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 (RC Melcangi)

Science
#1

Hello,

I’m not sure if this has been posted but Melcangi’s study’s transcript has been released (the one we helped fund). It can be found here:

http://sci-hub.tw/https://doi.org/10.1016/j.psyneuen.2018.09.021

I don’t think there’s anything groundbreaking here but perhaps someone who’s more into the science can highlight anything meaningful.

On an unrelated note, sage-217 is up on clinicaltrials.gov! They’re aiming to complete Phase 3 by November 2019. Coupled with their priority review status, a PDUFA date end of 2020 seems likely. Study can be found here: https://www.clinicaltrials.gov/ct2/show/NCT03672175?term=sage-217&rank=4

Thanks guys, be well.

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Possible Epigenetic Changes in PFS Patients is Focus of New Clinical Study at University of Milano
Sage Therapeutics Clinical trial of SAGE-217 (Zuranolone)
Finasteride induces in male rats long-lasting effects on depressive-like behavior, hippocampal neurogenesis, neuroinflammation and gut microbiota composition
#2

Anyone else having trouble with the first link?

#3

Both links work for me.

#4

Correct link to Melcangi rat study: https://www.psyneuen-journal.com/article/S0306-4530(18)30506-7/fulltext

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#5

Another step forward!

#6

I believe this link has the full manuscript. It’s a lot of what we already knew, but I think the stuff about the gut microbiota is very interesting…
https://sci-hub.tw/10.1016/j.psyneuen.2018.09.021

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#7

This study is helpful in expanding the body of knowledge with regard to the effects Fin-treatment has in the brain (e.g. neurogenesis, neuroinflammation) and establishes effects on the microbiota composition of the gut. All this exists one month after discontinuation of Fin. What this study does not seem to do is to identify why these effects are permanent even after discontinuation of Fin. I understood from the study announcement that possible epigenetic changes of the 5-alpha reductase enzyme would also be analysed. Maybe this will be done in a separate paper.

While I understand that the effects of Fin treatment have to be evaluated to establish the vast symptoms that we suffer from, these effects are all downstream. From a treatment perspective it makes more sense to explore the ultmate cause(s) that lead to these effects. I guess this will be part of the Baylor study.

I am a complete layman when it comes to biology. So take everything I write in this post with a grain of salt. Maybe people who are better versed in biology can explain the study results in the context of what we already know and need to know as well as the underlying strategy.

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#8

Isn’t this the study in which they were supposedly going to try treatments on rats? I was expecting more from this. I was at my mid 20s when I got PFS, now I’m nearing 40. I guess at least I can finally decide to get an implant if, once published, Baylor study doesn’t lead to a treatment either.

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#9

I agree, I was also expecting more.

#10

Yes, he’d indicated he’d found functional changes to the 5ar enzyme in PFS patients that are not mentioned in this paper so I’d expect there’s another on the way. Notable microbiota changes have already been established as occurring in patients after interruption of the androgen pathway with antiandrogen treatment so there’s nothing that consequential here. Still, it’s another paper suggesting biological consequences of finasteride on affected systems and flagging PFS as a thing. Of course, there’s limited scope to really gain that much of use to us from this method as treating a mammal with Finasteride is not modelling PFS.

Methylation: What is it?
#11

So, there is not really anything new in this study. Too bad. I guess every publication helps to establish a credible body of knowledge and quantity is certainly a part of it. I also understand that from a scientist’s perspective it’s a comparatively easy study to make with predictable results that increases their publication index. Hopefully, future publications are more substantial, though.

PastUser, who initiated community funding for Melcangi on Solve, has indicated in the other forum that there are more publications from Melcangi to come. So, hopefully, the functional changes to the 5ar enzyme will be addressed there.

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#12

3 important things from this study:

  • Gut microbiota is affected at the finasteride withdrawal
  • The levels of TNF-α at the end of the treatment with finasteride are largely increased.
  • A significant increase of the gene expression of this cytokine was observed after withdrawal.
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#13

I think getting a rat model of PFS is very hard thing.
PFS is very rare disease and only minor people getting
PFS. Same to mammal.
Anyway… We have to wait another study(Baylor) or more publications from Milano.
Baylor investigated about 5 years and delayed again, again. I hope They can find very significant things in PFS!

#14

@KoreanGuy Agreed.

This is the closest I have seen to an animal model of PFS, which only shows detrimental effects of AR overexpression, and only in muscle tissues: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2084330/

@Northern_Star Thanks for the info on future studies from Melcagni and cohorts!

#15

It says phase 2 research is complete but what about all the claims of epi-genetic changes to the function of the enzyme?? We already know how to prevent the condition it says…Yeah, don’t take the damn stuff…

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#16

Phase 1, 2 is completed. But it’s not a epigenetic results. Maybe Phase 3 study contains epigenetic results? I don’t know exactly yet but they say about
epigentic study. so they will publish about epigenetic
in near future.

#17

Phase 3 has not even been funded to my knowledge and we helped fund this study on solvepfs…Or would not have happened…And they already said he had discovered this is one reason we all raised the money we were pitched this line about the significant changes of the enzyme and he may have discovered the root cause…

#18

Possible Epigenetic Changes in PFS Patients Is Focus of New Clinical Study

SOMERSET, N.J., Jan. 29, 2018 – The Post-Finasteride Syndrome Foundation today announced Phase II of the clinical research on post-finasteride syndrome (PFS) being conducted at the University of Milano.

Led by Roberto Cosimo Melcangi, Ph.D., head of the Neuroendocrinology Unit in the Department of Pharmacological and Biomolecular Sciences, the new study will evaluate:

—In PFS patients: possible epigenetic changes in the 5-alpha reductase enzyme.

—In an animal model of PFS: behavioral parameters, and alterations in neurogenesis, neuroinflammation and neurotransmitter pathways involved in the control of sexual function, as well as possible epigenetic changes in 5alpha-reductase. Possible changes of the gut microbiota composition will also be considered.

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#19

I don’t get it.
Is that study 2 addressing possible epigenetic change of 5ar or not?
If not, wtf?

I am convinced there is not just an epigenetic change, it might be a mutation.

5ar has also important metabolites.

#20

Anyway, We have to wait another study and make monthly donation.
This is the only thing we can do for find a root.
Thanks to Milano and baylor about studying.
Keep going please!

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