Rat study for testing protocols. Realistic or not?

pvdl · October 9, 2019, 5:53pm

What do you guys think of Sibelios idea/request?

I completely agree. That’s why I think we need to fund a rat study testing treatment protocols. This is the only way to know for sure what protocols work and what don’t. Even if nothing works, this by itself will still be extremely valuable information. The alternative where everybody is testing everything on their own - with a great personal expense and a great risk to their health - is ridiculous and will never result in a treatment protocol because it would lack statistical significance. People are spending thousands of dollars going to doctors, on supplements, on blood tests, on all sorts of sketchy treatments. All of these money are wasted as far as discovering a treatment goes. I have been meaning to write a long post explaining how I see such a study.

The first stage of the study will attempt to induce PFS (or rather, long-term sexual dysfunction - for those who are likely to argue that PFS has not been characterized and we need to spend another ten years defining the disorder) in rats testing various methods such as long-term exposure, then withdrawal, then re-exposure. The goal of that stage would be to determine the most common mechanism for getting PFS but also to establish a reliable method for producing a population of rats with PFS for subsequent trials.

The second stage of the trial, after a number of rats with PFS have been produced, would be to test treatment protocols. Depending on how many such rats are available, a different number of treatment protocols can be tested and compared to a control group. There are a lot of potential treatments to be tested - methyl steroids, DHEA, the cdnuts protocol (this would be important even if only so as to lay that protocol to rest once and for all), DHT, etc. Even if no cure is found, identification of temporary boosters would still be valuable.

Such a study will not cost a lot of money, relatively speaking, especially if done in a lower cost country. By any means, the cost of such a study will be vastly less than the combined amount of money everybody here spends on doctors and treatment protocols, and yet it will be a far more effective way (the only way!) of looking for treatments. It will also be vastly less than the amount other studies have cost.

Such a study needs to be the absolute highest priority of everyone suffering from PFS and of the Foundation. Other studies being talked about and sponsored, such as the Melcagni studies are not looking for treatments but rather are investigating the fundamental science behind PFS (going in the wrong direction, if you ask me) and such studies have a 20-year results horizon. (In fact, no study looking for treatments has ever been done.) This is an acceptable horizon for an academic researcher who has no sense of personal urgency and who’s incentives are entirely in producing theoretical knowledge. This horizon however is completely unacceptable for us, the victims of PFS who need immediate relief in order to survive, even if this relief is not complete or without clear understanding of its theoretical underpinnings.

It is in fact entirely possible to discover a treatment without understanding the underlying biological mechanisms involved. Most drugs are discovered before complete or in fact any understanding of why they work, beyond the superficial. We know that a PFS treatment most likely would affect the androgen system of hormones and the androgen receptor (AR). This is a good starting point. In other words, we would still be shooting in the dark but in a well-defined and specific direction.

There is a credible theory of PFS involving the upregulation of the AR involving epigenetic changes. Epigenetic changes are not that special and happen all the time in the human body and any factor or combination of environmental factors has the potential to completely or partially reverse the changes. There are a number of ways the AR could potentially be downregulated - including by raising DHT for a prolonged time, by methyl steroids which are proven to downregulated AR, etc. It is a simple matter of finally testing a number of such protocols.

Sibelio · October 9, 2019, 8:34pm

I would donate money earmarked specifically for such a study. I think if we have a concrete study design with a clear goal - i.e. first step, try to recreate PFS in rats - we will be able to raise a good amount of money.

Sawproblemo · October 9, 2019, 8:42pm

How much would the study cost?

Sibelio · October 9, 2019, 8:56pm

We could identify a couple of research groups who have done work with finasteride/dutasteride and rats and ask them if they would be willing to do such a study and how much it would cost.

Andrew35 · October 10, 2019, 8:38am

This idea is very positive but it was suggested back in Dec 18 so why hasn’t anything happened.

Melcangi might know if we can induce pfs in rats so it might be worth emailing him.

I have a theory that those with the worst neurological symptoms are the most creative or outgoing here. Why? I think creative people are able to access more of their prefrontal cortex. Therefore PFS is able to access more of their brain. This could be identified in future surveys. If I’m right then we have one group of patients who are more susceptible to PFS.

we could start a what’s app group if people want to get involved.

Why hasn’t the Foundation set up a rat study to test PFS protocols? Do they think it could work? Maybe someone could email them as the study may not be viable.

Mcbbould · October 10, 2019, 3:19am

How do you make sure the rats have PFS?

orthogs · October 10, 2019, 6:54am

Yes, that’s the main issue I suspect.

jinstewart · November 25, 2019, 7:21am

Might there just be a chance that what’s happened here happens in the rats?

By which I mean, say you manage to induce PFS in rats and can reliably test for it. You throw all the supposed cures at the rats in rat-doses and then none of them get cured. Then one of them gets cured with Tribulus, then you never replicate that again - no more rats are fixed from Tribulus. Then in a month repeating everything over and over Gingko cures another one, but doesn’t cure any others, and didn’t cure any before that one. Then one of your other rats from the first batch you didn’t euthanise just gets better where none of the others do, again even if you can even reliably diagnose PFS and PFS cured in a rat.

If I just took a massive dump on the idea I’m sorry for it. But it does seem like the same circle we’ve tried here before on (VERY willing) human guinea-pigs desperate to get back to where they were, who can reliably report symptoms too. We had Solvepfs and other forums… lots of protocols and nothing we could replicate reliably. Don’t we think it’d just be the same thing except more work in determining what a rat’s feeling?

(EDIT - also when I say above I am sorry then I do mean it, if I’m stomping on hopes there. I think (probably dangerously ofc) that human self-experimentation is the way, which I’ll carry on with I must say. I am certain given the many years of PFS that there’s not one-size cure for it. But where to look for a fix for the 2+ types of PFS then who knows. Where DO we start even? How you respond to masturbation? To increasing or reducing androgens? There’s not even one thing that PFS seems to be as far as I’ve read.)

orthogs · October 10, 2019, 9:00am

This is a possible eventuality. But it’s unlikely if the same weight-adjusted dosage is given. Who knows, it’s all speculation.

pvdl · October 10, 2019, 9:40am

The difference is that it’s a controlled environment and you can test 100s of rats potentially.

Can rats get PFS?
How can you reliably tell if a rat has PFS?
How many rats are needed to get a decent number of PFS rats? I. E. do you need potentially 1000s of rats for 10 PFS rats?
How different do rats react to humans when it comes to PFS and protocols?
How likely is it that one will find a cure? I. E. is shooting in the dark worth the investment, even if it’s a much more controlled environment than a forum.

jinstewart · October 10, 2019, 9:42am

Yes definitely makes sense on all.

I’d also add in the maddening confusion of some things which might cure one rat make another one worse. And also how you’d find out if a rat is feeling worse or not. But who knows, there might be something consistent. You’d definitely not run out of protocols to try!

orthogs · October 10, 2019, 10:46pm

It hasn’t happened so there’s little point discussing the hypothetical.

Sibelio · October 11, 2019, 12:16am

If I were a rat, researchers would be able to tell I have PFS very easily…

Andrew35 · October 13, 2019, 9:18pm

You throw the rats a piece of rope and the ones that try to hang themselves will likely have PFS. The rest will simply sit around watching.

If we knew which genes led to PFS that would be much easier. Melcangi identified one gene to do with Methylation.

There maybe some obvious signs if their DHT lowered assuming they have DHT.

At what point do we stop being victims of PFS and start doing something to take back our lives?

pvdl · October 13, 2019, 9:23pm

Lol.

pvdl · October 13, 2019, 10:19pm

Any moderators want to chime in? @Greek @Dubya_B @awor @axolotl @Northern_Star etc.

Sibelio · October 13, 2019, 10:46pm

And phase 0 of this study, of course, should be to directly establish (i.e. in a placebo controlled study) that PFS exists in the first place, which believe it or not, has not been done in animal studies so far, to my knowledge. It is as simple as giving 100 matched pairs of rats a single dose of finasteride vs. placebo and then counting how many in each condition permanently lost their sexual function. Has any study in history been easier and more straightforward than this?

Andrew35 · October 13, 2019, 11:27pm

Rat as an animal model for male erectile function evaluation in sexual medicine research.

Animal models have contributed, to a great extent, to our understanding and advancement in the field of sexual medicine. Many current medical and surgical therapies in sexual medicine are the direct result of the development of such animal models.

So we can determine if a rat gets ED from taking Propecia.

Sibelio · October 13, 2019, 11:53pm

Also, once you have rats with PFS it will be relatively simple to test the heck out of them to see what’s wrong with them. Unlike previous studies, you are only going to test rats with PFS, not the whole group who took finasteride, which is going to give a much more valid signal of the relevant abnormalities.

orthogs · October 14, 2019, 1:04am

I’m on-side @Sibelio. Why is this approach not being advocated by the foundation? It is extremely low cost and high reward.