Jefferies 2016 Healthcare Conference — Dr. Neal Walker Confirms that Topical JAK Inhibiters will be Tested (and Work!?) on Androgenic Alopecia Patients

Update: Listening to the webcast again (yes it is still available), Dr. Neal Walker clearly states that while systemic JAK inhibitors did not work for androgenetic alopecia, topical JAK inhibitors did work for androgenetic alopecia (and not just for alopecia areata)!  This is huge.  Thanks to commentator “Bob Ross’s Hair” for typing out the exact quote below for us:

We will be developing a topical JAK inhibitor for androgenetic alopecia, and the data on that is quite interesting in that they found that the systemic JAK inhibitor does not work for that particular indication, but the topical does, mainly as a function of the target being more superficial in the skin and not really accessible from a systemic circulation.


The important Jefferies 2016 Healthcare Conference is going on in New York City as I am writing this post.  It started five minutes ago (12pm EST — aka NYC — time).  The CEO of Aclaris Therapeutics, Dr. Neal Walker, is presenting.  You can view it live via registering here.  Or from here.

The best part is that 19 slides are already available to view at the top of the ongoing webcast, and Dr. Walker just mentioned that they are now more confident about JAK inhibiters and will be developing a topical version for androgenic alopecia!!  One more small leap for “nasa_rs”,  but will it finally translate into one giant leap for mankind?

Slide numbers 16 and 17 mention androgenic alopecia.  The key March 2016 acquisition of and partnership with Dr. Angela Christiano’s Vixen Pharmaceuticals (Columbia University IP) is what seems to have spurred the optimism behind developing and testing topical JAK inhibitors on androgenic alopecia patients.  Slide 16 also mentions that they are working on next generation JAK inhibitors called “covalently bound highly selective JAK3 inhibitors.”

Note that those slides and the audio webcast presentation are both supposed to soon be available on Aclaris’ website, but will only remain there for several weeks.

497 thoughts on “Jefferies 2016 Healthcare Conference — Dr. Neal Walker Confirms that Topical JAK Inhibiters will be Tested (and Work!?) on Androgenic Alopecia Patients”

  1. Hopefully NASArs and ADMIN will catch this… quite interesting. Others my find this interesting as well.

    I’ve already posted a bunch of stuff above (and on other write ups) about Stat3 and AGA etc… One specific thing I posted which I find very interesting is the roll of Stat3 in keratinocyte mitochondria. You can find that link near the top of this post. Hair shaft itself is made up of keratin. Lowering/eliminating this rescued some of the cells nuclear metabolic genes (genes from the nucleus of the cell… not mitochondrial genes), and rescued mitochondrial (main cellular energy source) function. One of these genes is NRF1 which interestingly is involved in cellular metabolism. We already think that obviously the hair follicle’s metabolism of more powerful androgenic hormones than testosterone is the primary difference in those with AGA and those without.

    https://en.wikipedia.org/wiki/NRF1

    Under “Biological Process” one of the things listed under this was “Organ regeneration” in regards to the NRF1 gene.

    Then I found this awesome write up:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773137/

    This is in neurons, not hair follicles, but is still very interesting. 12/15 Lipoxygenase targets neuronal cells MITOCHONDRIA under oxidative stress. We know oxidative stress is what is going on in androgenic follicles from the inability to properly metabolize androgenic hormones stronger than testosterone. This creates ROS. Furthermore, the article mentions 12/15 Lipoxygenase mitochondrial deregulation as being a factor in Parkinson’s disease, and there is a big link between premature AGA and risk of developing Parkinson’s disease later in life from a somewhat recent genetic study.

    Then I found this article:

    http://www.pubfacts.com/detail/24165129/1215-lipoxygenase-contributes-to-platelet-derived-growth-factor-induced-activation-of-signal-transdu

    12/15 Lipoxygenase contributes to PDGF activation of STAT3, and that 12/15 Lipoxygenases are crucial by-products of ROS (Reactive Oxygen Species ) something we know is rampant in AGA follicles because of their genetic inability to properly metabolize DHT. The article then talks about how genetic or pharmacological (medicine) interference with a 12/15 Lipoxygenase inhibitor prevented STAT3 phosphorylation.

    So why is this all interesting? Who remembers the Benoxaprofen articles that admin posted? It talked about the case studies of two men who had AGA and who took Benoxaprofen for other things and regrew hair in same density as before… Well the primary purpose of Benoxaprofen is as a LIPOXYGENASE INHIBITOR. So no ability to make Lipoxygenase means no ability to make Lipoxygenase 12/15 which means no ability of this pathway to respond to ROS and activate STAT3 via PGDF. You can wiki “Benoxaprofen” and find that info under “Toxicodynamics” and follow the link to the British Medical Journal if you wish. This is a big difference from other NSAID’s in that it directly targets single nuclear cells. Remember, this drug was only approved for a very short time before being pulled from the market because of deaths.

    Once again, you can tie another big link to STAT3 on this mystery.

  2. Something also random…

    http://blogs.plos.org/biologue/2015/06/16/understanding-images-micrornas-contribute-to-hair-loss-and-follicle-regression/

    I believe I’ve posted this one before, but wanted to add something to this. This talks about miRNA-22 being a key player in hair loss. It silences over 50 keratin distinct genes and that silencing of those genes is a prerequisite for actively growing follicles to regress (just like in AGA).

    So here is where I’m going with this…

    https://en.wikipedia.org/wiki/STAT3

    If you click on the “gene ontology” tab on the right hand side of the page, and then scroll down to “Biological Process” and look at the 7th bullet point down from the top: “Positive regulation of gene silencing by miRNA”….. So once again perhaps STAT3 is a path directly allowing this 50+ keratin specific gene silencing to happen via miRNA22.

    1. Hello Matt,

      Maybe you can tell us what your thoughts are concerning the scalp pain / itch a lot AGA sufferers experience in relation to your findings about STAT3.

      I found this pubmed article:

      http://www.ncbi.nlm.nih.gov/m/pubmed/26193341/

      Again STAT3 suppression / inhibition is is discussed in this article case. Also the spinal cord is involved when it comes to dermatis and itch.

      Although I am not able to dive into the details as deep as you can, I am convinced the JAK inhibitors will be able to solve lots of our issues related to skin and hair.

      There will be a time without scalp pain, psoriasis, dermatitis, vitiligo, AA and AGA. Even hair loss caused by chemo may be solved later as soon as the patients body is normalized and is able to handle the JAK/ immuno suppressants.

      At the same time, when it comes to grey hair and vitiligo, I think they are the discoloration twins, if you know what I mean. If JAK solves Vitiligo, it solves Achromotrichia as well.

        1. hey Netshed I’m sure this will be ill received by many but after using cayenne, garlic, onion, and apple cider vinegar (blended up and topically applied on my head) with occasional once a week tee tree oil at night my scalp itch and pain has been GONE for months….. it’s all pretty damn cheap too. It is ridiculous, I know.. and If i sweat the smell comes out which makes me feel uncomfortable but I’ve had pain and itchiness for like 5 to 10 years so it’s worth it to me my hairs never felt healthier.

          Mat I think there is something to the PH level in the scalp and I hear that apple cider vinegar helps balance that what are your thoughts on acidity and inflammation and demodex/mites etc?

          Cliradex Paul S. guy said it was most likely something like blepharitis or demodex. he said to me on the phone “Does is feel like there is a moist goopy layer of itchy skin than peels off like dandruff even if you shower hundreds of times?” -Yes -“okay yeah then that’s probably dixtophgoporcyionaidlititus (some big word) so after that exchange of dialogue I started experimenting with hippy naturals etc. because the Cliradex foam was taking to long to release to market.

          me and my twin brother both have observed and questioned why our scalp hurts and feel itchy. It’s definitely NOT placebo. Our AGA does something to cause itching and pain. I’ve been doing this for 2 months no hair regrowth obviously some tiny terminalishvellous hairs here and there but nothing worth the trouble … but no pain or itching either -AT ALL. my scalp feels healthier hair is stronger and softer and it’s never been like this my entire adult life and my girlfriend notices it too she said “it feels stronger”.

          I would say the experiment was a total failure so far 60 days in reversing AGA but a total success in stopping whatever the hell the pain and itching problem was.

          1. Hello Egghead,

            I confirm that ACV works when it comes to an itchy scaly scalp and face. People who downplay it, never tried it I suppose.

            What is really weird about the scalp pain is that it occurs in conjunction with hair loss at the crown and not with hair loss at the temples, at least that is my experience.

            This might be in line with what some sufferers report, being that the current (almost useless) treatments have some minor effect in the crown but none in the front zone.

    1. AND ask if these JAK inhibitors are even economically feasible!…like seriously, if it cost as much as a hair transplant, but you have to continually apply it, it is worthless…from what I see, Oral JAK is very expensive.

  3. I don’t think we should underestimate any of the findings Matt’s presenting in these comments. Some of the links he’s making seem unprecedented, and I only wish I had more knowledge to help him out – I’m reading everything I can to try and catch up!

    Interesting line I found on the inflammation angle though:
    “A study shows that benoxaprofen, or other lipoxygenase-inhibiting agents, might be helpful in the treatment of psoriasis because the migration inhibition of the inflammatory cells (leukocytes) into the skin”

    Keep up the amazing work Matt!

    1. Wow…. look at these articles in relation to all previous posts I and others have posted

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653025/

      There is definitely something to this whole miRNA-22 and JAK/STAT pathway thing going on in hair. In this other cancerous t-cell population it looks like like JAK/STAT pathway is actually supressing miRNA-22. Specifically this article mentions JAK3/STAT3/STAT5…. Notice how Walker talked about developing a JAK3 inhibitor as apposed to the others…

      miRNA-22 functions as a “tumor suppressor”. Aka it stunts the growth of cells. The exact thing we are seeing in the actual hair shaft part of the hair follicle in AGA. Difference between AGA and AA? One is an adaptive immune response (AGA) and the other is an innate response (AA). Which explains the different timescales to lose hair, and explains the pattern somewhat. We also know from above posts that STAT3 is a positive regulator of miRNA gene suppression. And it is known that miRNA-22 is androgen induced from previous posts. And you may look this up if you wish, but estrogen/estrogen receptor and androgen/androgen receptor are regulated differently by miRNA-22 in different cancers.

      Based off of in human trials and on mice, we know that lowering/blocking of JAK/STAT signaling allows hair to grow. When it is high, it is a stop signal in the hair follicle. That much is obvious. This not only works in rodents but in humans. We also know that miRNA-22 functions in hair to stop it from growing by suppressing 50+ keratin genes (and probably others)…. see above article for that. Causing the follicle to regress according to above posted article… exactly like the parthenogenesis of AGA. Also the miRNA-22 promoter is located on the same DNA region in mice and in humans per the article I posted above.

      miRNA22 is also implicated in endothelial cell cellular senescence…. We know this is going on in AGA dp cells, perhaps once again through the JAK/STAT pathway? Relieving this reverses senescence. See the below abstract

      http://www.ncbi.nlm.nih.gov/pubmed/25323119

      Also miRNA-22 regulates smooth muscle cell differentiation. Smooth muscle cell is what the erector pili muscle is made of, in which contact is lost in AGA. Could stopping miRNA-22 jak/stat signaling allow the erector pilli muscle to make contact again? See the below abstract.

      http://www.ncbi.nlm.nih.gov/pubmed/25722434

      Here is where this gets interesting to me….

      http://www.genecards.org/cgi-bin/carddisp.pl?gene=MIR22

      The gene coding for miRNA-22 is on chromosome 17. And it appears that the genes coding for stat3, stat5a, and stat5b are ALSO on chromosome 17.

      http://www.genecards.org/cgi-bin/carddisp.pl?gene=STAT3&keywords=stat3

      http://www.genecards.org/cgi-bin/carddisp.pl?gene=STAT5A&keywords=stat5

      http://www.genecards.org/cgi-bin/carddisp.pl?gene=STAT5B&keywords=stat5

      Note that stat1, stat2, stat4, and stat6 are not on the same chromosome…. So perhaps this micro RNA is promoting stat3 and stat5 over-expression in AGA.

      miRNA’s main function is to post transcriptionally regulate gene expression.

      STAT’s stands for “SIGNAL TRANSDUCER ACTIVATOR OF TRANSCRIPTION.” It would only make sense that something like this is the main problem in AGA. It looks super complicated from the outside because so much is going on. But perhaps it is one or two master switches causing the cascade of crap to happen. This is what I believe at least.

      Man, I am more confident then ever that proper JAK/STAT inhibition via a topical is truly it. I could be completely wrong, but it sure looks like jak/stat signaling has a ton to do with all of hair biology (really, all of biology in general) not just AA.

        1. Only if she gives me a batch of potent topical JAK/stat inhibitor right away lol. I have a feeling she already knows. Don’t forget the research you read is usually 2/3 year behind what these scientists are actually doing. I just think there is no way this hasn’t been tried out yet. They don’t want competitors right on their tail. Plus she studies the genetics behind this all, so I really believe she knows by now. Hell, IMO I think when it’s all said and done maybe this will be MORE effective for AGA than AA bc in AA this all happens rapidly, you are dealing with a forceful attack on the follicles, whereas in AGA it is usually a pretty slow process. Either way I’m quite convinced this is going to nail AGA. Everything looks like it fits on paper. Just need to wait 50+ years to get through the FDA 🙂

          1. Forgot to mention above, JAK3 is the commonality to both stat3 and stat5a/b. That is why I think they are going to try and target the JAK3 receptor as apposed to the JAK 1 receptor.

          2. Ha, was making a joke it won’t take 50 years lol. But I think it could take a while. That’s just how it works with FDA trials.

          3. Hehe i know you were joking about 50 but when they have found the right ‘mix’ voor Jak that works. Couldn’t they start mass fabricating it in 2-3 years?

  4. In cots we trust ! He has been working in wound healing since 2005. Infact he established follica after he discovered wounding technique and not established follica to discover the technique. He just knows how to be quite for long time : -)

    1. Have you ever considered doing Astressin-b injections? The trial on mice was done by injections so I’m assuming doing it orally will do nothing.

    2. When I go to the webshop it states Not For Sale, I live in Europe. So I think it’s blocked for this continent as well.

      1. That’s interesting. Why only Mexico? I truely believe emotional stress plays a role in hair loss, and the corticotropin releasing hormone cascade augments many different physiological systems in our bodies.

        I actually trust in DS labs. They make a topical DNC-f7 (topical astressin-b) but I want the PO (Oral) dosage form. My neighbor is a retired dermatologist (went to allopathic US school), and I’ve talked to him about hair loss before. I wonder if he can pull some strings and get me this integra

        1. You could be right. My hair loss started after suffering a significant injury playing baseball. Never had one before and was devastated recovering from it 🙁

  5. Nasa rs or admin, please answer. Can either of you please tell me if NASA RS is in some way affiliated with the research going into this or is he just a regular guy that’s doing a lot of research?
    The timing of the announcement and when he wanted to release his information was uncanny. It makes me think he has inside info

  6. Regarding river town therapeutics, how come they are in phase 2 for AGA product and no one has heard of them? They are claiming regrowth in bald areas…Anyone knows smth?

  7. Riverine is in phase two yet no pics. If I had a money maker your damn well im gonna post pics and watch my stock go up up and away!

  8. How can I get a prescription for JAK? Does anybody know of any websites or doctors that give out prescriptions easily?

  9. Cant do fin. Cant do minox. Cant do nizoral. Anyone have any suggestions until a new treatment arrives? Fyi im scheduled for prp in a month or so . This blows

  10. Man we need a new treatment asap! This is just getting completely ridiculous and unfair. Don’t these companies have any compassion for our suffering

    1. @mjones … dude if you read my comment properly I was telling people who are in false hopes, that there is nothing that is coming out too soon, I was saying that if something comes out it will be on the news and why some of you think I wanna trash any company..I would be the happiest person if a cure comes out…I am just being practical here…not cursing the companies like you do…so read properly before comment

  11. Admin wanted to post a new article about jak but I think no need for that. Maybe a brief item for june is better ?

    1. If it says 8 to 15 years away I would just completely write it off. Lauster has been in the game since 2001. If he needs another 8 to 15 years then he has jack sht! We shouldn’t even talk about him anymore.

      @farhan. I wasn’t responding back to your post. I was just in general complaining how it’s taking forever for a new treatment to come out. I’m losing my patience and hope for these companies.. I have been considering an FUE for my front right half of my hairline where it’s complete diffuse. I have the ugliest pattern loss:(

      1. Dude get a fue… Stop wasting your time.. I doubt even if a cure comes it will be strong enough to grow in the temples.. Only do it from a really good surgeon… I did it and for three years I didn’t even think about hair loss for a day

        1. Stop advocating for HT, Farhan. You will regret your decision in 15 years. I have met HT recipients, and have read many posts online. I have not seen one recipient who did not regret it 15-20 years later. It starts off fine, if you are lucky, but it does not end well. You still are losing your hair.. and it will continue…

      2. If you have a big a with zero effect from AGA in you donor área FUE is Good alternative. If not you will regret it.

        Best solution is shave it and get a Good sun in the head XD nobody will Know you are bald.

  12. Hi Matt , help me please . You seem very knowledgeable. According to your own knowledge, what is the best dosage and the right ingredients to make a cream with tofacitinib . Can you do me a detailed list please . I order the Tofa and ingredients shortly. Thank you. William

  13. Hey guys,

    Long time lurker, not much of a poster!

    For any of you scientists out there (real, armchair or otherwise), do you think there will be an contraindications for JAK treatment for those of us that have been diagnosed with melanoma previously?

    I hope this q doesn’t get lost in the replies! This thread is crazy.

    1. Post your question again in the newest thread the admin posted. I just got off work and we’ll try to answer later in the week. Here are my credentials: I have a BS in Biology, minor in chemistry, am in my 3rd year of pharmacy school, and I work at an internationally known academic medical center.

  14. @Susana
    Seems that they have evidence that it works for people with MPB. Watch/Listen the presentation again please.
    Daniel G
    JUNE 8, 2016 AT 2:14 PM
    They said in the presentation that topical JAK inhibitors work for AGA.

  15. Neal Walker needs to provide us with before after pics of jak on mpb! We deserve at least some evidence that it works great. That will boost mine and many other people’s confidence knowing that a great mpb treatment is on its way. Sitting here hearing the same old song and dance with no real picture evidence is brutal waiting and waiting

    1. They dont even have jaks for mpb on their website of drugs in the pipeline, not even the very first step! The people thinking (if it even works or is financially feasible) it will be out any time soon are crazy! This was mentioned where at an investor conference, hoping to get investors and stock upgrades and recomendations from analysts which then cause their stock to appreciate. They can then issue more shares and essentially use their stock as a currency to grow and make aqcuistions and raise capital…the hype over nothing is crazy. hopefully it works and regrows hair, “matt” makes some solid arguements connecting the dots of why it should.

        1. Something that scientific research companies and very bad at is website management, because they work on funding and don’t waste money on IT people. We know that JAK for AGA is in early stages still, so it’s not surprising to see a lack of info on their website. Look how rarely histogen update theirs for example.

  16. So now this thread ends like every other = it wont see release for the next 10 years. Releax people give them a chance to get everything in order. We just got the next a few days ago. Hopefully we’ll hear more very soon:-)
    @matt, Thank you for all the technical insight, its amazing!!

  17. Admin when can we expect some new news related because now this thread has gone in another phase.

    Actually in your earlier comments you seem to preparing for some another interesting post and now i am only curious for that. Please release that.

    1. Below is how Dr Christiano describes making the cream in her study.

      “Ruxolitinib was purchased from ChemieTek (catalog no. CT-INCB). Tofacitinib was purchased from AbMole BioScience (catalog no. 477600-75-2). Hedgehog agonist (SAG) was purchased from EMD Millipore (catalog no. 566660). JAK-STAT inhibitors were dissolved in DMSO and used at 2 to 3% for in vivo experiments, as indicated, and 400 nM for in vitro experiments. SAG was used at 120 μM, as described by Paladini et al. (2).”

      http://advances.sciencemag.org/content/1/9/e1500973.full

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