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 ? 
Melcangi also did a study on the 5-AR gene in CSF of PFS patients and found that 56% of the patient group had altered epigenetic methylation compared to control group of 8%. Highly significant results and it shows something impt it is only present in 1/2 of the PFS group so it begs a lot of questions. Epigenetic modification is most definitely involved in PFS but it isn’t the same for all patients so there needs to be a more unifying cause. It is notable that all patients showed impaired neurosteroid levels.
It isn’t clear what this current Melcangi study is about and there’s such a large bias here that people are rejecting the work without having relevant info and just making assumptions about it.
Nice straw man argument. Your claim is that epigenetic modifications can’t be a unifying cause simply because the modifications were heterogenous for that one gene. Claim doesn’t hold up since there are 1000s of genes. Why aren’t you looking at the study that looked at AR overexpression and found that it was present in all patients that were studied? Is that not notable for some reason? Or that Baylor’s analysis found widespread epigenetic dysregulation?
For the record, you are alarmingly lacking in self awareness.
Cool. Don’t think there are any reported cases of people having their penises disintegrate as a result of adverse neuronal changes caused by immune, mental or social stress.
that’s not what a straw man argument is. But there are many many things that can cause epigenetic changes so even if you assume that there is a universal and precise epigenetic change in all PFS patients then you need to figure out how that epigenetic change was created in the first place. Neurosteroid impairment combined with some kind of other catalyst can definitely explain that and makes a lot of sense when combined with many other circumstantial factors and evidence. they are also very clearly implicated in sexual functionality so yes, there is a very strong reason to believe that neurosteroid disturbances would be responsible for the main symptom seen in PFS (but many others too).
you’re still misunderstanding what I’m saying though. there are obviously many complexities involved in PFS or it wouldn’t have continued to be a mystery for decades. there could be an infinite number of stress factors in combination with the neurosteroid depletion that result in structural damage. there is a reason that PFS happens in a minority of patients that take PFS and obviously taking finasteride would have to be a necessary component to developing PFS. the interaction is what you are misunderstanding.
You are right - it is not a strawman argument. I have my logical fallacies mixed up because I am constantly seeing them on this forum.
No matter what way you spin it, the biggest issue with considering neurosteroid impairment as the root cause of this issue is that it does not explain how androgenic dependent issue literally disintegrates in some patients. Why consider an answer that can’t explain all the symptoms patients are experiencing, when there is an answer that does?
The jump from all of the negative effects of neurosteroid depletion to having androgen dependent tissue disintegrating is a huge one. I’d be willing to consider the possibility (and honestly inclined to, because it would make solving this problem a lot easier), but I don’t see how it’s possible to make that jump.
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I’m not sure exactly what you mean by ‘androgen dependent tissue disintegration’. But I would consider posing your question to Dr. Melcangi before assuming that the explanation does not exist.
Epigenetic modifications are a really hot new topic in biology and nearly everything will cause epigenetic modifications. Psychological stress or PtSD will cause epigenetic changes. I do think it is worth exploring PFS from every angle, obviously including epigenetic research, but I don’t think it makes sense to categorically reject neurosteroids other than competition for donations which I don’t even think is so practically relevant here. I think Melcangi’s studies will likely get funded without donations from the forum but I just don’t think it makes sense to categorically dismiss it.
Everything here is still largely in the exploratory phase and it will take a long time for the science to catch up here. I’ve been living with this for over a decade and have seen the pace at which things move so I’ve decided to focus on trying to bolster my health more holistically. I still have an interest in having the science get figured out though.
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university research initiatives get corrupted all the time.
literally happened to us
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Guys, if you want to donate to the study…donate to the study. It’s pretty simple. Nobody is stopping you.
I’m not sure what this circular discussion is achieving.
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Guys, what about the research in Kiel? What is the reason for the delay? I read about 3 researchers who can help us there - it’s a strong and young team.
Is it really hard for us to find 12 sick people in Europe?
No, I’m asking without pretension.It’s just discouraging.
There’s not really a delay as such, the process of organising a study just takes time. If we were able to use the samples collected by Baylor as originally planned, we’d be well underway by now, but given we had to find a clinician who could help us collect new samples, it’s meant the process has taken longer than we hoped.
Finding a clinician who is familiar with the disease, willing to participate, willing to be a publishing author, takes a lot of time in itself. There are very few of those, especially in Europe. Organising the logistics of how those samples will be collected at their facility takes time. Organising the logistics of how samples will be transported to the research facility, safely, and stored to avoid contamination, takes time. Writing clinical surveys in two languages and importantly, writing an ethics proposal in consultation with researchers, takes a lot of time.
We have the numbers we need for the study to go ahead and we’ve already selected the patients we think are most suitable. Now we’re just waiting for ethics approvals to go ahead before we can put wheels in motion.
Would we like for this to have happened faster? Of course. None of us want to delay research into this disease any longer. But we also needed to do things the right way, which unfortunately takes time.
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Did you let these people know they’re selected yet or no?
I cannot help but agree with Frustrated’s comments.
I personally believe it’s totally ok for PFS Network to refrain from funding Melcangi’s studies but I believe PFS Network should also stay away from making content related judgements with regards to Melcangi’s work. He’s one of the few actual scientists who’s been consistently putting out work towards understanding this disease and thereby also raising awareness.
We’re all trying to work towards the same goal here. When PFS Network is actually expressing dismissive comments with regards to Melcangi’s work or hypothesis I wonder whether PFS Network is aware of the large power they have in influencing the PFS community.
Expressing general support and actually financially supporting Melcangi’s work are two different things. I think a community as powerful as PFS Network should, aside from financially supporting, support Melcangi’s work in every way possible. No explanation is needed since people can choose themselves who they give money to.
This is a direct example why I think PFS Network should refrain from making medically related quotes like these. These statements can be very harmful because most PFS sufferers have no medical background and will interpret these statements coming from PFS Network as true. But we actually have no clue if this example is true. Finasteride caused a disruption of hormones in the first place so dysregulated neurosteroids could very well be a driving mechanism (and actually caused epigenetic changes after).
Just like we have no clue whether epigenetic changes are a driving mechanism. We have not a single clue like Howell/Khera actually state in their Conclusion of the epigentic changes publication, quote:
Given gene expression per se is not mechanistic and does not imply causality, experiments with downstream processes of protein expression and activity should be undertaken to provide mechanistic data and clarify the results of this work.
https://sci-hub.se/10.1016/j.jsxm.2021.05.009
As you know I highly value your commitment and work for our community Mitch. I do however think it’s extremely important we are able to discuss topics/concerns like these openly and freely.
PS I have been systemically financially supporting PFS Network with a monthly donation and am also considering financially supporting Melcangi’s work.
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is there a way the backend logistics can be prepared in advance while we wait for the approvals?
I appreciate that Professor has been consistently working to spread awareness but that does not exempt him from criticism (whether right or wrong).
we have limited resources in general, if something doesn’t seem right, id rather avoid hitting that pothole.
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