Phase III and IV coming from Melcangi/Fundraiser

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WINTER FUNDRAISING DRIVE

New Research Afoot at the University of Milano

Dec. 14, 2018

Dear Friends:

We’ll start with the good news. Then onto the great news.

That’s right. We’ve got great news on the PFS fundraising front.

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As you’re no doubt aware, Roberto Cosimo Melcangi and his team at the University of Milano’s Department of Pharmacological and Biomolecular Sciences have been making steady progress in their investigation of PFS at the molecular level, aimed at determining the root causes of the condition while hopefully setting the stage for the development of effective therapies.

In July 2017, Prof. Melcangi published Phase I of his research, a paper in The Journal of Steroid Biochemistry and Molecular Biology titled Neuroactive steroid levels and psychiatric and andrological features in post-finasteride patients.

According to that study, PFS patients suffer from altered levels of critical brain-function regulators, including neuroactive steroids. The research also uncovered evidence of neuropathy of the pudendal nerve among those with severe erectile dysfunction.

Nineteen months later, this time in partnership with Cajal Institute and Carlos III Health Institute, both in Madrid, Prof. Melcangi, published Phase II of his research, a paper in Psychoneuroendocrinology titled Treatment of male rats with finasteride, an inhibitor of 5alpha-reductase enzyme, induces long-lasting effects on depressive-like behavior, hippocampal neurogenesis, neuroinflammation and gut microbiota composition.

“Finasteride treatment causes several alterations in the hippocampus,” the section of the brain responsible for processing long-term memory and emotional responses, the study demonstrated.

It also showed evidence of (i) long-term depressive-like behavior, (ii) alterations in neurogenesis, gliosis and increased levels of inflammatory cytokines in the hippocampus, and (iii) alterations in the composition of gut microbiota that was present one month after withdrawal of subchronic treatment of young male rats with finasteride.

The good news is, Prof. Melcangi has already designed Phase III of his research: a clinical study aimed at furthering scientific knowledge of the role that gut-microbiota alterations play in PFS.

The great news is, that study is already funded, with patient testing scheduled to begin this winter.

Two months ago, the parents of a PFS patient approached us to ask how they could help speed along Prof. Melcangi’s progress. Long story short: within two weeks they’d cut a check for Phase III.

Now for more good news.

Prof. Melcangi has concurrently designed Phase IV of his research, which will involve neurotransmitter signaling, neuroactive steroid levels and epigenetic changes in 5alpha-reductase.

And this is where you come in.

Our funding drive for Phase IV officially gets under way January 1, but we want to jump-start it immediately. Because this time the goal is $40,000, which we hope to raise in full by March 31.

So as the holiday season gets into full swing, please give generously to help keep Team Melcangi’s momentum going strong in 2019.

Donate now.

Thank you.

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Gut Bacteria Test?
#2

Thanks for posting @holyhead that’s great news. The parents that donated for phase 3 in one go as well. What amazing people. I shall definitely contribute to phase 4 funding.

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#3

As smart as Melcangi is, he is currently on a wild goose chase. There is plenty of literature that supports that AR dysregulation and androgen ablation induces gut microbiota changes and altered neurosteroid levels. This isn’t new information, nor is it the cause of Post Finasteride Syndrome or any other enzyme inhibitor issue.

Just can’t believe he’s spending that much on analyzing the gut microbiota when he failed to cite last year’s important study in Nature,

https://www.nature.com/articles/s41391-018-0061-x

which is very prestigious, identifying such changes in many non 5ari disruptions of the androgen pathway. In his previous studies, he just kept hypothesising about 5ar.

Hundreds of men have taken the gut microbiota approach, raising androgens, and using pure DHT approach. As we have seen, many times it has little to no effect, and even an adverse effect on the opposite side of tbe spectrum. This is evidence, albeit weak, that there is altered hormone signaling.

Another PFS study found that PFS patients had twice the AR expression than controls. And if we look at animal models with AR over expression and human prostate cancer models, androgen receptor overexpression creates a null hormone signaling phenomenon and even a toxic gain of function. This is what we are seeing with many of PFS patients. It is all over the forums. It makes perfect sense that people would be experiencing hypogonadism symtoms, alterations in skin, gut, and mental symptoms… To be investigating downstream things, at most you are simply creating awareness.

While myself and many others think the main issue is with receptor/hormone signaling, I hope these studies are able to raise awareness about persistent side effects in the predisposed from hormone inhibition. I personally won’t be contributing to this, especially after I have seen what he has said about saw palmetto and other inhibitors. Our money can be vested somewhere else.

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#4

Yeah you may be right who knows…All I have heard is wild theories from every side…Read my blog talk about crazy side effects…

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#5

I really don’t understand people on this forum. People are always moaning that nothing gets done and why don’t scientists fix the problem. As soon we make progress with anything scientific we love to criticise and deride. Prof Melcangi is a leading scientist who is focussing his research on pfs, and there aren’t many other scientists out there doing this. Let’s give him a chance. Again $40,000 is a small amount that this forum can easily raise in 3 months. Let’s support research and beat pfs. Of course if you know better than a leading professor with more than 30 years experience and the entire pfs foundation then please keep buying snake oil treatments instead!!!

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#6

The biggest problem is we really really don’t know for sure
pro melcangi seems to be less secretive about his findings and their seems to be more in the way of regular updates compared to Baylor

Above all it’s great to see that more awareness is being created and that professional people are looking into things to help us it sure beats our armchair scientists theories that’s for sure.

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#7

I did say at most it will raise awareness, which is nice. But it could be much much nicer.

I am also against at trying experimental treatments because in my experience every single thing has made me worse, permanently. So your inclusion of snake oil in your post was a little wild.

Once again, I am sorry- I knew people wouldn’t like that post but I am not going to hold back exactly how I feel about very important matters. I would rather see $40k go to a study looking at hormone signaling and focusing on over expression and what predisposes & or causes it. I wish Melcangi would focus on that. Everything he is looking at has been proven to be modulated by the Androgen Receptor.

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#8

It’s your money and you can spend it how you like, but why put other people off from donating. Do you even donate anyway to any other projects. I can imagine that Merck is against this research as well.

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#9

Any professional help at all is fantastic news
If guys like pro Melcangi are willing to put their time and reputation on the line to help us they deserve a huge round of applause and our up most respect and gratitude. The reality is You just never know who’s on the right track and if things are being covered from different angles that’s actually more advantageous than everyone going in one direction as it maybe the wrong direction this would be a catastrophic waste of funds and time.

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#10

No I don’t, I stated this on SolvePFS, so I don’t expect you to know.

I have just began working as I’ve started a career in nursing within the last 1.5 months. I also owe a cumulative 110k to various banks and agencies for student loans. I said I would initiate donation funds as soon as I was settled in financially which would take a few months. Axolotl would vouch for me as he knows my personal situation

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#11

Ok I apologise and I don’t know your situation. Your post just made me extremely angry. I’m normally a nice guy.

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#12

I would best guess after my improvements on clomid, trt to a point then Baking soda that it is a signaling issue…Damage to nervous system? An epigentic type of down regulation of the signalling mechanisim??

There was a great post here years back from an up and coming science student detailing the effects of finasteride on the spinal cord, brain and how that system affects everything in our bodies…Where is the studies on the brain and spinal tissue in Texas of those who participated in the Baylor study and then committed suicide later and donated their brains etc for study?? Also look at other Merck shit drugs and those that have been crippled and their autonomic nervous system destroyed by Guardsail vaccine…

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#13

I also didn’t sway anyone for donating. I stated I wouldn’t be and my reason for that. If melcangi had a PhaseV looking at hormone signaling, gene activation, epigenetic alterations to androgen receptor that would be god send. The foundation should be should be swaying him this way.

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#14

Break it up break it up
Shake hands guys
It’s good news all round it doesn’t matter which way you look at things or what our beliefs are
It’s all a giant step in the right direction

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#15

I am sorry but I disagree. Fair enough you don’t want to donate but it sounds like you won’t be happy until nobody donates and the study fails. Maybe you should discuss your concerns with the foundation directly

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#16

I didn’t take you to being rude… you’re entitled to your opinion as well. My goal isn’t for people to dislike me or create turmoil. I see your point about awareness and we have a PhD on our side. I hope you see my point as well. Perhaps we could all collectively write him to initiate a Phase V for what I suggested?

Baz there’s nothing to shake about or break up. At least I thought.

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#17

I think this is fantastic news and I will absolutely be making a donation as soon as I can. Thank to you the people who took the time and effort in putting all of this together. I am eternally grateful.

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#18

I’m just trying to get you guys to see things from both sides .
It all great news

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#19

everyone please donate generously, ever bit counts and this is our only real chance of improving our lives

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#20

Changed my post, see above.

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