Reversing silenced AR signal with demethylating agents - A promising treatment option?


#1

For all those that can follow on the line of thought, that some form of silencing of the AR signal is at the root of our problem, there might be some hope. The main molecular mechanism behind persistent epigenetic changes in gene expression is DNA methylation. As methylation is also implied in cancer, much research attention is going into the question of reversing this process through demethylation via demethylating agents.

I would like to dedicate this thread to the subject of such demethylating agents. If anyone finds interesting information on the subject, please post it here.

A real “here and now” treatment option is Procaine (Novocaine):

cancerres.aacrjournals.org/conte … /4984.full
en.wikipedia.org/wiki/Gerovital_H3

If anything promising has come along my way recently, this is it. I am going to try to get my doc to shoot me up with this stuff.


#2

Nice Awor! Worth a shot bro…We can’t import this though right? There is a FDA ban I believe…


#3

What exactly does this have to do with the androgen receptor, specifically? Not asking this sarcastically…


#4

looks like you can buy injections from overseas…zalmo.com/4.html


#5

Is the Procaine (Novocaine) the same as the dentist uses to numb your mouth? The link you provided states:

Since Novocaine is not banned (I assume) what is the difference between Gerovital H3 and Novocaine? There are some other demethylating agents listed on wikipedia:

en.wikipedia.org/wiki/Demethylating_agent

This article claims that ECGC in green tea can be used as a demethylating agent for one specific gene (how do we find the right demethylating agent for the genes that fin has methylated?) I’m totally ignorant on this so excuse me if I’m rambling.
ar.iiarjournals.org/content/29/6/2025.full

This is a pretty decent article on demethyating agent and cancer:
anti-agingfirewalls.com/2009/11/ … t-cancers/


#6

How would this work in practice? Just simply shooting novocaine to reconnect with androgen response?

youtube.com/watch?v=V2yy141q8HQ


#7

Awor, the epigenetic changes argument is a very interesting one. I spent several days reading about it some months ago. It was interesting to take away a very different understanding of genetics and the way DNA operates over generations, as most of us grew up believing that these things were immutable, and they are not.

From what I remember, there were studies that showed the ineffectiveness of some of the more common “demethylating” treatments… but then again, I suppose most treatments have “studies” that contradict each other on effectiveness. If you find a treatment that doesn’t appear to present a health risk for you, and you are willing to try it, I say go for it, and keep us posted. I find the topic fascinating.


#8

Turns out some of those trans fats may be good for you.

mct.aacrjournals.org/content/9/5/1256.abstract

en.wikipedia.org/wiki/Trans_fat
Fry your dinner in some vegetable oil and have some green tea (EGCg) with it.


#9

This has to do with silencing of AR signal, which is the basis of the androgen insensitivity theory. It has been proposed by scientists that drug induced persistent side effects are due to epigenetic changes in gene expression levels, specifically by DNA methylation. Note that this paper specifically talks about isotretinoin (Accutane, also a 5ARI class drug) as causing such problems. I had contact with the author of this paper and he also suspects finasteride as causing such problems.

Hence the idea about reversing this with a demethylating agent. Fortunately for us, many cancer forms are associated with hypermethylation of certain DNA segments. As most research $$ go into cancer research these days, we can hope that therapy options coming out of there could be useful to us.

My thoughts on this: Perhaps the root-root cause of our problem is an overactive Methyltransferase enzyme, which goes about hypermethylating DNA more actively than it should. Proof of this would be an unusual high incidence of cancer cases with persons in our blood line (parents, brother, sister, grandparents, cousins). Does that fit anyone?

Following quote gives the link with AR silencing further credence:

5-aza-2 is a commercially available under the brand name Dacogen: cancer.gov/cancertopics/drug … decitabine
en.wikipedia.org/wiki/Decitabine


#10

Thanks for the explination - are you attempting to find a doc to try a demethylating drug? I see it is iv admin only. Also, is there a way to test for hypermethylation? I very much admire the fact that you wrote the researcher btw, kudos.


#11

Yes, and I have already found a medical center near my home that offers this (IV) on the basis of Novocaine. Will investigate this for August, but want I to discuss this treatment option with another scientist first.

Sure. You’re new here I think, so let me tell you that there is a lot of effort going on behind the scenes to get science more involved. I am part of this effort. It is very long term and slow progressing work though, so there unfortunately is not something to report every month. Research also eventually requires patient groups to participate in studies. We’re getting to a point where we will need to know who we can count on to participate in such studies. The amount of effort it took to get people to register for a simple telephone interview with Dr. Irwig was disconcerting. There is going to be an announcement about this soon.


#12

My thoughts on this: Perhaps the root-root cause of our problem is an overactive Methyltransferase enzyme, which goes about hypermethylating DNA more actively than it should. Proof of this would be an unusual high incidence of cancer cases with persons in our blood line (parents, brother, sister, grandparents, cousins). Does that fit anyone?

No one in my family has had cancer. I was pretty healthy and probably destined for a long life before this crap, always tried to eat well and exercise reasonably well.

If novocaine did help how would it relieve symptoms?


#13

Have you also considered methylation testing prior to the novicaine treatment? I saw a methylation pathways test is available for 300 online.

I have also seen through some googling that low histamine is a common factor on the overmethylated - perhaps it’s worth testing


#14

Awor,

You can count on me to participate in any study. I will respond very quickly.

Thanks for all of your efforts, it’s appreciated.


#15

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#16

I think a lot of people attempted to participate in irwigs survey but were intelligible, like myself, due to strict restraints such as not being on any other pharmaceuticals. Im sure we will all participate in any promising treatment options in the future.


#17

Does anyone have access to the full paper here?

sciencedirect.com/science?_o … ee88858cc6


#18

Perhaps valproic acid, a commonly prescribed pharmaceutical for epilepsy, is another option for demethylation:

medscape.com/viewarticle/538458


#19

maybe folate levels should also be tested, it looks like that in excess folate has the potential to hypermethylate:

researchprofiles.collexis.co … 8&o_id=55&


#20

It looks like valproate and 5-aza-2’-deoxycytidine both have an effect on reversing leukemia via demethylation as well. It includes some valuable information on effective use of a demethylation agent in re-expression of a gene (at least in the leukemia context) which, perhaps, may enhance the effectiveness of any treatments which we may try in the future.

bloodjournal.hematologylibrary.o … 08/10/3271