https://twitter.com/abcsoka/status/1664735572231946243?t=U913HttmeBL5eYEm3zHC5w&s=19
According to Csoka it’s due To Chromatin alterations
I can’t load the link but chromatin alterations is basically another way of describing CRPC. CRPC scientists could even say chromatin alterations.
In fact in vitro epigenetic modulation would cure the disease.
There are many other areas impacted required for CRPC progression. In other words there are multiple ways to cure in vitro.
A few observations:
• Many with this condition feel very androgenic before a sudden “crash” into PFS, just like the increase in transcriptional activities necessary for progression towards CRPC
• With PFS many also feel androgenic with anti-androgens and estrogens, just like how in theory the AR ligend binding domain allows binding of other steroid ligends (I myself treat symptoms with estradiol)
• Exogenous androgen treatment can feel like anti-androgens, just like how LNCaP cell line in later stages reacts paradoxically to androgens
Then on top of this all the unique components found in PFS research matches exactly with what is found in CRPC research. That is including the drug itself lol.
Yes. One possibility is that the chromatin surrounding particular genes is in a fragile state after 1st exposure. E.g. there may be a high degree of DNA methylation but not enough to shut down gene expression totally. Upon re-exposure, the chromatin becomes more severely altered.
It’s possible. But even without DNA double-strand breaks there may be hypermethylation of the promoter regions of 5α-reductases, for example (in PFS). But not necessarily enough to shut down transcription. Upon re/cross exposure there may be further DNA hypermethylation.
Csokas quote…goes over my head lol
For PFS, the hypothetical sequence would be something like this: inhibition of 5-alpha reductase protein by finasteride leads to decreased transcription of the 5-AR gene. If chronic, over time the transcription factors that have altered transcription of the 5-AR promoter region…
.will attract DNA methylases (e.g. DNMT3A) to the same promoter regions and induce de novo DNA methylation at that locus, thereby silencing transcription of the 5-AR gene. This process could continue with histone deacetylation etc.
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Yeah epigenetics play into a lot of things - CRPC, schizophrenia, PTSD, bipolar etc.
It’s an area of research to keep an eye on. However so far for CRPC all the HDACi trials have failed with toxicities and I highly doubt that drugs with such symptom profiles are going to be given to us anytime soon officially.
Scientists with a CRPC background can understand the many avenues we could go down, with each one’s limitations. It would be interesting to have Alfonso on an AMA to ask more about it.
We are best fitting in with the most modern research into CRPC the best we can and preparing the evidence for any potential new treatment that emerges. We would piggyback off any treatment that works in the future.
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Thanks for the suggestion and sorry for the slow reply.
It’s not currently possible to host a webinar or AMA with the scientists as they’re too busy. Not only with their studies into PFS, but other work they’ve been involved with prior to their involvement with us. Besides, we’re not convinced of the benefits of hosting such a session anyway, given all they could do is speculate.
It’s something we’ll look to do once we have more results and both have said they’re open to it. In the meantime, the interviews we did with both are a good starting point.
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To go back Tyr comments on feeling better…I noticed only 2 things helped me…Tramadol and sodium bicarbonate
Now baking soda I read helps androgen bind to receptor and I have just now discovered that Tramadol raises estrogen and lowers testosterone…
So maybe that’s why
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Please tell us what side effects baking soda and tramadol have helped with and how did you take them
I was on tramadol after surgery in 2011 i was experiencing erotic dreams and feeling very androgenic this explains why
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Also I tried estroven for a couple days…Unlike tramadol it messed me up even worse…I thought raising estrogen would help but idk if it raises testosterone to simultaneously or what but it worsened my condition…I stick to 3 tramadol a day spaced out…
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Ah damn that’s a shame. All experiences are valid, but I do wonder since I’ve had so many people come to me with significant improvements with E2, if your few days experiment was enough. Especially if you used tablet form, which is so insignificant that it wouldn’t count. I highly doubt it would be E.
Anyhow, I hope you just have a short lasting downfall.
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Have you tried emulating the bipolar androgen therapy they use for prostate cancer research?
I agree with everything in this text, but this theory does not apply to someone who only took 1 pill and had symptoms.
Yes, trialing right now. In general I feel better after the T levels return to castrate and there have been periods of increased sensitivity, libido, smegma, oil, emotions, energy, body temperature / what feels like the immune system etc (a few of which things I’ve not had in 12 years!). I can tell I’m still hypersensitive to androgens.
Also had periods with extreme migraines, which tbh isn’t too surprising given the nature of BAT. Hopefully short term discomfort for long term gain.
Replaced the GnRH agonist which is used in literature for stable E2 monotherapy (enough to maintain castrate level suppression of T) and also using T propionate instead of T cypionate because the shorter half life is seen as more favourable.
I find every 2-3 weeks seems is a good period between T propionate injections. I’m not in a rush with this one and a value the time off between injections especially between week 2-3… Assessing things as they come and if the theory is correct then it seems very promising.
A few others are looking to trial soon too.
It’s likely to take a long time, approx 6 months because this is the time frame it would likely work for certain AR dependent CRPC types, before normalisation occurs.