Current situation studies-wise?

General Discussion
#1

Hey everyone, I haven’t been coming here because I try to ignore my PFS and just get by in life. However, it’s catching up to me and I don’t know how much longer I can last.

Can anyone tell me what we have to look forward to in terms of study results and anything else that might provide insights into what our problem is? I’m really at my limit now and feel like throwing in the towel.

What ever happened to the Baylor study? What other studies are coming? Is there anything else to look forward to? Any sense of what I might have to look forward to would be greatly appreciated.

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#2

The Baylor study is still ongoing. Not sure when results are expected. It’s been quite the slow burner. I think the last estimate from Awor was in October last year when he thought it would be published within the next 12-18 months. Today that would mean within the next six months. Given the history with delays of this study, let’s hope it comes any time next year. There is a lot of buzz that this study will be groundbreaking. Let’s hope all those years of waiting are worth it.

Melcangi recently published something, but it wasn’t groundbreaking. Rumour has it that further studies from his side are ongoing. The Italians are publishing a lot and quickly, so there will probably be something coming again in the next months. Rumour has it that they found a functional change of the 5ar enzym and that they are looking at epigenetic changes that may be responsible for that. Any discovery there would be very helpful.

Sage Therapeutics is making decent progress with Allopregnanolone analogues (an important neurosteroid that is significantly lowered in PFS patients). Phase 3 clinical trials are expected to commence at the end of this year. If these are successful there might actually be a medication that directly targets a proven deficiency in PFS patients.

Other than that, the communities of PFS, PSSD, PAS and other patient groups are increasingly joining forces which will hopefully increase the importance of our problem and will leverage resources.

Unfortunately, it’s not like a cure is around the corner. But I think we are getting stronger as a community, there are a lot of scientists aware of and interested in our probem, the Baylor study will hopefully be published soon and provide a breakthrough in the understanding of our problem, and if we get really fortunate, there might be medication on the way that may improve crucial PFS symptoms like depression and anxiety. Personally, I think this angle makes a lot of sense. I think it is worth waiting for the results of these trials.

I know it’s tough, but hang in there! And, if possible, help the Foundation with donations and participate in the community research project: (Link). We all need to help and do our part to get better!

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#3

Thanks for providing all this useful information. I very much appreciate. Didn’t know about Sage Therapeutics. Will check it out. In my case, it’s the sexual sides that have ruined my life. Do you know if there is a link somewhere where I could find a current list of all publications that have been produced so far? I might do a literature review.

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#4

The PFS Foundation has a list of relevant publications: Link

Personally, I think that the paper from Traish (“The post-finasteride syndrome: clinical manifestation of drug-induced epigenetics due to endocrine disruption”) provides a great overview.

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#5

Ok I’ll read that first. By the way, my problems actually started with Accutane. I did not take Propecia. But my symptoms are all the same. Do you have any sense of where post-Accutane research currently sits? Are they considered the same thing or perhaps is it further behind? I know people have hypothesized that the two have a lot in common, but has progress been made in actually establishing that yet? The post-accutane community seems to be much less organized. I guess because it’s mostly made up of teens rather than adults.

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#6

Accutane is a 5ar1 inhibitor, Finasteride is predominantly a 5ar2 inhibitor but also to a lesser extent a 5ar1 inhibitor. So it makes a lot of sense that Accutane and Finasteride can lead to the same symptoms, and that’s what we see across the communities. In fact, as the Traish paper referenced above points out, all endocrine disruptors can lead to the same set of symptoms. We see this with people “treated” with Finasteride, Accutane, anti-depressants and several other compounds. Across all these patient groups there is a subset of patients that develop these symptoms that we here call PFS. The mechanism behinds all this have yet to be established. But I think the picture is pretty clear to anyone, including support from a specialist like Traish.

Based on that there is an increased amount of cooperation between the communities. It does not make sense that we all fight the same war separately. I think it is fair to say that the PFS community is by far the most advanced with this forum, the PFS Foundation and an established network of scientists. I am not aware of anything like this for Accutane, for example, that’s why more and more Accutane patients come over to this community including some very bright people who are a great asset to our community. We here have a great plattform, but we don’t have the numbers. Together with Accutane and PSSD patients we can pool much more resources. And obviously, combined our communities present a much larger and thus important problem.

I think since the relaunch of this forum, there has been quite a spark in our community and in our collaboration with other communities. The community research project linked above is one of the results.

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#7

Northern_star did a pretty good summarizing everything.

I too am also optimistic about sage-217/allo analogs. Further, I think what Melcangi found: impairment of neurogenesis and inflammation in hippocampi are both direct causes of not having enough allopregnanolone.

Being able to treat the depression/anhedonia and anxiety would be a huge increase in the quality of life for many. Also, I don’t think it’s totally offside to speculate that having our emotional processes (less) dysregulated, we also revive some of our sex drive too.

I recommend that you sign up for the investors newsletter on Sage Therapeutic’s website. You can also follow their Phase 3 MDD study on clinicaltrials.gov (estimated end date of November 2019)!

Be well.

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#9

I think most people are waiting to hear a cure for the sexual side as it has a major impact on a mans life nobody is going to appreciate being left in a situation where they have to rely on medication to induce errections and for some people it can be even worse as the medication doesn’t work for everyone.

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#10

I hate what finasteride has done to us all and it’s frustrating how long its taking to get some answers as to why these side effects have persisted to the point where I can’t help but feel we are condemned to a lifetime of paying the price of taking this drug.

#11

I tried signing up for a couple investor email items, though I didn’t see anything exactly called a newsletter. Anyway, good to be clued in on their existence and looking forward to finding out more.

Could you give me a rough idea what it is that they might possibly be able to provide? Are we talking about perhaps 3 years from now a drug might become available that I would go to the doctor and have administered to me once a month or something? Will it be something incredibly expensive? I suppose it probably will at least initially. Any additional idea of what it is exactly that they will be able to provide would be greatly appreciated. When I reviewed the literature a couple years ago indeed Allopregnanolone was the hormone that really stood out to me and it was a source of great frustration that there was no apparent way to treat a deficiency in it.

#12

Sorry, perhaps a newsletter was the wrong term to use. You can sign up for email alerts which will give you an auto email for any events and/or presentations that Sage announces. There’s things like quarterly shareholder calls and other conferences where they give presentations - sometimes they give insight into their drug candidates. They will obviously announce data read outs of their trials too.

They’re providing an oral drug (sage-217) that is meant for once a day dosing. Whether you have to take the drug chronically or periodically is still to be clarified from your phase 3 study.

As far as dates, their final, pivotal trial is expected to be completed by November 2019. If the data read out is positive from that, Sage applies for a New Drug Application and then the FDA reviews that Application. If the FDA is satisfied with the trial, they allow for the drug to be prescribed to the general public.

So when would this drug actually be released to the general public? Well, Sage also has an IV (injection) drug very similar to sage-217 called Zulresso (which was formally known as Brexanolone or Sage-547). Zulresso is on the verge of acceptance from the FDA (the exact date is actually sometime in December of this year). All-in, it took Sage twelve months to go from Zulresso’s phase 3 completion to FDA’s acceptance. So using that estimate, we could estimate that Sage-217 would finish its phase 3 in November 2019 and then get clearance from the FDA around November 2020. I’d say we’re just over 2 years away from this.

Once it becomes available, it would be akin to being prescribed an anti-depressant. You go to the doctor, say you’re suffering from major depressive disorder, hint that you heard about sage-217 (which will renamed at some point), and you go pick up your prescription. In regards to cost, no one really has an idea. However, if you think of new anti-depressants when they came out like Zymbalta - maybe a couple hundred bucks a month if you don’t have coverage from work? I would highly doubt this would be cost prohibitive to the average person.

Correct, there has historically been no way to treat the deficiency directly. People will have a million theories of what went wrong and why we are in this mess but here’s my opinion: I agree that Melcangi’s study back in 2017 showing a ~300% reduction in Allo is very important. Melcangi’s most recent study showed lack of neurogenesis and increase in inflammation in the hippocampus - both as a result of the lack of Allo. Melcangi’s most recent study even showed that we have emotional impairment and long-term memory impairment likely from the changes from inflammation and lack of neurogenesis. Therefore, the cause of whatever you want to call it being from changes in the gut microbe, down regulation of 5ar, etc. If we can get some solid relief from now having Allo in our system, that would a huge increase in the qualify of life we live. I’m carefully optimistic.

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#13

Thanks for all this information. Do you think it will be possible for some of us to try Zulresso this December in order to preview the potential effect of Sage-217? I would do almost anything to obtain some possibility of relief of my current situation. In my case, the sexual disfunction (and concomitant elimination of ability to have intimate relationships or children) is the real killer. I can live with being depressed in itself, but the prospect of having to stand by and watch myself become too old to start a family (may already be the case), isolated, and purposeless, is unbearable. I guess what I am trying to say is that I suspect for many of us the situation feels quite urgent, with time running out, and I wonder what means might be available for people to go ahead and try possible new treatments early. Thanks again for keeping on top of things the way you have and sharing your knowledge.

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#14

No problem vkg1.

I understand the frustration. I’m not sure if this helps, but there have been several guys on this forum that went on to have functioning relationships and children despite the challenges.

Zulresso’s is only approved for postpartum depression and not for major depression. Very unlikely that you would get a prescription. Furthermore, it has to be delivered through an IV for 60 hours straight where, for the most part, will be administered in a hospital. Couple this that even if you were to somehow get this prescribed off-label, you’re not getting any insurance coverage. All of this make it very difficult, if not impossible to get a prescription, but also very cost prohibitive as well.

Unfortunately, the closest thing is sage-217. Two years may seem like a eternity but that day will come.

I know you didn’t ask for it, but I wanted to give some personal advice that I wish someone had told me back in 2016, when I got for PFS. Disclaimer that this is my own opinion:

a) limit your time/visits to the forums - the cure isn’t buried here. It’s useful to get periodic updates on say, trials, once every 3-4 months. I like to come by to post on study related matters when they are released or answer questions if they’re directed to me. But try not to do more than that or you’ll obsess over this condition which will do you no good. In fact, as helpful as this community can be, I think it’s a destructive habit if you visit often. From experience, a lot of nonsense gets posted about this tea extract being a cure or crap theories about viruses. It’s complete crap and you’ll drive yourself nuts trying to read it.

b) Develop a few hobbies: Again, I can understand the frustration that you may not be getting joy/satisfaction from doing these, but they’re a great time passer and this is what you need right now. For me, it’s weight training, squash, and golf (weather pending). I’ve even joined a couple leagues to make sure i’m getting regular exposure even when I’m not feeling up to it.

c) Keep working on your career/school: You’ll want to give up on this since you have no motivation or passion, I get there and still experience that. Despite that, there’s two benefits for sticking to it. One, it’s a great time passer in itself and makes those Monday-Fridays melt away. Two, for me, I’ve been very frugal since I don’t spend money on “fun” things since I don’t enjoy things. By doing this, I’ve saved considerable money that I do plan to enjoy when the time comes.

I hope you found this helpful.

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#15

Yes I agree with you that doing much more than checking in on the state of the science is generally counterproductive and that it’s best to concentrate oneself into the other areas of life. But with treatments very possibly finally on the horizon, there will be a stage where it’s time to switch gears and really try to pursue resolution. Thanks for all your advice. My personal worry is just that I don’t have those 2-3 years left of “fertility window”. Out of curiosity, do you understand how the Zulresso is supposed to work? I thought the idea was that it would effectively replace missing Allopregnenolone. How could receiving replacement Allopregnenolone for 60 hours have long-term effects?

#16

Out of curiosity is there any way to get Sage 217 medication or something that acts very similar right now? Legally or not, I’m just curious is there a way out there? I’d be very interested to try something along those lines and see what happens.

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#17

do we think that sage 217 can affect sexual symptoms? thanks

#18

I don’t know about you guys call me dumb but wouldn’t it be nice if things were explained much simpler when we read these studies alot of the terminology is somewhat alien to me.

#19

I know how you feel mate, your not dumb at all, your just new to this stuff and that’s perfectly normal. When I first learned about all this a couple of months ago I hadn’t a clue about anything scientific, I barely knew what genes did lol I was that bad with this stuff, never heard of the word epigenetic or methylation before this, but I got interested in reading more about different things and it makes a lot of sense now, I think you’ll definitely pick it up over time but at first it’s definitely very overwhelming if your not into science or biology which I wasn’t initially.
What helped me out was reading the conclusion part of the study’s that people publish, it gave me a short summary and was easier to pick up the terminology and get a gist of what they where discussing.

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#20

There is A similar drug called Ganaxolone that can be purchased as a research chemical.

Solvepfs had a discussion about it but I don’t think anyone tried it.

http://solvepfs.com/viewtopic.php?f=6&t=2379&p=35791&hilit=Sage+217#p35791

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#21

Anyone tried the above, very curious to see if this has an effect