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 (http://www.sciencemag.org/news/2017/12/pushing-cells-self-destruct-combats-deadly-fibrosis)
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.
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 :)
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.
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
@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 (https://www.peyroniesforum.net/Themes/core/images/im_off.gif) under my name to the left of this reply.
thank you!
Anyone got news about this? Are they going to open trials?
If anyone knows something, please share.
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 (http://cancerres.aacrjournals.org/content/68/9/3421?ijkey=ae7fe5d56754712e6dbf4a9b060ebf7ce7eed386&keytype2=tf_ipsecsha)).
Can a doctor prescribe it? Maybe an oncologist?
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?).
I personally don't know if anything's being done with regards to this whole subject but it looks like some other steps were made further from the researchers working on this molecule.
Here is what I found: this is the first study to demonstrate that PF can be reversed by a senolytic drug such as ABT-263 after it becomes a progressive disease. Therefore, ABT-263 has the potential to be developed as a new treatment for PF (full text: https://www.ncbi.nlm.nih.gov/pubmed/28479002).
Then,you can see that, within the same year, it was reported that "Using a BH3 profiling assay to assess mitochondrial priming in dermal fibroblasts derived from patients with scleroderma, we demonstrate that the extent of apoptosis induced by BH3 mimetic drugs correlates with the extent of their mitochondrial priming, indicating that BH3 profiling could predict apoptotic responses of fibroblasts to BH3 mimetic drugs in patients with scleroderma. Together, our findings elucidate the potential efficacy of targeting myofibroblast antiapoptotic proteins with BH3 mimetic drugs in scleroderma and other fibrotic diseases (full text: https://www.ncbi.nlm.nih.gov/pubmed/29237758).
Now, having passed two years from the abovementioned papers, do you think that maybe any of us should get in contact with the authours of these studies in order to ask them - at the very least - if peyronie's fibrosis applyes to the mechanims of action of this drug and if their reply would be confirmative - as I hope - some of us could maybe get enrolled in their trial and then report to the forum!
What do you all think about this?
Great question Werther! Is someone willing to do what Werther said?
While we find a way to get navitoclax or dasatinib, natural products with similar activities:
https://docdro.id/HtLwzZB
Thanks for the infos, pey ron.
Just one question that, apparently, was missed by everybody: is this drug actually marketed?
Put in layman's terms, can you actually buy this from the producer a franchisee or any other legitimate source or is there only the dark web (and its associated risks) for this?
I hope that anyobody with some knowledge on the subject can chime in and give helpful information. It would be helpful for everybody and it would be very appreciated.
If enough of us are willing to experiment, we could do a group-buy from a chemical supplier. I have contacts that have run mass-spectrometry tests and looked for solvent residuals several times before. But first we would need a good number of pioneers to achieve economy of scale.
This looks very promising, i posted multiple times in development drugs section about some researches about other possible treatmants like dickpof and ab007 but i dont know why they pop out with this researches and after that zero, nada , it looks like there is multiple promising treatmants for peyronie disease but in my opinion the cure will come secundary to primary cure fore other conditions like lung fibrosis etc... it really sucks because i seen dozens of potentional cures and thats it ,no further research....so i dont know what we can do to change that?
Quote from: pey ron on August 24, 2019, 01:11:03 PM
If enough of us are willing to experiment, we could do a group-buy from a chemical supplier.
I agree with you but IMO this would only be really useful for drugs that are currently out of the market (nobody is producing them and they are not being sold anywhere).
Navitoclax however has been around for at least a decade (it has been tested on a clinical trial in 2009) so I don't know how worth is the risk experimenting with a synthesized compound supposedly similar to it when you could actually get your hands on the real thing. The same goes for other drugs out of there that sound promising.
That's why I was asking the above. I hope there's anyone who have info and can reach out. Send me a PM in case.
how can we actually get our hands on it? no doctor will prescribe it off-label because they will all be afraid of liabilities :(
You are right but the same goes for other drugs that might be potentially useful but have never been experimented with regards to peyronie's. I'm thinking of metformin as an example: nobody (I'm talking about the medical community) ever tested it for peyronie's so you would never get an urologist to prescribe it for peyronie's but nonetheless there are ways to get it since it's on the market (e.g. you could trade it with diabetics or go as far as to falsify prescriptions in order to get it).
I think the same could be done for Navitoclax. Maybe a joint venture with scleroderma's patients could help... ::)
Can anyone find out where to buy this stuff?
Alibaba has some, but that is shady and uncertain. However, I might try that route...
There are tons of US labs that can supply it, but they will only ship to researchers with a university or company address, etc.
We need to group together and find some urologists who will help us
Why might net for in be helpful? It's cheap and readily available, helps stabilize high glucose AND has anti-cancer properties (week researched).
Actually, Navitoclax costs a lot. We should create an "experimental group", make a "group buy" and test it with safe dosages. Maybe something cool will jump out from that..
Invivochem seems to be the cheapest. 250mg for $450 and 1g for $1300. The issue is they will only ship to universities or research companies I think. Not sure how to circumvent this
Quote from: AlmostBlue on October 01, 2020, 03:42:45 PM
Invivochem seems to be the cheapest. 250mg for $450 and 1g for $1300. The issue is they will only ship to universities or research companies I think. Not sure how to circumvent this
Almost, what about the dosage? I can't find any study with the correct dosages. And what about the sides..
a recent trial gave 325-425 mg/day for 21 days. They reported no adverse side effects
Can you please provide me the link of the study? Thanks, bruh.
https://ashpublications.org/blood/article/116/21/3943/67683/Navitoclax-ABT-263-Plus-Rituximab-Interim-Results
"Navitoclax was given once daily at 200 mg (Cohort 1), 250 mg (Cohort 2), or 325 mg (Cohort 3)
Seventeen pts (patients) had navitoclax-related AEs, the most common being diarrhea (11 pts), nausea (11), and fatigue (8). DLTs were Grade 3 diarrhea (1 pt in the 250 mg cohort), Grade 3 fatigue (1 pt in the 325 mg cohort), and Grade 4 thrombocytopenia (1 pt in the 325 mg cohort)."
Thrombocytopenia is serious but it only occurred in 1 patient. This is dose-related and will correct itself upon stopping the drug.
Nice informations, but i fear that these dosages of Navitoclax will cost A LOT.
Guys -- I'd like your help on dissecting the data on BCL-2 in this study: http://www.advances.umed.wroc.pl/pdf/2012/21/5/607.pdf
I am having a hard time wrapping my head around the figures for BCL in peyronies plaques. Would love someone who is sound at statistical analysis to chime in.
Keep in mind, all patients with Peyronies Disease in this study have had their plaques 1 year or more. From what I've read about scars, they express BCL proteins highly in the early stages, and then BCL levels taper down as the fibroblasts grow older and stabilize. I.e. an established scar of 2 years will barely be expressing any BCL. I think I read this somewhere. I will try to locate the studies that say this.
...
I found another study that showed low BCL expression in peyronies plaques (scroll down to "3.3 Bcl-2 expression")
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147380/
Important to note, all patients in this study had "stable Peyronies Disease for at least 6 months". When does Peyronies Disease usually become stable? 2 or 3 years is the average right? If so, this means these samples were taken from patients with 2.5-4 year old plaques. Someone chime in on this, this would confirm that old & established Peyronies Disease plaques express low BCL protein levels.
Doesn't the acute stage only last 6 months to 1 year? Given all this above, I am now thinking that Navitoclax would only work in this initial 6 month (or so) period of getting Peyronies Disease. I am willing to bet if they sampled a 3-month old Peyronies Disease plaque it would have high BCL-2 levels.
I recently got a new plaque 30 days ago, so I very well may end up trying Navitoclax soon.
AlmostBlue, BCL-2 genes can be either pro apoptotic or anti apoptotic. It depends on what is expressed. We're trying to make pro-apoptotic genes high, and anti-apoptotic genes low. Navitoclax can do this, but TBH i don't know which dosage would be correct to reach our goal.
I think its CRAZY that no one is experimenting this for fibrotic diseases such as Peyronie's or Dupuytren's. F~@< this crap.
Can someone versed in this field tell us the risks in trying this drug?