I read through the forums and chats, sometimes I think they all so close related to their pfs routine, their neuroinflamation theories and their thousand ways with the red light helmet into the recovery, that they really don’t want a goal oriented research with a chance to identify the root case.
See this is absolutely terrifying to me because the body is infinitely complex as it is and we took something they put out and we may never know what the implications are
Now neurosterpids which we know Fin fucks with also fucks with epigenetics???
Fuck You Merck
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I don’t know if it it’s completely wrong what Melcangi wants to do…
I mean, we are suffering and looking for a cure suitable for everyone and I agree with you but time keeps going on and we don’t know how long it takes to find this cure.
Melcangi is true to say that he doesn’t have find something could cure everything but he just wants to help us and give us an opportunity to bring our lifes to a decent baseline.
We can go either more deeply in the understanding of our epigenetics modifications and haveing at the same time a life better than now ( at least just a little bit more). I don’t know why are you so angry with him?
I remember that in the beginning he was completely alone to study our cases and now maybe it’s close to give us finally a cure?
There are many guys that are suffering and maybe they don’t have time to wait until the right and specific cure would discovered ( maybe in 10 years or more)
Are you going to wait for other 10 years or maybe you should live your life right now?
This is not a critic but I think the truth is the middle. maybe I’m saying something wrong
If I put in the effort to conduct a study of this magnitude with any integrity I’d make sure it sounded more legit than those management trainee seminars where they sell you a book for $95.
I realize we’re desperate but anyone hyped over this announcement needs their bullshit detector calibrated. There is nothing of substance in the email and that isn’t an accident.
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It certainly wasn’t helped by its presentation i.e. what I just told you was a lie etc.
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Nobody’s angry with anyone. We’ve been asked for our view on the study’s merits by multiple people so we gave it.
This type of thinking has been going on in the PFS community since the 2000’s - two decades ago. What people fail to grasp is that due to the limited fundraising capacity of our community, every time we chase short-term solutions, we delay the science which is going to deliver us meaningful insights about the pathomechanism(s) driving PFS. That information is essential to identify possible therapeutic targets. And while we chase that short-term solution, no progress is being made towards the long-term solution, meaning it’s still just as far away as it was before.
At some point we as a community have to accept that this isn’t a quick fix, because until we do, it’s only going to take longer to solve.
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Thousand theories, thousand protocols, thousand recoveriers discussed from invisible, anonymous guys in the dark corner of the internet. Millions of money spent for special pfs doctors, recovery specialists products and self medication. All the research on finasteride effects without looking for the root case of it all. No one showing up his face for decades.
Once Merck Organon takes it from the market and we’ll drift down the river like a ship of forgotten fools in the Middle Ages praying the benefit of hcg to the end of our days. Like we did two decades.
Now there is the chance for a break through in awarness and research and we have to force all the money goal oriented.
If the pfs community donated the money for selfmedication and pfs specialists only one year, we should have hundreds of thousands of dollars to find a treatment.
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I agree with you … which is the next step we are looking for?
What is it going with Bayer’s reaserch? Is it started?
I just want to say that Prof. Melcangi is objectively the only person who has been dealing with PFS for about 10 years, producing tangible results.
I think that before expressing opinions of this kind, and before drawing conclusions about his work, one must at least be as qualified as he is.
In any case, everyone allocates their money wherever he wants, but the team of the university of Milan has been working for over a year on a possible cure for PFS, represented by the neurosteroid allopregnanolone. And here too, there are already promising results: soon there will be the first publication about it.
That’s not true, given Prof. Khera has published what are the most significant findings about PFS thus far.
Why do we need to be scientists to observe that after 10 years of work, Prof. Melcangi’s work still doesn’t acknowledge the many physical symptoms being reported by patients? Why can’t we comment that his work isn’t grounded in the clinical reality? It doesn’t take being an academic to make that observation.
This is the same type of irresponsible framing that was used in last week’s announcement. It’s totally irresponsible to suggest that this group is working on a cure, or even a treatment, when we have no information about the pathomechanism involved and therefore no therapeutic target. This is literally the same type of trial and error patients perform on themselves. Dysregulated neurosteroids are a symptom, not a driving mechanism, so therefore this is simply trialling a substance to potentially treat a symptom, not a cure. There’s a record of a patient trialling brexanolone already on this forum which was unsuccessful.
This just simply isn’t the way science works.
At the end of the day, we have nothing against Prof. Melcangi’s group personally. We’ve publicly thanked him for his previous work, which has massively helped progress understanding and awareness of the situation facing patients. But we’ve made it abundantly clear above why we cannot further support his work.
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Is pfs just the switch in the brain easy curable by straightening of the hormonal axis (The Andrological, Neurogenetical “Melcangi approach” in my eyes) or a severe epigenetic dysregulation of 3800 genes all over (different) body and brain (tissues) being worth to find the root case (The Baylor / Kiel Study approach)?
Just my thoughts as an ExMicroBiologist about the recent discussion. I’m not postulating a theory, I’m not a know-it-all either or even claim to know something better than an experienced scientist
The swittch in the brain theory and how easy could be a cure than by simply straightening of the hormonal axis (The Melcangi approach)
In many discussions among those affected, the androgen receptor is seen as a kind of docking point in the pituitary gland tissue, which no longer works after finasteride treatment and releases too few neurosteroids and hormones. Then the pfs “experts” inject HCG (or use a thousand other hormones, protocols and supplements) and the defective switch is thrown again and you feel recovered by straightening of the hormonal axis. Now many hope to find exactly this switch, i.e. the genes that flip this switch in the brain and heal it with gene editing.
The AR Overexpression theory (The Baylor / Kiel Study approach)
The (active) androgen receptor (DHT Complex) docks in all “male” cells at the DNA promotor region and ensures that “male” genes are amplified in the “male” tissues (penis, testicles) or amplified in others (muscles). This means that the andogen receptor that connects to DHT in the cytoplasm and is thus activated is found in all cells and tissues that are responsible for the male expression. From the hair follicles, through the brain, to the sexual organs, to the skin and muscles on the feet. And a small percentage of million men who use finasteride are predisposed to develope pfs by an epigenetic problem to regulate down AR expression after quitting finasteride.
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Thank you my friend for translating this scientific jibber jabber into language for the common man. I appreciate that you have raised yourself out of that depressed morass to write these posts. Please continue, my aged friend. There is hope for us yet. Jim
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Why do you say this? I don’t agree that his work is grounded in clinical reality, especially since he’s done direct empirical research on the CSF of PFS patients and found some very strong impt regarding undetectable levels of neurosteroids in the patient group.
I understand that there is competition for funding for studies and the forum has an interest in promoting its own projects but I don’t agree with the way Melcangi’s research has been characterized on this forum.
I think this is incorrect as well and there’s a very good chance that inhibition neurosteroid production created conditions for PFS to emerge in a small group of patients. A lot of statements have been made as fact that are speculative here without any caveats.
Even if neurosteroid inhibition was a primary cause of PFS, and there may be multiple, simple replacement of brexanolone would be unlikely to reverse PFS. But as far as I know, brexanolone has only been trialed by a single patient on here who received a questionable specimen so I don’t think that could be properly ruled out. Neurosteroid impairment could make the brain especially vulnerable to injury from many different kinds of stressors which could lead to many other forms of downstream dysregulation with many circularities and feedback loops which are very common in neuroendocrinology.
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Can you elaborate on what you are saying here? Certain things are sometimes confidential so I appreciate that it may not be possible to elaborate but it is common on this forum for people to make speculative claims as factual without being supported by evidence. A lot of assumptions are being made about Melcangi’s work it seems and I’m trying to get a sense for what is confirmed and what is not.
Melcangi has been over 1 year trying to characterize the experimental animal model following the administration of finasteride and then allopregnanolone. He currently has several data available from that experiment, and is analyzing them. What is certain is that allopregnanolone has multiple effects on PFS, such as its protective role, on low-grade gut inflammation. And on this and more the first research will be published soon.
The announcement of the PFS Foundation, concerning the 50k $, for the University of Milan, serves precisely to allow the Melcangi Team to continue the experiment.
Personally I don’t really believe that there are people who have really taken allopregnonolone for PFS, because: 1) it is not possible to take it (unless you are pregnant), 2) it is only administered in the hospital and the costs are very high
Prof. Melcangi’s goal is precisely this: to prove with preclinical experiments that treatment can help people with PFS. Only with these data in hand will it be possible to convince a hospital committee for an off-label trial.
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a doctor here took allo. he sourced Sage using his doctor credentials under research purposes from a lab
ended up getting negative effects from it
I think it is a stretch to say that Melcangi is working on a cure but I do agree that finasteride’s disactivating effects on allo’s neuroprotective properties very likely plays a large role in the pathomechanism of developing PFS, at least for many patients. He’s still doing fundamental research which I think means that he might not reach a cure or treatment in the near future but the research that his lab has done and the work of Marco Bortolato are really on the cutting edge.
Epigenetic research too is at the cutting edge but my sense is that epigenetic dysregulation of genes likely comes as a consequence of a traumatic injury caused by finasteride’s neuroprotective depletion.
I understand why it’s being done but I think it is disappointing that the official position of PH is negative on Melcangi’s research when I think all these approaches are complementary. I don’t think many of the criticisms are fair or accurate which is why I felt it was important to opine.
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Well it is unfortunate that your sense isn’t really a useful tool to gauge what is true and what isn’t. And you might want to get it recalibrated since people have been banging their heads on objects since the dawn of human civilization, yet there’s no recorded cases of people’s penises disintegrating as a result of this.
There’s nothing to be disappointed about. There is no need to make the focus of research any more broad than it needs to be, and that is all Melcangi’s work has been. Broad. Without any real insight since that study demonstrating a deficiency in neurosteroids. I do not consider any research on patient’s gut microbiota to be useful insight.
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Your post didn’t make any sense, just filled with dogmatic opinion and no logic or justification. Its a huge problem on this forum.
there is a lot of substance to the Melcangi research but you clearly haven’t spent the time or effort to look into much.
For the record though, by traumatic injury i did not mean physical impact. there are a million different things that can cause adverse neuronal changes. Any kind of stress (immune, mental, social etc) can cause changes. Finasteride blocks neurosteroid production as a primary effect of the drug (by 5-AR inhibition) and it can make patients vulnerable to all different kinds of neurological and physiological harm. the fact that certain neurosteroid levels were undetectable in the CSF of every patient tested is a very strong clue. Because finasteride directly impacts neurosteroid production, it is a very strong sign that it is involved in pathomechanism of the disease if they were persistently depleted in every sample tested.
i think you guys taking at face value everything you hear. I personally trust more a university experiment, leaded from researchers, insead of “doctor”.
Which allo did he take? He has been in hospital for 3 days as pregnant woman? Did he convice Sage to give him 30$k treatment for post partum depression for his PFS ? 