Calling for Study Participants for First Molecular Level PFS Study EVER ********************

Science PFS Research
#121

RE: Recovery if result is comes back positive

Posted by Awor, 0ct 2009

"From talking with these scientists, it is also very clear that our problem is way beyond the current envelope of basic science. Trying to explain what has happened to us is about as daunting as trying to explain the exact mechanism as to why prostate cancer cells become super sensitive to androgens once deprived thereof. Billions of dollars have been invested into this sole question since over 20 years and we still don’t have real answers. Asking for a research solution to our problem is currently like asking for a cure for cancer. We’ll get there someday, but I doubt it will be in a time frame which is still relevant to us. On the other hand, a breakthrough in understanding the underlying mechanisms behind signaling path changes, in prostate cancer cells for example, could also improve the chances of explaining our problem (this was noted by two of the scientists that I have talked with). Molecular tools and diagnostic equipment are advancing at an incredible speed. Discoveries often lead to further discoveries in a snowball fashion. It remains hard to tell, what advances will be possible in what time frames.

Even though a potential cure currently seems out of reach, it is quite realistic that we can actually prove or disprove the androgen receptor theory and what has happened to us. Gene expression studies are becoming increasingly accessible with a unit cost of around 700USD for materials (multiply that by at least 40 individuals and add salaries/time of specialists and we are still talking six digits). Of course, you still need the scientist that can design the test and interpret test results correctly. On the other hand, given the complex nature of protein interaction at the signaling level, it is not said that our problem can be reproduced in a lab environment (in vitro). Also, if our problem is related to some form of post translational modification (chemical modification protein after its translation), a gene expression study isn’t going to reveal this either. But such a scenario is provable as well, although more complex (statement from lab scientist specialized on executing such studies).

The bottom line to all this is: Our problem is likely to be at the molecular level, an area which is still relatively poorly understood by basic science. In order to get our problem onto the map (an get research going), we need to get something published. As far as I can tell, it is not realistic that a cure will be found to our problem within a useful time frame – even once research has started. However, it is realistic that our bodies can heal themselves (at least in some cases). We must support our bodies the best we can in the process. Given the assumption of this problem, it is also not realistic that a simple doctor has any real chance of helping us. A regular doctor (as opposed to a scientist) is governed by the boundaries of basic science. Even worse, he/she is governed by commercialized solutions (i.e. pharma products) resulting from basic science. So if the basic scientists are still trying to figure out what’s going on at the molecular level, we can’t expect a simple doctor to be able to solve this. Most of us that have been to see various “specialists”, without real results to show for, probably have realized this"

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#122

Well there was very recently a breakthrough in understanding the epigenetic changes behind prostate cancer:
healthcanal.com/cancers/19118-Seminal-shift-how-view-cancer-development.html

#123

I hope Awor feels a bit more positive than he did back then. Honestly, I don’t know what to think anymore. I’ve had a PFS doc tell me I’m going to lead a miserable life (correct so far), I’ve had a researcher tell me they could figure this out in 6 months, and others docs insist they can help me somewhat and had no improvement. I can’t take the ride anymore. I’m just done with it.

#124

At least we should be able to rule something out

#125

Hmm… interesting quote. :wink:

I started talking to scientists somewhere in 2008. It now is August 2011. It took roughly three years of on and off, but in stretches very dedicated field work to get where we are today. It took the papers of Dr. Irwig and Prof. Traish to break the ice. Luck and the behind the scenes support of “40” finally brought us the break through. It took tons of time trying to contact scientists, or actually speaking with them. Parallel to my job and private obligations, I have been taking courses in molecular biology since two years at very reputable US universities and have read somewhere in the area between 150 and 200 papers about topics such as gene regulations, signaling, endocrine systems and many, many papers on cancer. I have written a paper about this problem myself, which is currently the basis for a medical thesis.

So what have I/we since learned or in what way has my opinion changed since this quote of Oct 2009:

First of all, and most importantly, we are doing research NOW. We are in the labs, and this month a fourth institution has joined our consortium and is currently actively looking into the effects at the neurosteroid level. I am simply thrilled by the scientific muscle that we have been able to develop so far, and we have at least 3 high class scientific molecular level potential publications in the works. A scientific conference about this problem is in the works. The subject is really starting to snow ball. If what I am thinking this problem is about pans out, PFS will be called something else and the whole subject will go ballistic. IF. In the best case we are not months but rather weeks away from finding out. In the worst case we are on the wrong track and more or less will move back to square one.

Second of all (and I won’t repeat my previous posts), we are working with a molecular level hypothesis which has the potential of comprehensively explaining this problem. So nobody needs to worry about low 3a-diol-G, low Vitamin D3, wacky hormones, mental and physical problems, etc, because we have all those bases covered. So, IF this works out, we will have explained the basic mechanism behind this problem and can shut down our theory section. This problem could eventually attract the attention of research teams all around the world because the potential implications of what we are looking at are mind boggling in scope and highly relevant to all of mankind. The potential importance of this problem gives me hope unlike anything else.

Let’s just assume for a moment that the results come out as expected. We will then understand the problem at a general level and will have documented the tip of the iceberg. With some further experiments, we can potentially prove some key downstream aspects which will show why we have messed up neurosteroids, hormones and have become variously insensitive to androgens. This is all doable and, given positive results of the first key experiment, just a matter of time and some money.

Given positive findings; The bad news, and this has not changed since 2009, is that below the water there is another highly complex layer which can be composed of interactions between certain proteins, kinases, other enzymes, genes and epigenetic changes which in concert somehow have made this problem persistent. Figuring this one out is not going to be a short term task and will require funding of significant magnitude.

What is likely is that some of the molecular behaviors involved in our problem are the same as those involved in cancer. This need not worry us, nobody is saying that our problem will lead to cancer. Many things have to come together for cancer to develop. But if we can find some common denominators, and we are currently looking at a potential one, we can ride the coat tails of existing research and pharmaceutical developments. We have no chance at developing treatments from scratch to solve or at least alleviate this problem. We need to leverage existing research and trials.

So in summary, my hope currently is that we are dealing with a form of molecular behavior which is already known in the context of other diseases, and that we can use existing treatments to help in managing this problem. It will, however, take more brave men to try out prospective treatments in order to see if they really work in our context.

Having said this, I would like to close this post by explicitly giving support to all the anecdotal trials that many of you are enduring through. Every now and then, somebody seems to respond positively to some form of treatment he found, either alone or together with his doctor. This is extremely valuable (minus the theorizing) and remains the backbone of our community. In other words, we need to follow a two pronged approach: People trying out things in an attempt to find something that works, and a scientific approach with the objective of really understanding this problem. Hopefully the scientific approach and better understanding of our problem will give us more insight into where to look for promising treatments.

#126

Great stuff. I think it’s absolutely essential that we all carry on chasing doctors, getting blood tests and as many of us do, try things ourselves. This is all down to each person of course. Personally i would be happy to put myself forward as a guinea pig :laughing:

If this research doesn’t go as hoped, will we be able to at least officially rule out androgen resistance? also, how does the androgen resistance theory fit with those who have experienced weeks and even months of feeling better (fluctuations)? I also remember you saying that you are improving somewhat Awor, i would be curious to know whether this improvement has persisted.

#127

Hi Awor.

Firstly thanks for all your tremendous hard work!!

Would you happen to know if this theory rules out the possibility of a natural recovery? I noticed with your posts in ’09 you were fairly positive about this possibility, and just wondered if this theory throws it out? or if you had a view now. Thanks

#128

It is clear from the clinical manifestations of this problem that we have some form of androgen resistance. Lacking or blunted response to androgens, which at least many of the men here have, is called androgen resistance. The question is not really if, but rather how this is happening. That is what we are looking at.

They did until I tried Milk Thistle. MT reduces AR transcription rates, which initially made me feel even better. Doing that seemed to have the same effect as if I had taken fin or sp. So right now, some side effects have gotten worse again. Mentally I am doing pretty good though. I hope I will recover from this MT trial soon (only took a few pills).

It’s clear that the body has an ability to correct this in some cases. I have gotten better to some degree and while preparing this research, we contacted a few guys to participate who aren’t active on the forum. Of those guys, two had recovered in the course of the last two years (without treatment it seems). Maybe there is something more we can do to help the body in recovering. Hopefully a better understanding of this problem will give us additional insight in this area as well.

#129

Always good to hear!! :smiley:

#130

You should really get more info. on this. It seems that true recoveries are few and far between. It would be nice to know exactly what/how they did it, what supplements they were taking, etc., etc…

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It would be nice if the study came back positive because for once we will positively know what has happened.

But at the same time I sort of hope it doesn’t. Sounds like a lot of years and $$ to find out the deeper implications and even more after that to find a “fix”. And this all depends on whether we can keep the researchers on our side, keep the funds up, and find relevant current research.

Awor, if this theory comes out to be true. Is there a series of non-molecular tests that others can use to prove they are suffering from the same problem as PFS guys? For example, there are a lot of other forums that have cases that sounds so similar to our, but they either used other medications or some even just had illnesses that brought similar PFS symptoms on. Would they be able to get 3a-diol-g or any other similar test done to see if this same mechanism is at work? Or perhaps the skin fibroblast tests are cheaper than I expect?

#131

This is a very good idea.

#132

Awor,

Thanks for the response. I wanted to dig out your post from 2009 to see how you felt today about things. Obviously you have put in some seriously hard work, I have so much respect for you.

Im a follower of the Prostatitis theory and I believe that some of our symptoms come from CP. However, I think if your results are positive then that must be the overiding cause of our CP and everything else we are experiencing.

#133

As this has been said i may as well mention that i have messaged a lot of guys that don’t usually post on the forum but are still active and a few of them have made big improvements. I also PM’d a number of users that haven’t logged in for a year or two so you never know, i may get replies from them at some point too.

#134

Yes. The hallmark of our problem is that supplementing androgens doesn’t have a normal effect. I am in contact with other patient organisations and can say that this is the case with:

  • Accutane / Roaccutane (isotretinoin)
  • Antidepressants (SSRI’s and others)
  • GnRH Antagonists (Lupron, etc.)
  • Estrogen treatments with woman (including birth control pills)

These problems affect both men and woman, and the more severe cases show no or even negative response to androgen supplementation. The side effect profiles are very similar if not identical to ours (in severe cases). Once we can establish the theory for finasteride, there is definitive interest to start investigating the others as well. That is what I mean by, this is one big huge problem, much larger than only finasteride (and only indirectly related to 5AR). Of course, there potentially are other diseases which cause similar problems to ours. I don’t have a complete overview of all of them. But if you find people suffering from the same problems as ours, and androgen supplementation fails with those patients, I would be VERY interested to hear about such cases. Please pm me with anything you may find in that direction.

#135

lupronvictimshub.com/

This seems to be the only such patient organisation for this drug. Read this funny quote: “I also worked very closely with the National Lupron Victims Network from 1994 to 2000, when they, their 10,000+ “lupron victims’ surveys”, and all my provided research information, inexplicably disappeared.” Seems a drugs company has ‘got at’ a similar patient website in the past!

A state of permanant hypogonadism doesnt seem to be listed as a side effect of this drug on this (badly laid out) website. I would be interested to see any information that shows it can (other than sexual side effects of course).

#136

Thank God for science.

Would a genetic comparison between those who are “stuck” and those who recover likely reveal any potential targets for treatment? Are any such genetic tests currently planned as part of the research project?

Oscar, this is a link to the discussion about androgen ablation syndrome: http://www.propeciahelp.com/forum/viewtopic.php?f=1&t=5292&hilit=androgen+ablation+syndrome Mew and annon posted some information about men who used lupron and developed permanent sexual sides in lieu of normal testosterone levels.

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#137

Permanent sexual dysfunction as the result of using anti-androgens is not suprising.

But nowhere on the internets can I find any information that androgen deprevation can cause the other permanent side effects (brain fog, anhedonia, muscle loss) or anything about a ‘crash’ after stopping. (Maybe the only exception to this is accutane). Is Awor saying he has some evidence of lupron causing such problems? If so, that is HUGE.

#138

A man prostate cancer undergoing androgen ablation on Lupron has the same awful sides that some of the worst on here get. As well as weight gain, ED/zero libido, depression as to be expected with castrate T levels, interestingly many report stuff like insomnia and stomach problems like many of us do. Many also report hardcore brain fog, with loss of creativity and emotions similar to ours alongside the cognitive problems. Many men are actually reluctant to take it or want off it even though it is supposed to prevent DEATH.

Here’s some of their experiences:
askapatient.com/viewrating.asp?drug=19732&name=LUPRON%20DEPOT&PerPage=60&sort=age&order=0
prostatecancerblog.net/?p=23

I haven’t really seen a rack of complaints of permanent sides, although I see some mentioned here and there. Men usually take months to get their libido back. As oscar says, many doctors will likely right it off as the man getting old, as I’m sure pharma would want them to. I had thought it encouraging that men could have such extreme sides and get their bodies to revert back to near normality, but now I’m not really sure if it happens, and besides we are different in that we acquire the worst problems usually after we quit.

Presumably the same process is at work with women who take it for endometriosis. It’s actually quite scary how common the stories of ruinous long term sides are there and yet nothing has been done.
ipetitions.com/petition/depot-lupron/signatures?page=20

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#139

All very interesting stuff here. I can’t wait to see what comes back from these studies… Further studies on say, the prostate, will also be very interesting.

The link to Lupron is also compelling, its just you don’t see many young males taking it so its hard to really know if it’d cause the same sort of issues. As said, its likely that old age and long lasting sexual issues would likely be attributed to age and not the drug.

#140

I find it quite surprising considering the amount of people that come off them or use them for years and years without side effects.