their first two products to market before proceeding with the injectable version that will be used for connective tissue disorders including Peyronies Disease.....I believe that MWPC003 could be used to dissolve the plaque followed by a stem cell treatment to grow blood vessels and nerves
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pey ron

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #4 on: March 13, 2018, 03:50:13 PM »

@AlmostBlue: can you please send me a PM (private message) with all the websites where you have found this drug so far?

To send me a PM, just click on the symbol under my name to the left of this reply.

thank you!
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hope794

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #5 on: June 03, 2018, 04:57:31 PM »

Anyone got news about this? Are they going to open trials?
If anyone knows something, please share.
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24 yo from Italy.Peyronie's probably since 2014.Since then,penis bends of about 10-15°, with a slight twist to the left.Moderate Erectile Dysfunction since 2 years and things getting worse.From pornstar-like to moderately depressed,but still fighting for a solution.

Werther

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #6 on: December 03, 2018, 11:27:43 AM »

Is there any way to purchase this? It looks like it's been around for quite some time so far (e.g. ABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor | Cancer Research).

Can a doctor prescribe it? Maybe an oncologist?
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Cacogen

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #7 on: December 19, 2018, 01:27:19 AM »

Do we even know what specific anti-apoptotic proteins need to be targeted in Peyronie's myofibroblasts? Navitoclax might not block them, or not block them all. If this were likely to work well on all types of pathological fibrosis, I would think there would be papers out already studying efficacy in rodent models of idiopathic pulmonary fibrosis -- which is of course quite deadly.

Tempting though it may be, I'm not sure I would self-experiment -- Bcl-XL inhibition can cause thrombocytopenia:

Because navitoclax inhibits Bcl-XL, it reduces platelet lifespan, causing thrombocytopenia, and this makes it dose-limiting.

https://en.wikipedia.org/wiki/Navitoclax#Mechanism_of_action

You would want to make sure you got dosages right, and I'm not sure it's clear what the correct dosage would be, because this was a rodent study, right?

Interestingly, navitoclax also appears to be a senolytic agent, selectively destroying senescent cells -- just in case senescence plays some role in Peyronie's pathology.

Inducing myofibroblast apoptosis does sound extremely promising. It might even cure Peyronie's -- or perhaps stop and reverse a significant amount of the fibrosis (possibly Peyronie's-deposited ECM proteins are harder to reverse than those from scleroderma?). 
 
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