Topical JAK inhibitors definitely work for androgenic aloipecia -- Big Development

[Tracksterderm]

Again little boys like you who are led solely by emotions. It's pure fear what you have inside, that's why you are blinded by hope. I have seen so many guys like you. They never turned out to be right and they eventually vanished probably in desperation. They would be so extremely sure of their case. It's no different this time mate. Evidence lacks again and there is much hype for nothing. It's a never ending cycle. I can even give you some links, it's pure comedy. Look at my post history on BTH.

False hope is a bad thing brah. This is false hope. Come back when you have anything to show outside of mice models, some evidence in humans you know? Before that you stand nowhere.

So I'll ask you again; EVIDENCE IN HUMANS?!?!?!?! Pictures? Data? Case report?

I want this to work just as well as anyone, but getting hyped up for nothing is f*cking nonsense. It has happened many times before and I still only see finasteride and minoxidil, no? It's tiring, a thing you might understand in a few years from now.

@swoop I think you sound quite knowledgable in your comments, and you always link to different studies to make the arguments. But hopefully you are wrong about this one.
As long as they still haven't tried topical JAK for Androgenetic Alopecia, then there is hope it will work.
It sounds amazing to me that they haven't tried it out by now, considering these are approved drugs and with Christianos comment that it would be very quickly established whether this works or not.

Now that there is financial backing, we should learn the answer within 2016/2017 (which goes for a number of other potential treatments as well).

 

[mr_robot]

For those wanting to go the IL-6 blocking route it's easy enough, all-trans retinoic acid (retin-a) and menthol both supress IL-6 receptors (http://www.ncbi.nlm.nih.gov/pubmed/2033252).

No need to wait for JAK inhibitors, I use both in my regimen.

 

[NorwoodGuardian]

For those wanting to go the IL-6 blocking route it's easy enough, all-trans retinoic acid (retin-a) and menthol both supress IL-6 receptors (http://www.ncbi.nlm.nih.gov/pubmed/2033252).

No need to wait for JAK inhibitors, I use both in my regimen.

Any result?

 

[mr_robot]

Any result?

Yes but I do not use them by themselves so I cant give you a scientific answer. I initially used minoxidil & pantostin with nothing in the way of regrowth after 5 months of use. I then added Retin-A, Peppermint Oil and Stemoxydine and got a major boost around the temples. Peppermint Oil is mainly menthol and I now use menthol crystals directly. Results could be due to IL-6 or simply that menthol is a penatration enhancer that is helping everything along. It is known that Retin-A helps minoxidil, that could also be due to IL-6R but again without a proper lab study there is no way of knowing.

 

[hellouser]

Yes but I do not use them by themselves so I cant give you a scientific answer. I initially used minoxidil & pantostin with nothing in the way of regrowth after 5 months of use. I then added Retin-A, Peppermint Oil and Stemoxydine and got a major boost around the temples. Peppermint Oil is mainly menthol and I now use menthol crystals directly. Results could be due to IL-6 or simply that menthol is a penatration enhancer that is helping everything along. It is known that Retin-A helps minoxidil, that could also be due to IL-6R but again without a proper lab study there is no way of knowing.

This isn't topical though.

 

[mr_robot]

This isn't topical though.

You could always drink menthol.

 

[papa pinrel]

Hey guys, when we could have this treatment available? years?
thanks you

 

[NewUser]

It's possible that JAK inhibitors do more than affect the immune system.

Yeah they do. Says so in the research paper published last October.

Meanwhile none of "the big three" are considered cures for any type of hair loss, androgenic or otherwise.

For example, statins lower cholesterol so people say the benefits of statins are due to lower cholesterol ... but statins actually do a lot in the body other than lower cholesterol.

They think statins and metformin could be the first real anti-aging drugs. The studies are ongoing.

 

[InBeforeTheCure]

Out of context.

He simply refers to the data from Christiano et al. that was performed on a rodent model, and refers to the interesting aspect of it (topical vs systemic). Immediately after he speaks of vitiligo and actual case reports (humans).

His phrasing is extremely awkward and misleading if he's not referring to Androgenetic Alopecia, but at the same time I don't see how they could possibly know about efficacy of topical vs. oral JAK inhibitors in Androgenetic Alopecia yet. Something doesn't make sense here. Has Christiano been doing shady back alley trials or something?

It's possible that JAK inhibitors do more than affect the immune system.

The most interesting thing about JAK inhibitors is that they could be able to alleviate SASP effects on nearby cells (including stem cells) by interfering with cytokine signaling. There is some interest in the JAK-STAT pathway in anti-aging research because of this, but to what extent JAK inhibitors can reverse Androgenetic Alopecia, if at all, I have no idea.

 

[hellouser]

Hey guys, when we could have this treatment available? years?
thanks you

First we need to wait 3 years to start mouse studies. Then we have to wait for case studies on women and children, then burn patients, then Phase 1, 2 and 3 trials... and then alopecia areata testing, universalis, totalis........ and only after all that is complete, will they start mouse studies to see if it works for men and then Phase 1, 2 and 3 trials for men with male pattern baldness.

The disrespect is real.

 

[whatevr]

First we need to wait 3 years to start mouse studies. Then we have to wait for case studies on women and children, then burn patients, then Phase 1, 2 and 3 trials... and then alopecia areata testing, universalis, totalis........ and only after all that is complete, will they start mouse studies to see if it works for men and then Phase 1, 2 and 3 trials for men with male pattern baldness.

The disrespect is real.

You forgot that they also have to develop the special topical formulation for Androgenetic Alopecia so add 2 years.

Btw Hellouser is your status stable with RU and CB and all that? Does all that stuff together actually do anything? I can't take finasteride anymore so I will have to jump on RU most likely. Gonna use your instruction thread for guidance.

 

[Swoop]

His phrasing is extremely awkward and misleading if he's not referring to Androgenetic Alopecia, but at the same time I don't see how they could possibly know about efficacy of topical vs. oral JAK inhibitors in Androgenetic Alopecia yet. Something doesn't make sense here. Has Christiano been doing shady back alley trials or something? \

Awkward indeed . I'll believe it when I see it. Initially I thought it might actually modulate the hair follicle to some extent just like immunomodulatory compounds like tacromilus or cyclosporine but even that is for me unlikely at this point. I haven't read about any occurrence of hypertrichosis or hair related changes whatsoever with any JAK inhibitor whether it was topical or oral. This is totally contrary to a compound like cyclosporine which can and actually quite often does induce hypertrichosis;

[FONT=&amp]The study group included 63 males and 17 females. The age of the patients ranges from youngest 18 years to oldest 62 years, mean age was 38.6 years. The study was conducted for a period of 2 years. All these patients were on standard immunosuppression with Cyclosporine, Azathioprine, and Prednisolone. All of them received Cyclosporine at a dose of 7 mg/kg/day at induction, which was tapered to a dose of 3 mg/kg/day, based on clinical status as well as blood level of the drug. The dermatological manifestations were assessed periodically. These patients were followed up for median period of 22.4 months. Hypertrichosis was seen in 56 males (88%). All the 17 female patients (100%) developed hypertrichosis. It disappeared in all after stopping Cyclosporine - in around 3 to 7 months. Hypertrichosis was the primary indication for stopping Cyclosporine in 15 (23.8%) of them.[/FONT]

Pure observations here, no hypothetical talk. Time will tell I guess.

Btw in relation to SASP this study might interest you; http://www.ncbi.nlm.nih.gov/pubmed/22404905

[FONT=&amp]Both corticosterone and the related glucocorticoid cortisol decreased the production and secretion of selected SASP components, including several pro-inflammatory cytokines[/FONT]

[FONT=&amp]Here, we demonstrate that two glucocorticoids produced by the adrenal gland – cortisol, the primary glucocorticoid used by humans, and corticosterone, used primarily by rodents but produced as a steroidogenic intermediate in humans, can decrease the production and secretion of selected components of the SASP, including the pro-inflammatory prototypical SASP component IL-6. Repression of IL-6 production was due in large measure to the ability of the glucocorticoids to downregulate two important pathways that regulate the SASP: IL-1α signaling and NF-κB transcriptional activity. Our findings validate the feasibility of screening for novel and selective SASP modulators, and identify the GR as a new regulator of the phenotype.[/FONT]

 

[papa pinrel]

First we need to wait 3 years to start mouse studies. Then we have to wait for case studies on women and children, then burn patients, then Phase 1, 2 and 3 trials... and then alopecia areata testing, universalis, totalis........ and only after all that is complete, will they start mouse studies to see if it works for men and then Phase 1, 2 and 3 trials for men with male pattern baldness.

The disrespect is real.

Wow then dont ndertand the hype in forums and why is peopple speaking so much about this, we have Histogen follica and replicel soon, a potential treatment which be launched in years is nothing new i think.

 

[Swoop]

First we need to wait 3 years to start mouse studies. Then we have to wait for case studies on women and children, then burn patients, then Phase 1, 2 and 3 trials... and then alopecia areata testing, universalis, totalis........ and only after all that is complete, will they start mouse studies to see if it works for men and then Phase 1, 2 and 3 trials for men with male pattern baldness.

The disrespect is real.

https://clinicaltrials.gov/ct2/show/NCT02001181

https://clinicaltrials.gov/ct2/show/NCT01831466

Completed trials for a topical JAK inhibitor.. Androgenetic Alopecia nowhere to be seen? Ridiculous right.. What a clown fiesta.

 

[hellouser]

Wow then dont ndertand the hype in forums and why is peopple speaking so much about this, we have Histogen follica and replicel soon, a potential treatment which be launched in years is nothing new i think.

I was being facetious. However, male pattern baldness is almost always overlooked. So it's not far from the truth.

 

[distracted]

Because Cotsarelis seems to agree with me; http://edition.cnn.com/2014/06/20/health/baldness-cure-alopecia/



Nah joke, that would be a bad reason.

I have several reasons but the following would be probably the most important one. When you go to this study; http://advances.sciencemag.org/content/1/9/e1500973.full



They probably refer with that to this study; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362521/

Which says;



It's likely that they refer to the AA mice model in this case.. Because in this case indeed, a topical formulation showed superiority over systemic treatment in AA mice model. As we can indeed also read from the supplemental material;



It wasn't much slower btw..

But let's assume they actually refer to actual humans that have tried oral formulations (actually published) and topical formulations (not published anywhere) of a JAK inhibitor for AA, from which they found that the oral resulted in more "robust" hair growth.

Well have you looked at actual case reports of people that found success for AA with a JAK inhibitor like tofactinib? Or even the ruxolitinib case reports in the last link?

Look at one example here which I posted recently on this link; https://www.instagram.com/thealopeciaexperiment/

Or at the case report of that guy in the first link where Cotsarelis talks. How can hair growth be more "robust" than that? In both cases it's pretty much rapid complete reversal lol.... So that wouldn't make sense would it. Besides let's assume that indeed they have seen more rapid hair growth in AA on humans with a topical formulation. Then what does it matter? At best it would maybe be a tiny bit faster, but eventually it's about the end result. Complete reversal of in this case AA, as displayed in these case reports.

Now the thing is that drugs have biological activity towards a target right? Finasteride primarily has activity towards the 5ar2 enzyme, and also towards 5ar1 at higher dosages. Just like JAK inhibitors have biological activity towards the JAK enzymes.

Now let's take a look at AA;




To simplify it in AA, "killer" T cells attack the epithelial compartment of the hair follicle. They hang around the bulb of the hair follicle. So what do JAK inhibitors do? Well they disrupt this process by latching onto these enzymes (which you can see in the above picture). By doing this they disrupt this process which leads to a decrease in these T cells and now the hair follicle is freed to produce a hair shaft again.

The funny thing is.... These killer T cells are around the close proximity of the hair follicle bulb right? So explain to me how these JAK inhibitors can overthrow these JAK enzymes in these T cells in AA (as evidenced by oral AA test subjects) but wouldn't for example on any other cell type in the hair follicle itself? That would be a laughable thing to assume.. And indeed as evidenced in the picture above you see that the picture illustrates that the compound latches towards the enzymes in the follicular ephitelial cells. The same could be said for every cell pretty much of the hair follicle...

Also remember oral JAK inhibitors do not work for Androgenetic Alopecia at the same dosages, period.

All in all there is really no evidence to believe this will do much at all. I'll eat my shoe if this will work and I obviously hope that it will work. But I'll believe it when I'll see it. Not going to get excited from a useless sh*t mice model. Even when you look at that mice model, SAG initiated hair growth just as about as fast as tofactinib so... There would be more, but I'll leave it at this if you don't mind :mrgreen:.

Thank you! Makes sense. Lol the people over at HLC2020 are acting like this is the cure. I think they're overly optimistic over there, but we'll see.

 

[Swoop]

Thank you! Makes sense. Lol the people over at HLC2020 are acting like this is the cure. I think they're overly optimistic over there, but we'll see.

To finish it my last post;

[video=youtube;6tPCqF0NmYE]https://www.youtube.com/watch?v=6tPCqF0NmYE[/video]

She says; "Last year we were working on a treatment of alopecia areata using JAK inhibitors in mice and we noticed quite to our surprise when we used the drug topically the mice grew their hair much more quickly, much thicker and much darker than when received systemically which gave us the first clue really that these drugs might be doing something to influence the hair cycle directly and not just influencing the immune cells".

So, yes she refers to that 2014 study which was on the AA mice model... But yeah in actual humans with AA we see the contrary, it's robust as hell and onset of hair growth is quick as hell. Doesn't really correlate at all with the AA mice model does it.

Btw mind everyone that JAK inhibition couldn't initiate anagen entry even in the normal mice model in early telogen;

[FONT=&amp]This finding implies that JAK inhibition cannot override the quiescence-promoting microenvironment at the early stages of telogen ([/FONT]9[FONT=&amp], [/FONT]10[FONT=&amp]) but is sufficient to promote hair growth at a later stage in telogen.[/FONT]

Now we just need to wait on human evidence/data, and hope that it does something really.

 

[whatevr]

BTW Swoop, I may be wrong about this, and if I am, then never mind, but I believe you said at some point about CB that will never match the effectiveness of 5-AR inhibitors. Or that might've been about Setipiprant. Either way... why wouldn't something like CB (or anything else that completely blocks the androgen receptor) be equally effective (if not more, actually, since it would prevent ALL androgens from binding to it) than Finasteride?
Provided that DHT only works at the androgen receptors and no where else.

So far it seems that based on effectiveness RU is worse than Finasteride, and CB even worse than RU, and it doesn't sound right.

 

[Oh Yea?]

BTW Swoop, I may be wrong about this, and if I am, then never mind, but I believe you said at some point about CB that will never match the effectiveness of 5-AR inhibitors. Or that might've been about Setipiprant. Either way... why wouldn't something like CB (or anything else that completely blocks the androgen receptor) be equally effective (if not more, actually, since it would prevent ALL androgens from binding to it) than Finasteride?
Provided that DHT only works at the androgen receptors and no where else.

So far it seems that based on effectiveness RU is worse than Finasteride, and CB even worse than RU, and it doesn't sound right.

Maybe finasteride has some sort of anti Inflammatory properties that the others don't..it does shrink the prostate. Inflamed prostate + finasteride equals less inflammation on the prostate.

 

[whatevr]

But that's because reducing DHT reduces the inflammation, no? I am not aware of any other kind of anti-inflammatory effect of finasteride being documented anywhere.
The only other thing that finasteride has going for it is an increase in estrogen (good for hair, bad for everything else), and testosterone (neutral at best, also bad for hair at worst).