Phase III and IV coming from Melcangi/Fundraiser

Last paragraph hit the nail on the head

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Can someone explain why there’s complaining when this guy is studying things for us? Not many are what’s the issue ? He’s doing things and posting results

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Yeah at least he tells ya something…I think a lot of people are just worn down and on their last legs here hoping for the root and are frustrated that these studies seem to look more at the symptoms of pfs…But as many are aware this takes time like building with legos or putting a jig saw puzzle together…Each study builds and learns from the last…people want to know the root cause is the frustration…

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I will try to explain in a couple of days when I have more time. For now, here is a possible criticism, which may or not not be valid. The point needs to be argued, and I hope I will soon.

  1. These studies will not find a cure.
  2. These studies are not looking for a cure.
  3. These studies are not deigned to find a cure.
  4. Some of these studies are not only not designed to find a cure, but are also not designed to find anything relevant to PFS.

At the same time, these studies cost tens of thousands of dollars. Every benefit has a cost associated with it. The goal is to invest money and time in the most efficient way in order to meet the highest priority goals. The money used by these studies can be used to meet the objectives not being met above more effectively.

The alternative is to fund a rat study testing 10-20 treatment protocols. This kind of study has a significant double digit chance, in my opinion, of finding a cure or at least an adequate treatment within a year. Even if it doesn’t, it will still be a a huge success because it will prove that everything everybody is currently doing won’t work, including CDnuts, including the famed doctors charging 600 dollars, including all the supplements you buy. And then all that wasted money, which is many multiple orders of magnitude more than what the rat study will cost, can be channeled into fundamental research, once people have solid evidence their current efforts are in vain.

What is the chance that Melcangi’s microbioata study will result in a cure within a year? Zero. What is the chance it will contribute to ever finding a cure? Zero.

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do you think it is curable in the future ? like in 10 years ? otherwise i will do something. going to jail forever is no problem any longer for me. and i will do it. i cant kill myself but i cant cope with these headaches. i need to do something

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Unfortunately, I also fear …

That depends on the study.

In order to find a cure (through scientific means), we need to first precisely identify the root cause. Ablating androgens with finasteride (or sp, accutane, ssri’s, etc.) has changed something in our bodies, to put it high level. This change is very likely some epigenetic effect in our cells. Environmental factors (chemicals, medication) have been shown to induce epigenetic changes in countless publications, this is undisputed. Epigenetic changes can persistently alter the way our cells work, and thereby the function of our organs (which are obviously made of cells).

Given the above, the big question is which genes exactly are deregulated, and which genes predispose us to this mess in the first place, given than most guys can take these meds without any negative effects (which still amazes me). Studies which are looking into these questions are by their nature paving the road on the way to finding a cure, or at least some half way effective treatment.

Where I unfortunately have to agree with you, is that Melcangi’s studies do not fit the above criteria. His studies so far have been designed to demonstrate the effects of finasteride and pfs in patients. Such included demonstrating altered neurosteroid levels, methylation of 5ar and altered gut microbiota. This undoubtedly is valuable at a scientific level, makes for some cool publications, and is important for keeping the conversation going in the scientific community. Such information can also be useful for potential future law suits, but it doesn’t pay in well to our “cure” objective. Therefore I feel that we need to keep our expectations regarding Melcangi’s work at a realistic level.

Brigham and Women’s Hospital, Baylor and our own community GWAS project on the other hand, theoretically fit the bill. Needless to say, Brigham was a total flop. Baylor, on the other hand is looking into full genome gene expression, and is therefore 100% on mark with regard to what I wrote above. The problem of course with Baylor is that the study has been going on forever, and is frankly way overdue. I am still hopeful though, that they will end up publishing the goods in the near future. If the publication will not be muddled by political factors (as seems to have been the case with Brigham), the Baylor study could be the scientific equivalent of a Tsunami. Let’s keep our fingers crossed.

Last but not least comes our very own community GWAS project. With some more genomes, and collaboration of the right specialists, we could have a chance of finding some underlying genetic drivers to our predisposition. This would be key to developing an animal model. Melcangi has been feeding finasteride to a bunch of rats, and has shown that they show some depressive symptoms. However, it would not be reasonable to call this PFS. One could only start talking about PFS if the effect (along with other typical PFS symptoms) would persist for many months after discontinuing the drug. This not have being demonstrated to be the case, we cannot be talking about an animal model here. An animal model would need to be genetically engineered to mimic our predisposition, and then “get” “real” persistent PFS once being administrated these drugs.

At the end of the day, we cannot put all of our egs in one basked. We need different baskets: Bespoke ones, scientific ones, community made ones and also some luck. With all those ingredients, in the right mix, I believe that we have the best chance to advance.

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thank you awor. as you mentioned the rat problem, im maybe a help. i had the same problem like these rats with daily finasteride. depressive behavior. but when i cycled it pfs occurred. and that was the case in many members of a german hair loss forum. first the rats have to take finasteride long enough to get hypersensitive dht receptors( 300 days or so) then you give the rats 3-4 times : 3 weeks propecia , 1 week not (like girls take the pill) and then again 3 weeks propecia 1 week not and then let them quit, the most will develop this crash. might be a try ? i think it could work due to the hormonal fluctuations we would create. thanks for your good work and support awor !

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edited my post. first you have to make the dht receptors of these rats hypersensitive to dht. but its only an idea.

This isn’t necessarily true - lots of drugs treat/cure issues without completely understanding the root cause.

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You’re right, many drugs have been discovered by chance. Finasteride as a hair loss remedy, for example, was discovered by chance. But if you look at how drug discovery works these days for complex illnesses such as cancer, they are relentlessly investigating molecular pathways. I am not saying this is the only way. If you understood that, you’re misreading me. My point was when faced with a bunch of deregulated genes, we need to understand which ones are deregulated, so we can counter act. At the same time, someone might discover something that really works well, without understanding why it is doing so. That was my point about the baskets, we need multiple approaches, people working in various directions. Hopefully something will stick.

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I completely agree with you. That’s why the first step in a rat study of treatment protocols would be to try to induce PFS in rats. Nobody has even done that as far as I know so we have no idea what percent of rats would get PFS when withdrawn. This would be another valuable contribution of such a study. If the percentage is small, the second stage of the study would be a challenge. I suspect the percentage will be high enough though to allow testing of protocols on affected rats.

Otherwise, I agree with most of the other things you say. One thing to note is that epigenetic changes happen all the time in the body. It is not necessary to understand the exact change in order to reverse it experimentally. Anything that affects androgens has the potential to reverse the change. That’s why multiple protocols need to be tested - it will be like shooting in the dark but still in the right general direction. One potential treatment to be tested are corticosteroids which are known to reduce the sensitivity of androgen receptors.

I will try to write more in a couple of days.

I agree. A rat study would first need to test various ways of inducing PFS. One way would be to do exactly what you said. I suspect when “the right” protocol is found, a huge percent of rats, relatively speaking, will get PFS.

PS. That’s how I got PFS as well. I had taken fin for many years, then stopped for a number of months and then started again. That’s when it hit me.

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How exactly would you expect them to test for PFS if there hasn’t even been scientific classifications built around the pathogenisis of PFS, or defining the exact symptoms. Outside of this community and it being socially recognized to some degree, there are no official standards out there, especially in the scientific community, that list out how PFS is attributed. Do you classify mental symptoms as PFS? Sexual? Physical? All of the above? Where is the line drawn. If there were, our doctors wouldn’t be clueless to our condition. Melcangi’s studies are important for this reason. Until this happens, PFS will continue to only be a mere nomenclature to describe a very muddy and large set of withdrawl side effects that we have in common. How do you test for this?

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Very Well said brother

You test for sexual function in rats, for which there are established assays. Tests for depression, neurosteroids etc will be useful too but are secondary. If we can’t agree on the definition and characterization of PFS, I am more than willing to call the subject of the study “post finasteride sexual dysfunction”.

P.S. Melcangi’s studies are important. Everything is important. But the question should always be - what is the most important thing that should be done right now.

Donated to the foundation! I’m happy to support Melcangi’s work and any other studies the Foundation is proposing.

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What think Melcangi… will not like you.

3 posts were split to a new topic: Christmas 2018 fundraiser

Any Updates on his studies ?
Im wondering if Melcangi has already started study phase III. I think the phase IV will be more interesting for us anyway

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