Azacitadine

Therapeutic Efforts Pharmaceutical
#1

If methylation is the most likely initiator of our issues and if procaine helped Awor albeit briefly is their a warrant for the use of Azacitadine - a more potent demethylating agent?

Would a brief course indicate whether we are on the right track here? If it is a brief course then the epigenetic changes will most likely not stick as they will remethylate. Is this so?

Procaine is substantially weaker than azacitadine. I have been thinking about going for procaine therapy and have made inquiries. Procaine is not only weaker but has shown to be potentially less global in its function:

cancerres.aacrjournals.org/content/66/5/2794.full

It is possible that procaine affects DNA methylation only in a subset of human cell lines, like the MCF-7 breast cancer cell line

I understand there are risks of hypomethylation and causing an altered immune system but i thought i would start this thread as a discussion.

If indeed research indicates there is an epigenetic problem with methylation there are currently no other specific solutions. Nearly all demethylating agents are very blunt instruments.

#2

Getting miles ahead of ourselves of course, but this is a bit interesting regarding combination therapy.

hopkinsmedicine.org/news/media/releases/combination_epigenetic_therapy_clinical_trial_results_

“We showed in the late 1990s that if you got rid of the abnormal DNA methylation first, and then used a histone deacetylase inhibitor, you could enhance the re-expression of these abnormally silenced genes,” Baylin says.

Unless I misunderstand there are two ways to epigenetically silence gene expression- the addition of methyle groups directly on the DNA and tighting of the histones surronding the genes. When the day comes we attempt treatment maybe we will need to address the mehylation via something like Azacitadine and then address histone deacetylation.

#3

Getting miles ahead of ourselves of course, but this is a bit interesting regarding combination therapy.

hopkinsmedicine.org/news/media/releases/combination_epigenetic_therapy_clinical_trial_results_

“We showed in the late 1990s that if you got rid of the abnormal DNA methylation first, and then used a histone deacetylase inhibitor, you could enhance the re-expression of these abnormally silenced genes,” Baylin says.

Unless I misunderstand there are two ways to epigenetically alter gene expression- the addition of methyle groups directly on the DNA and tighting of the histones surronding the genes. When the day comes we attempt treatment maybe we will need to address the mehylation via something like Azacitadine and then address histone deacetylation.

#4

This is very interesting to me. Would dr.s try something like this as an experiment? or do we need further research to make sure theat methylation is the root cause? I’m going to the mayo clinic wednesday and would like to talk to the endo about something like this as a possible treatment. I’m afraid he will be like many of the other docs and suggest trt or some sort of other hormone type of treatment that will not treat the underlying cause of this condition, I will try anything to beat this. This seems to me to atleast be part of the problem and sounds like this treatment or procaine can help.

#5

I believe Awor has already mentioned the first step to this would be to identify which genes are expressed incorrectly. I think this is one track the research is on. And, I am assuming we have already narrowed PFS down to being epigenetic in nature and not genetic in nature (as in AIS) by checking suspect genes for various mutations. I doubt any endo would perscribe them though. To be honest, I really have no idea how these medications work and how possible it is to target specific genes at this point.

Shippen had me injecting Procaine subq which didn’t help and Awor has posted his experiences with IV procaine treatment. I’m too lazy to look up the thread but I believe he felt better in most all areas, particularly mood, then he pretty much went back to baseline.

#6

I understand that they are researching this and narrowing down which genes are silenced, but even if we do know which genes are silenced globally treating this to change gene expression could still be beneficial right? if we don’t use dangerous amounts of procaine/azacitadine? Along with nystatin or another hdac inhibitor. I don’t really know what i’m talking about but this sounds logical to me and worth a shot.

#7

I’m not the expert on this stuff but global demethylation has it’s own dangers. Expressing the wrong genes in cells where they should be silenced I’m sure could lead to some big problems. I think there is probably a ton of research and questions we need to have answered before consider this stuff. Still, it’s interesting to consider. Hopefully we catch some huge breaks along the way as epigenetic research accelerates.

#8

So this means we’re kind of at a stand still with this treatment process? And determining a treatment will almost be impossible until we find the root cause i’m guessing. I just want to be able to convince my dr. i’m seeing tomorrow that hormones aren’t the answer to solving this problem and see if he can’t figure something out with this.

#9

With that said, if they could block all 5ar in a rat or some kind of test subject, to the point dht is non existent and see what is blocked or shut off after that then they should be able to figure out what happened. Finasteride is a drug with inhibitory effects and once the inhibition is complete it would find something else to inhibit right?

#10

Selling an endo on the gene expression arguement can be frustrating. I’d hope since he’s at the Mayo clinic he at least is opened minded. I could be wrong but I believe low 3 adiol G is a result of the under expression of the AR gene in a sample of PFS patients. You could tell him we all have very low levels of that metabolite of DHT and we’ve found (according to Awor’s thread) “something” wrong the the AR gene against a control group. Of course tell him about taking Fin and the change of gene expression via negative autoregulation when DHT flooded back. If you havn’t yet had a full hormone profile done definately do that. Try to get him to also test vit d levels and your 3 adiol G if you havn’t already.

#11

viewtopic.php?f=8&t=6612

This abstract doesn’t discuss mechanisms at molecular level but it shows what type of changes can occur in erectile function due to 99% DHT reduction via Dutasteride.

It does note that “cholinergic and adrenergic responses remained depressed” even after quitting.