JAK-STAT Signaling Jump Starts the Hair Cycle

Over the past few years, I have discussed the janus kinase signal transducer and activator of transcription (JAK-STAT) signaling pathway a number of times.  It has become of increasing importance in the hair loss world ever since JAK inhibitors were first shown to cure alopecia areata (AA) in 2014.  Even prior to that development, there had always been some interest in the JAK-STAT signaling pathway and its relationship to the hair follicle cycle.

However, since 2014, research in this area seems to have multiplied significantly.  In 2015, I discussed Dr. Angela Christiano, Dr. Claire Higgins et al’s groundbreaking paper titled “Pharmacologic inhibition of JAK-STAT signaling promotes hair growth“.

Now, in the latest (November 2016) issue of Journal of Investigative Dermatology, Columbia University’s Dr. Angela Christiano, Dr. Etienne Wang and Dr. Sivan Harel have published a new paper titled “JAK-STAT signaling jump starts the hair cycle“.  Thanks to the commentator in the last post who notified us about this.

However, it should be noted that this paper does not pertain to any new study or research by Dr. Christiano!  Instead, it is largely an analysis by the Columbia University team of a study/paper that was published earlier this year by Dr. Julien Legrand and his team at The University of Queensland.  This study from Australia was titled “STAT5 activation in the dermal papilla Is important for hair follicle growth phase Induction“.  The conclusion of that paper was that “STAT5 activation acts as a mesenchymal switch to trigger natural anagen entry in postdevelopmental hair follicle cycling“.  STAT5 is an acronym for signal transducer and activator of transcription 5.

Dr. Christiano’s team raises some interesting points in their analysis, especially the fact that while Dr. Legrand’s research has shown that JAK/STAT5 signaling in the dermal papilla is required for anagen onset in the murine (mice) hair cycle, other researchers have shown that JAK inhibition is able to induce the transition of telogen to anagen in wild-type mice.  This contradiction highlights the complexity  and still yet to be fully understood nature of JAK-STAT signaling in the various stem cell niches of the hair follicle.

Dr. Christiano continues to believe that topical JAK inhibitors could work to treat regular male pattern hair loss via the following quotes:

“Targeting the JAK-STAT pathway might be a potential treatment for nonimmune alopecias”.

“Further work in this exciting area may uncover novel pathways that control hair follicle stem cell quiescence and activation.  Targeting
these pathways pharmacologically may facilitate the discovery of new therapies to treat various forms of alopecia”.

“In our recent study (Note: its the one I mentioned earlier from 2015) we found that in wild-type mice, topical application (rather than systemic treatment) with JAK inhibitors was required to trigger the telogen-to-anagen transition, possibly due to a requirement for high threshold local concentrations of the drug in the hair follicle.  Further, we found that the timing of topical treatment was crucial: treatment induced hair growth only if administered after 8.5 weeks, during late telogen“.

Nothing groundbreaking in this development, but it seems like the University of Queensland based Australian team of researchers is important enough to warrant inclusion in my global map of hair loss research centers.  One of the co-authors (Dr. Kiarash Khosrotehrani) of their paper specifically mentions research interest in “hair follicle biology, cycling and regeneration” in his biography page.

FYI:  For the scientists amongst you that are interested, there is another paper in this same November 2016 issue of Journal of Investigative Dermatology titled: “Effects of Imiquimod on Hair Follicle Stem Cells and Hair Cycle Progression.”

98 thoughts on “JAK-STAT Signaling Jump Starts the Hair Cycle”

  1. Study jak in AA 2015
    Confirmation in human 2016
    Treatment in the market 2017/2018?

    Study of jak on aga 2017?
    Confirmation in humans 2018?
    Treatment in the market 2019/2020?

    My conclution if work in aga ( i dont believe) will be before 3 or 4 years since we se the drog for AA in the pharmacy.

  2. I have some hope on Follica and Histogen.
    I’m also skeptical about Thorn Medical Company but at the same time I believe they could surprise us. I don’t understand how a reputable company can make such claim if it’s not true. I don’t understand why people are not talking more about them.

    Anyway, about JAK… I have mixed feelings about it. I don’t understand how it’s taking so long for them to just inject it on the scalp of people with AGA. I mean, how can it be so hard? Sometimes I wish I was a mouse hahah

  3. Wasn’t there a strong connection between Follica and Aclaris several blog posts back? Perhaps Follica will use Jak as part of the topical home treatment after in- office wounding procedure?

  4. Twice daily I’ve been taking a spoonful of Tone’s turmeric (has Curcumin in it, which is a known JAK/STAT disturber), a pinch of black pepper which has piperine (causing it to not immediately be taken up by the liver…. aka makes it stay bio-available), and olive oil (makes it instantly fat soluble). I’ve been doing this for a month. I swear to god, that growth of my hair has at minimum equaled that of minoxidil. It hasn’t brought any old ones back to life as far as I can tell, but what i do have (body hair, fingernails, eyebrows included) are growing noticeably faster. There is something to this JAK/STAT thing and hair growth.

    1. That’s why taking photos in your bathroom are so important. You can swear you see more hair but the question is if the camera will see the same.

    2. >Twice daily I’ve been taking a spoonful of Tone’s turmeric (has Curcumin in it, which is a known JAK/STAT disturber), a pinch of black pepper which has piperine (causing it to not immediately be taken up by the liver…. aka makes it stay bio-available), and olive oil (makes it instantly fat soluble).

      That’s gotta taste amazing /s

    3. For JAKi’s to work (to trigger follicles to enter their growth phase), they have to be topically applied; even ultra-high potency pharmaceutical JAKi’s don’t do anything for AGA when taken orally/systemically. IIRC Curcumin has some minor DHT-inhibitory effect, so that could explain any perceived changes in hair growth.

  5. Admin and Other Knowledgable Individuals:

    I am a female Ph.D student suffering from female pattern hair loss (FPHL). My background is not in the biological sciences; however, from my own research, it appears that many of the major players (i.e. RepliCel, Riken, etc) who plan on utilizing stem cell research are operating under the assumption that hair loss suffers have a “donor zone.” This, of course, is widely not the case for women with FPHL. FPHL is characterized by diffuse thinning, with concentrated hair loss on the top of the scalp. In other words, the occipital scalp–the area from which cells are meant to be obtained in stem cell treatment–is not immune from the hair loss/miniaturization in women. I would imagine that stem cell research is a cure limited to men w/AGA. Yet, I see Replicel, for example, claim that its treatment can be used to treat women with AGA as well.

    I’ve contacted the CEO of RepliCel. He offered to explain whether/how the treatment should be effective for women, but when I attempted to schedule a Skype meeting with him, he stopped responding to my messages.

    Does anyone have any thoughts on this? Is it possible that these stem cell treatments might be effective for women?

    Hopefully Yours,
    Kate

    1. Many males also have diffuse thinning on the whole crown and sides. I believe if you at least have 100 hairs on your head which with FPHL you should keep a good chunk of your sides which would be your donor zone… it should work for you maybe even better than on a males. That is my opinion anyway.

    2. Hey Kate,

      I’m a girl with AGA as well and have always had the same questions you do.

      I’ve lost a ton of hair from the back of my head and I don’t think these hairs are any more resistant than the rest of my scalp.
      I think it could help regrow the follicles but you’d have to keep getting treatments so they don’t become dormant again.

      Anyway, I don’t have my hopes too high for Replicel anyway. They used to answer all my emails, which I love, but the results of the trials were far from great. Histogen seemed to have had better results.

      I’m more hopeful for JAK inhibitors, Follica and Histogen and none use the same technique Replicel does.

    3. I think Female pattern baldness is kinda similar to mpb. Both of them are susceptible in the crown area. The stlyings are different so it kinda looks different . Woman part their hair in the middle or side and their hair are long , but if they have a hair cut like man it will kinda look similar. Woman also has a donor zone . The crown area is more vulnerable than the occipital area regardless of sex. I saw many elderly woman with hairloss having dense hair in the occipital zone. So dont be depressed. Stay strong and lets pray to god.

  6. Admin, excellent topic. Fingers crossed as always… I’m still stuck at 50/50 chance with these jaks!

    Also, 5th paragraph… there’s a “there” instead of “their”

  7. New update on the Samumed website:

    October 25, 2016
    Samumed Successfully Completes a Phase II Androgenetic Alopecia (“AGA”) Biopsy Trial Studying Regeneration of Hair Follicles
    San Diego, CA – Samumed, LLC successfully completed a 135-day study of its topical compound, SM04554,on49malesubjectswithAGAanalyzedbybiopsyofthescalppriortoandpostdosing. The safety and the efficacy results of this second Phase II Trial further support the safety and efficacy findings from the company’s prior trials. Moreover, the biopsy results support the program’s mechanism-of-action regarding new hair follicle regeneration.
    As the Company previously reported, efficacy data from its first Phase II AGA trial showed statistically significant increases for both objective outcome measures: non‐vellus hair count (a primary outcome measure) and hair density (a secondary outcome measure), using the pre‐specified statistical model. Further, in that first Phase II AGA study, there were no serious adverse events observed in any treated patient, and the incidence of adverse events was similar between treatment and vehicle groups.
    The Phase II AGA Biopsy study results will be presented at upcoming medical conferences.

    1. “Moreover, the biopsy results support the program’s mechanism-of-action regarding new hair follicle regeneration.”

      I think this is new? I never heard Samumed and neogenesis mentioned in the same sentence before.

      1. Very weird usage of words… re-generation does not sound like neo-genesis.

        If you regenerate an old almost lost hair-follicle, it’s not neo-genesis.

  8. Thank you Admin!

    I am South Korean suffering from AGA. I often visit your blog and get some great information. I really hope there be a cure before 2020…

  9. Thanks for sharing the Samumed news, Anonymous. It gives a lot of hope. They’re confirming hair follicle regeneration. To what extent remains to be seen. You made my day.

  10. Regarding their last sentence: The Phase II AGA Biopsy study results will be presented at upcoming medical conferences.

    In a previous communication by Samumed they states they are going to present at the Forbes Healthcare summit from 30 nov. – 1 dec.

    This is just an assumption, but there is a chance they will present the details of this phase II at this conference.

  11. Nice find on SM anonymous! Fingers crossed it’s 10x better than Rogaine.

    As for JAK the findings seem promising but I wish they would just test this stuff on aga already so we can either keep it on the list of potential treatments or scratch it off. All these press releases and papers are getting annoying since they don’t say if it works or not.

  12. Yeah I don’t understand why it is taking so long to determine whether or not it works on mpb if it kickstarts the anagen phase as quickly as they say, and as quickly as it regrows a full head of hair lost to AA. Not saying they are obligated to tell us anything at all, but everytime I see some new article on Jak it is about how it MAY be useful for mpb. But by now I am almost positive they know if it works or not. Would be nice to know either way. Either its something to look forward to or its not, and it would be nice to stop wondering about it.

  13. Great news on Samumed Anonymous. Thanks for sharing.

    For the people hoping it will be better than minox/fin:

    If they release this product, I can almost garuantee it will be better. Their initial findings point to both complete stop of hairloss progression as well as increase in hair count. They’ve stated that phase 2 has upheld and reproduced these findings.

    I think it’s just about safe to say that if things continue to go as planned for Samumed, then it will be a pretty safe bet to be better than Minox/Fin.

  14. I hope SM can zip through a phase 3 as quickly as they did with phase 2. And get this product out for us to use. SM and Follica will be the only two treatments that will be released in the US if things go well. Everything else is in Japan or mexico.

    1. @Mjones not sure how you feel about Fidia, but their treatment will also be available through their US branch within 2 years (sounds like it will be released in 2017).

      1. I’m not too confident about Fidia. Sounds like a lot of hype and turning out to be a let down. They focused on AA first which is a bad sign. If they had a mpb treatment they would have shown some pics and started with that first on their trials. I hope I’m wrong though.

        1. I’m not completely sold on Fidia either, and would like them to release some sort of data (doesn’t necessarily have to be pictures) soon, which it sounds like they might do after their trials are over in December.

          They didn’t start with AA first though. Dr Brotzu was using his lotion on MPB patients dating back a couple of years now. The reason there has only been talk and photos of AA recently is because Brotzu himself is spreading that info because he is still in control of the AA trials. Fidia itself is currently only working on the MPB side of the lotion.

  15. Any idea what the differences are between a dormant AA follicle and a dormant AGA follicle? I think I remember reading somewhere that an AGA follicle can eventually be reabsorbed into the skin. However the framework (stem cells) remain to regrow a new one if activated. Seems to me that (topical) JAK inhibitors will work as long as a follicle is present so it is able to be pushed into a growth phase. Maybe that’s why Dr. Christiono started the other company that’s focusing on the cell culturing method.
    Culture the cells necessary to reactivate long lost follicles in slick bald areas.. JAK inhibitors to help them along plus restore still active ones. Using both methods in tandem might make a lot of sense.

    1. New update on the Samumed

      Samumed Successfully Completes a Phase II Androgenetic Alopecia…… Regeneration of Hair Follicles…. successfully…….completed….results of this second Phase II……support the safety and efficacy findings from……..prior trials……
      follicle regeneration.
      …….previously reporte………first Phase II …….showed statistically significant increases ………Further, in that first Phase II AGA study, …….was similar between treatment and vehicle groups.

      The Phase II AGA Biopsy study results will be presented at upcoming medical conferences.

      Só they will show the seme thing….. 1 mora time.

      1. …Further, in that first Phase II AGA study, …….was similar between treatment and vehicle groups.

        Does this mean that they are getting the same results as the AA study?

      2. Hey maybe it is just me but……… when……. you…… write…… like……… this…… I …….. can’t…… follow…. what…. you……. are……….trying…….to…….. say.

    1. Yeh i definitely grew all my hair back. And then as soon as it was full and thick again it started thinning again. Its like fin/minox only work for a certain amount of time and then get less and less effective. For me anyway.. but i must say 12months after starting fin and 6 months after starting minox my hair was all back with no recession. And now i have this frizzy jew fro. Still a nw2 though

  16. Sd it breaks down cots follica procedure. Im disheartened by the number of years he has been researching hairloss and has only come up with this device and the same old fat wrinkle face insomnia bags under eyes minoxidil solution. Stick a fork in me. Aga is a beast.

    1. Yup they stopped Tweeting for a while, but are now back and favorited a couple of my older Follica related Tweets yesterday.

  17. @tom, please stop spreading false information! Its getting f***ing tedious…If you know something that the rest of us dont regarding Follica and their compounds (which you claim is minoxidil) please explain and post links! Follica has never stated that the compound they mention is minoxidil…

    1. It’s not minox guys. Watch the good morning America interview with cots from 2008. They said undisclosed new topical formula. If it was minox we all would have found data and links regarding it. Just wait and see and stop speculating.

  18. Methods for treating baldness and promoting hair growth 
    EP 2648676 A1 (text from WO2012078649A1) 

    Guys im saying this for two reasons:
    First its on the timeline or whatever on hot website, which has been very reliable so far
    second, if you do a search on the follow in you will see cots invention and look at how much it mentions minoxidil, especially towars the end. It seems the only other competition in the article is latanprost however I doubt that will be used because it was never put through mpb fda trials. Feel free to to logically critique my insight. I really hope im wrong guys. Against:

  19. For people who really want to maximize their chance of new hair growth and especially people who want to maintain, i feel like the best things you can do is fin, minoxidil mixed with a retinoid (my choice is 0.5%retinol), derma roller, shampoo with peppermint and alternate with a ketaconazole shampoo, and take amino acids L-Cysteine, L-Methionine, and L-Lysine . Make sure your hair is not too dry from the minox so use either an organic conditioner with natural preservatives or a natural moisture spray. I like activance. IT contains rhodanine and Msm. All of this will cost about 350$ per month. I would prefer a hair transplant i just dont have the money.

    1. I feel like libido for males has something to do with it also. When i firstly started taking an ssri i had no libido and no hairloss? If i take viagra i lose incredible amounts of hair.. ? Blood flow maybe? No idea

  20. resume:
    Jak: NO
    replicel/shiseido/histogen: poor results and delays, delays, delays

    real cure and hope: riken/kyocera: 2018 trials and 2020 market.
    beyond 2020: printed hair
    patience , the solution is near 😉

  21. what about Brotzu?
    i saw the full interview with the doctor and he is claiming that brotzu lotion have good results for people between 20-30.
    Some people says brotzu is gonna be in the market in 2017
    what do u think guys?

  22. What i dont inderstand is why the pharmaceutical companies have not changed the chemical structure of either finasteride or dutasteride to minimize sode effects. Or even minoxidil for that matter.. i know there is nanoxidil but is it much different? Sorry to talk about viagra again but when viagra was invented it wasnt made for a sexual disfunction reason.. although in trials they noticed that it had the side effect of a raging boner. So they sell it for that and they made cialis and another (cant remember the name) specifically for erectile disfunction. So why dont the pharmaceutical companies do the same thing with hair loss meds? Minox is still ised for blood pressure and hypertension patients. ANd finasteride/dutasteride is still used for enlarged prostate. Surely there would be a market for a more specific chemical geared towards hairloss

    1. Funny to read this since I got a fat transfer done to my cheeks (to correct some damage left from another procedure). I don’t see how it could help with hair but good to know they’re researching all the possibilities

  23. I have also Vitiligo (especially on my penis). It’s a auto-immune disease. Some people think there is a correlation between Vitiligo and Alopecia (Areata).

    http://patient.info/forums/discuss/vitiligo-and-hairloss-11947
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004208/

    But my hairloss does not look like alopecia areata…

    Also… Some people think there is a correlation between Prozac and Vitiligo…

    http://factmed.com/study-prozac-causing-VITILIGO.php
    http://www.ehealthme.com/ds/prozac/vitiligo/
    http://survivingantidepressants.org/index.php?/topic/2758-ssri-antidepressants-may-also-affect-human-immune-system/

    Prozac, Risperidone and Concerta (during 14 years at very high doses) is the reason of my total baldness (I lost 99,98% of my hair by diffuse ans extreme miniaturization on all the scalp… 100% soon 🙁 )… Vitiligo is also a reason? I don’t know.

    To be continued…

    1. End of AA trial done by brotzu will be next month, he’s expected to reveal results in a conference,
      most important is the AGA trial conducted by fidia, it will end in december, so expect news in Jan

      1. thanks hlscc!

        btw, the doctor Brotzu said that the product works already, right?

        So probaly we’re gonna have the product on the market at the begining of 2017 if everything goes fine (he said in the interview that the product work good and that there isnt a way to improve it)
        Fingers crossed!

    1. yes
      they sent to me this message:
      We are planning to offer treatments before clinics trials on a controlled basis by the end of 2017 or beginning of 2018, but only in the U.K.

  24. This study “Androgens modify Wnt agonists/antagonists expression balance in dermal papilla cells preventing hair follicle stem cell differentiation in androgenetic alopecia” looks very promising?!

    Particularly this part ” WNT10b overcame androgen inhibition of HFSC differentiation. ”

    Is this what samumed is working on do you suppose? Apologies if this is not of relevance here.

    http://www.sciencedirect.com/science/article/pii/S0303720716304294?via%3Dihub

  25. Mjones I want to know why you believe follica is not using minox? I know they tested a compound called lithium or something about a year a ago and it did nothing.

    1. I can’t say that I know for sure but I would think the topical would be something more advanced than Rogaine. Worst case that it ends up being Rogaine, I wouldn’t mind if it grew back tons of hair.

  26. Hi,

    I was browsing through this blog, and noted that most users were commenting passionately in favour of JAK being a potential cure for Male pattern baldness.

    Are there any news, or has the hype started to deflate?

    I’m 37 year old male who enarly lost all hair on the top, and would like to be updated on way or the other with regards to this possible cure.

    Thanks all.

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