Krox20 and Dr. Lu Le

Krox20 and Hair Growth

By far the biggest news this month was the story that scientists at UT Southwestern Medical Center in the US found that a specific protein in skin cells called Krox20 (also known as EGR2) turns on hair shaft progenitor cells and is therefore responsible for the initiation of hair growth on the scalp. Moreover, these same progenitors also produce a protein called stem cell factor (SCF), which the researchers showed is essential for giving hair its pigmentation. Full study here. The research team was led by Dr. Lu Le.

There were 100 plus headline stories about this in the global media, and at least 10 people posted links about this story in two blog posts from earlier this month or emailed me in person. I always appreciate hearing about groundbreaking new information, but I wish people would at least skim through the comments for links and make sure the story is not so obvious and widely covered!

Many of the newspaper headlines about this discovery screamed that the cure for grey hair reversal is near (note that this is yet one new approach among many that are being considered to reverse grey hair) and I have covered some of the main discoveries related to both grey hair and the link between skin cells and hair growth on this blog many times in the past.

The main researcher involved in this work (Dr. Lu Le) was actually researching a very specific type of nerve related cancer before stumbling on these interesting findings. At the moment, Dr. Le’s bio page does not even list hair loss as an area of clinical interest for him! However, for those who were paying attention, Dr. Le made one of the main presentations at the recent SID annual conference. His “state-of-the art plenary lecture” was titled:

“Progenitors that Create a Niche for Hair Pigmentation and Graying”.

These findings have yet to even be utilized in any kind of pre-clinical trials, so I was not too excited about this news story and did not write a separate post on it. However, it should be noted that Dr. Le has said the following (and will therefore likely add hair loss to his areas of interest soon):

With this knowledge, we hope in the future to create a topical compound or to safely deliver the necessary gene to hair follicles to correct these cosmetic problems.

Intravenous Immunoglobulin (IVIG) Therapy for Hair Growth

I got far more excited about a new study that came out a few weeks ago titled “The effects of hair regrowth with intravenous immunoglobulin (IVIG) therapy. Two case reports“. Several before and after photos in there that show moderate hair regrowth. The key quote that struck me was:

“A literature review did show two cases where treatment with IVIG led to hair regrowth in alopecia universalis. But there have been no case reports of patients with AGA having substantial hair regrowth with IVIG or other immune modulating or anti-inflammatory drugs. Until now.”

Of course the first thing that came to my mind was JAK inhibitors, since those have worked superbly on patients with alopecia areata (AA), an autoimmune disorder. Aclaris Therapeutics (US) plans to test topical JAK inhibitors on patients with androgenetic alopecia (no autoimmune component) in the future as long time readers of this blog know. Fingers still crossed on that one and hoping for the best, although I am disappointed that we have to rely on just one company (due to Angela Christiano/Columbia University’s sale of the key patents to Aclaris).

— Interesting new paper from Russia titled “Hair Follicle Reconstruction and Stem Cells“. Note that one of the authors is a Dr. Vasily Terskikh, who is not the same (as I originally mistook) as the far more famous hair loss researcher Dr. Alexey Terskikh. Most likely they are related since the latter is also from Russia and involved in hair research.

New paper from Dr. Claire Higgins and team titled “Methods for the isolation and 3D culture of dermal papilla cells from human hair follicles”.

— New study suggests benefits of low level laser therapy (LLLT) on scalp hair growth might have a scientific basis. They found that a 3.2 J/cm2 of 453 nm blue light exerts a positive effect on hair growth ex vivo. In contrast, hair follicle treatment with 3.2 J/cm2 of 689 nm light (red light) did not significantly affect hair growth ex vivo. Make sure to read my post on laser wavelength and hair growth.

And now on to medical items of interest:

An artificial womb successfully grew baby sheep. Humans would be next according to some. This surreal idea was also discussed in this video from last year.

The much anticipated skin gun is back in the news. Apparently, “RenovaCare is applying to the US FDA for permission to use it in routine clinical practice. It will then look to obtain a similar licence in Europe”.

Getting close to mass production of bones, organs and implants.

Type 1 diabetes cured in mice.

HIV eliminated in mice using CRISPR.

I am getting a feeling that everything seems to work in mice, including GW1516.

The most promising way to mental superpowers.

86 thoughts on “Krox20 and Dr. Lu Le”

    1. Definite regrowth in first pic. Second one also has regrowth in front left side balding region. For 1 month I would say good results.

    2. I think the hair growth in the first subject is too much to chalk up to lighting differences, and only at one month after treatment.

      It seems odd that he would get that regrowth from what sounds like, essentially, a blood transfusion. You wouldn’t think something “determined by genetics” could be solved by an immune therapy.

    3. Also this isn’t like histogen or some HT doctor trying to sell PRP. These doctors have no interest in marketing this and they have no skin in the hairloss game. It seems they’re immune specialists who noticed a weird phenomena and decided to write up a quick paper to publish.

      I doubt they would go out of their way to do this if they weren’t legitimately surprised at the hair growth they saw. Otherwise they’d have spent their time making $700/hr in doing their normal day-to-day work.

      1. Great points. Part of the reason I posted about this is because I did not find any reasons to suspect the doctors of anything. The article also seems pretty well written. e.g., sentences such as this:

        “Treatments for AGA so far have focused on reducing free or unbound testosterone, reducing total DHT levels via different mechanisms or by stimulation of hair growth secondary to increase vasodilation and increased cutaneous blood flow via activation of ATP-sensitive potassium channels within the hair follicle.”

    4. @L

      Completely agree. It’s sad that we always have to come back to these basic arguments, but it’s simple: if the lighting and hair length/styling aren’t exactly the same in each picture, it can safely be ignored 100% of the time. In this case, they’re extremely different. Not worth even a second of thought.

      Researchers should know better, especially in this case, where their evidence consists of the pictures themselves rather than any quantifiable data. Are we really going to fall for this time and time again?

      1. Thanks ADMIN. I should have known that your strong due diligence would have found the article. However, it actually offered a potential treatment, that they were testing on rats first, thus I thought it offered hope to us humans too and that’s why I took the chance to post it.

        Nice to actually hear that they are working on a cure and not always just finding out why we lose hair or go grey but an actual treatment.

  1. For the Bloomberg article about mass producing organs, I think this line is interesting – maybe it belongs in the hair loss section:

    “It’s also developing printable bone tissue for skeletal disease research and co-developing 3D-printed skin with L’Oréal SA.”

    And isn’t L’Oreal now a player in the hair loss game? I wonder if Organovo is involved somehow in that venture.

  2. Sadly I have to agree with @L, those pics is as bad and manipulated as Histrogens famous combover pics, No change in the after pics, only different light and angels. Speaking bout Histrogen; I just read on HLT forums that Histrogen wont be out in Mexico before 2020.

  3. Histogen is done. I mean 7 years in delays. That’s a bit excessive. You can’t keep postponing a treatment like that. They don’t have a working treatment plain and simple. If they did it would have been out in 2014 15. She is just pushing for funds to keep her business alive. Sometimes it’s better for a company to be silent like follica so we don’t get disappointed by false claiming release dates.

    1. Histogen was never as hopeful as Replicell anyway, since they only use growth factors and dont introduce new stem cells…

  4. @mjones do you really think histogen is history? But why? Just look the pictures! Is splending ….

  5. I’m actually angry at histogen. They got our hopes up and changed people’s plans inappropriately. I’m sure several delayed transplants or other treatments because they BELIEVED gail. It’s bs. She shouldn’t do that. I know I’m dusgusted.

  6. So now we are without another treatment for at least another 3 years. That’s great!!! Unbelievable!! And the immunoglobulin therapy looks at least somewhat effective however will that ever come out??!! Doubt it!

  7. Why is everyone surprised.? I’m not. This is the name of the game in hair loss research. It’s all bs. They don’t have anything plain and simple. For all we know that picture was photoshopped. If that was really the results Histogen would have been in the market by now. Investors from all over the place would fund it to hit market back in 2015. I’m forgetting about histocrap. Personally I wouldn’t go to Mexico to get anything injected into my scalp. Not a racial thing but more of a safety law regulation thing.

    1. You are 100% right mjones. Money would be pouring in left and right if they actually had anything.

      1. Share your frustration, but instead of just complaining contribute to the research by donating. I participated Replicel’s newest round (mostly because of their tendon/skin treatments). This attitude is partly responsible for there not being new treatments sooner. If you dont like the present contribute to changing it instead of not doing anything. If Histogen had the money the product would be in phase 3 already. The proyections in general have always been made assuming funding rounds are complete. They obviously cannot release without studies and approval!

  8. If anyone is interested the poster on HLT uploaded histogens investor doc (link below) which points to a likely Q4 2019 release mentioned above. Personally I’m still happy with the possibility. I’m overall still excited that there are so many potential treatments/solutions on the horizon.

    They say ‘When it rains, it pours’ and we may have a monsoon in the run up to 2020 after a long drought!

    Never lose hope.

  9. Maybe you are right Hairplz. I should donate all my money to a company that already got millions from China to pursue the trials. Instead they are pocketing it and putting towards their other treatments that probably actually work. I’ll tell you one thing, I would donate money to their photographer at the trials. I would hire a photographer other than dr. Ziering. An honest photographer who would take real untouched photos. I’m not trashing all hair loss companies, just the shady ones. I’m a big fan of follica, sisheido, SM, my favorite is Merk. Propecia was the only hair loss drug that worked for me.

  10. You guys you guys don’t worry Brotzu’s got a lotion you gotta check out forget Histogen right Brotzu!?….. Brotzu?

  11. Brotzu is the next kelopesia. I don’t think anybody knows what Brotzu is except for people in hair loss forums. I wouldn’t hold much promise on that treatment lol. At least histogen showed a picture in color and not black and white from some publication lol

    1. I agree with you on sm and follica but have to say I think you may be off on Brotzu, lots are saying the science behind it is legit.

      1. Don’t listen to these guys most of them are crazy. A pharmaceutical company purchased his patent and are doing trials with the lotion already so I believe it exists but if it works as good as what they say we will see soon

    2. you are a broken record…Brotzu is legit and has actual potential. He has been more productive in life than your idol Cots, that’s for sure.

  12. People forgot that Histogen got sued a little while and it took some time for them to win which of course delayed their process. The 2018-2019 date was for Mexico because other countries’ version of the FDA aren’t as strict as in the US.

    Why did people forget that? It’s so much easier to complain, it doesn’t make the treatment come quicker.

  13. Was Wasabi applied topically ?in the study it doesn’t really specify.. It seems it was in vitro..

  14. Unfortunately, its very common that directly and indirectly government-funded research projects are prolonged and drug releases are postponed. On average it takes 10 to 15 years from discovery to release. Such a release most of the time only serves a small niche in the entire healthcare spectrum, meaning that only a small portion of patients will benefit from it. And well, as AGA research is not funded by any governmental body (well okay, the Japanese seem very interested in regenerative medicine), it probably takes longer than 10/15 years.

    Even if they simultaneously can generate a lot of cash with for instance KROX20 or FOXO4-DRI against AGA, and consequently obtain even more money to support their more significant research, the first 15 years they still will choose for the research that gives them the highest scientific reputation, and you all know what that means for us.

  15. Well said Netshed!

    @Guest. Cots is a well known hair loss researcher that has been focused soley on hair loss. Brotzu just popped out of nowhere with a topical that is aimed and trialed for AA that came from a fluke heart drug or whatever it was. Cots has been on many large news channels and large dermatological conferences. Brotzu is still unknown by people outside of HLT and this website. You can put all your hope in brotzu that is your choice and I don’t knock you for it because hope is all we really have in this hair loss game but don’t go trash a worldwide known top hair loss researcher funded by millions and starting pivotal and phase 3 trials this fall because you feel he isn’t good. Per netshed comment hair loss treatments take longer to hit market and follica is right schedule with the 10 to 15 year time line.

    1. @mjones, you should read up properly on Brotzu. Im not saying that the lotion will turn out to be a cure, but it really could be something that can atleast halt hair loss and give procepia-like results. Do yourself a favour and do a little reading on the topic, I think you’ll be pleasantly surprised;-)

  16. Here is what I am thinking on Isosaponarin. It increases type 1 collagen synthesis like replicels cells do, but also like Biosil. Biosil is clinically proven to help hair diameter (increases hair thinkness). The going hypothesis I believe is that blood vessels with more collagen are more flexible/useful and feed the dermal papilla cells much better.

  17. Theoretically AGA is just an old mans disease. Disappointingly, in practice it’s about a lot of (very) young people getting an old mans disease. One year ago this guy one Quora gave a great summary on what is going on:

    Step 1: DHT promotes hair growth
    Step 2: For those who are destined to have AGA: The cells of the dermal papilla (on top of the head) act differently / are more likely to be senescent, which means that the cells just age too fast. Eventually you are ‘running out of stock’, you are running out of ‘hair producing cells’ early in life
    Step 3: Senescent cells are a way of the body to hedge against cancer. The body seems to prefer and maintain this kind of status quo against cancer
    Step 4: Accordingly, your immune system might attack the senescent cells. Probably leading to inflammation, which some of us perceive as a painful/ bruised / itching / burning scalp

    Step 1: Diminishing DHT might help
    Step 2: Replenishing ‘hair producing cells’ might help
    Step 3: Destroying senescent cells might help
    Step 4: Immunosuppressants / inhibitors might help
    Step 0: Cloning might solve all / CRISPR might prevent all

    From my personal experience:
    My hair on the crown always was the thickest part, it grew faster than the rest. Hairdressers had a problem with the scissors to cut it because of the fullness in that area. Afterwards it looks like DHT overpromoted hair growth there (some trichologists call that Hypergrowth) . While I thought everything was going great, I already was running out of stock of hair producing cells a few years later. Now that the bald spot on my crown is growing and growing, and doesn’t respond to any treatment, it looks like my body likes the so called status quo, so keeping the cells quiet (as the guy on Quora said : “hedge against cancer”). Once in a while it looks like my immune system awakens and starts attacking some of those senescent cells, which leads to the painful scalp. It all fits in the Quora story.

    Congratulations, you all have an old (wo)mans scalp!
    It looks old, and it actually is old. What you see, is what you have.
    Cheers :)

    1. What your suggesting is that our scalp is experiencing a centralized form of Progeria? There should be a very good correlation between mpb and tumors of the scalp.

  18. I have a question. Do those of you who have AGA also have other skin conditions? Hiw many people who are balding or thining also have adult acne? How many of you sweat either prematurely or excessively? I’m curious if these are related?

    1. It is pointless to ask for such anecdotal evidence, it would only be significant if you tested a large sample of the population. MPB is so rampant you could make any correlation you like, such as ‘is having a penis associated with MPB?’.
      Of course its correlated, but that doesn’t mean chopping your knob off is going to grow your hair back.

  19. The hairloss stuff is always disappointing. But the medical advances elsewhere are very exciting. We are living in a new era of precision gene editing and machine learning that should hopefully be fruitful within our lifetime. I see no reason why hairloss will also not benefit even if it is not the major point of focus right now

  20. Enhancing hair growth in male androgenetic alopecia by a combination of fractional CO2 laser therapy and hair growth factors.

    Global photographs showed improvement in 93% (25/27) patients in the combined group and 67% (18/27) patients in the growth factor group. Under scanning electron microscopy, hair follicles appeared to transition from telogen to anagen, and hair-shaft diameter increased in five randomly selected patients. Ablative fractional CO2 laser combined with hair growth factors may serve as an alternative treatment for MAA in individuals unwilling/unable to undergo medical or surgical treatment.

  21. @omg good find..I would to know what these growth factors are and who was responsible for this study. Ten bucks it just gets patented and no one buys it!

    1. Unfortunately that’s probably what will happen. I bet it’s this simple to restore a ton of hair and it will just get shelved. This method of laser and growth factors sounds much better than fue

  22. There is a picture of some dude who applied a remake of brontzu lotion over at HLT. Growth looks decent for a couple months use and doesn’t seem photoshopped.

  23. Looks like Brotzu works to some degree. The most recent Italian group buy participants (not the fake minoxidil scam GB) got the lotion made by a professional lab who strictly followed Brotzu’s patent. Multiple GB participants are reporting significant results (vellus regrowth on both vertex and temples, along with a complete stoppage of shedding and sebum) after only a few months of use.

    IESON thread:

    And yes Mjones, there are colored pictures of the group buy results on both the HLT forum thread, as well as many more on the Italian Hair loss forum. The results look good imo.

    Keep in mind the group buy lotion pales in comparison to Fidia’s actual lotion, since the Fidia lotion will have superior dosage and will make use of Liposomal delivery, which Dr. Brotzu has been on record stating is a key mechanism for the lotions effectiveness.

    If the much inferior group buy lotion is yielding results already, I am excited to see what the official lotion is capable of.

  24. Mjones do u know where they are doing the clinical trials for the co2 laser and growth compounds? Maybe one of us can enroll?

    Aaaaaaand the brotzu train is gathering momentum once again.

    Anyone on here participating in the Setipiprant trial? There was a guy on here a while back that told me that he was going to enroll however I forget his name ahhh.

  25. @newerah, noone knows the answer to this but Fidia.
    The GB lotion pics on HLT looks really promising. Lets hope its legit:-0 Seems like it is…

  26. @ Netshed Senolytics I know of:
    (From Wikipedia:)
    At some point I will pop these and see my damn human body either live eternal or die young, where’s the difference anyway.

    @ Red Thanks, I usually don’t follow the forums, but Brotzu looks promising.

    @ tom They use laser irradiation plus human hair growth factors, FGF-2, IL-3, IL-6, IL-7, IL-8, TGF-β1, TGF-β2 and TGF-β3 from foreskin. 2 ml on the scalp once every other day. They show photos but tbh, I see no major improvement at the 4 month mark.

    You can use to access these papers.

    1. Even if one could live eternal remember that same shit human society, murderers, rapists, pedophiles and racists will live on aswell. But I know, we’re talking about our damn scalps killing off some senescent cells.

  27. Italian photos seems b (again).
    Differents lights and angles (…)
    For the temples, look the first and makes the comparison with the second: same hair wich have grown

  28. The problem with these senescent cells seems to be that, over time, they lose their tumor suppressing power. So in the first place they take over your scalp to early in life leading to AGA.

    And in the second place, later in life when they probably are actually needed for tumor suppression (the older we are, the higher the risk of wrong cell mutations) they are useless or less powerful than they should be.

    Those cells act like your old colleague, who is always too early at the office in the morning, who is bored because nothing has to be done yet at that time, and who starts destroying your state-of-the-art Excel files.

    By the time, the end of the work shift emerges, and the deadlines are still flooding your Outlook, your colleague could be a great assistent to answer the requests, however he is already out of energy or has left the office 2 hours ago for his Origami class.

  29. can any get into this?

    Hair Regeneration Therapy Using Proteins Secreted by Adipose-Derived Stem Cells

    Adipose-derived stem cells secrete various cytokines that promote hair growth. We have used adipose-derived stem cell-conditioned medium to treat alopecia and reported good results. In this article, we describe our experience of the hair regeneration therapy including characteristics of the commercialized conditioned medium, treatment methods, and future directions. Treatment using adipose-derived stem cell-conditioned medium is highly effective and may represent a new therapy for alopecia.

  30. OK. Lets talk the true about the photos from the home made Brotzu lotion.

    You really see more hair right? OK
    1 question for you all!
    Hair grow 1 cm for each month . You can watch new hair with 1 cm?
    All hair there have 5cm or more.
    You still believe in new hair there?

  31. I’m with you ana. The hair was clearly trimmed. Notice the thickness of the supposed new hairs! When ever new hair grows in it cycles in and gets thicker, not start off that thick. I want to believe but I don’t want to kid myself.

  32. And no wonder allergen is having a difficult time getting people to sign up for the setipiprant trial. If you go to their site it doesn’t have an option to sign up like all the other trials they are doing. I don’t even think they know that their trial isn’t listed.

  33. we need data for hair regrowth to confirm if bortzu sam others are effective treatments. we can not rely on pictures.

  34. J Nat Med. 2010 Jul;64(3):305-12. doi: 10.1007/s11418-010-0412-y. Epub 2010 Mar 27.
    The effect of isosaponarin isolated from wasabi leaf on collagen synthesis in human fibroblasts and its underlying mechanism.
    Nagai M1, Akita K, Yamada K, Okunishi I.
    Author information

    Wasabi has been used as an important spice in Japanese foods. The wasabi leaves were used as a cosmetic material, but its biological activities have not yet been examined. We investigated the effect of isosaponarin derived from wasabi leaf on collagen synthesis in human fibroblasts. The production of type I collagen in human fibroblasts was increased with treatment of wasabi leaf extract. Isosaponarin isolated from wasabi leaves belonged to the group of flavone glycoside, and was the key compound in collagen synthesis from the wasabi leaf ingredients. Isosaponarin increased the type I collagen production at the mRNA gene level. The treatment of isosaponarin did not influence the production of transforming growth factor-beta (TGF-beta) protein, but increased the production of TGF-beta type II receptor (TbetaR-II) protein and TbetaR-II mRNA. Prolyl 4-hydroxylase (P4H) protein and P4H mRNA were increased by treatment with isosaponarin. Heat shock protein 47 (HSP47) was not increased by treatment with isosaponarin. These results suggested that isosaponarin increased collagen synthesis in human fibroblasts, caused by up-regulated TbetaR-II and P4H production.

  35. Why is everything in the hair loss industry so disappointing….ugggggh. It’s scam pictures, to postponed released dates, to wasabi and other natural that prob don’t work to conspiracy theories to hyped up treatments that ghost on us. Is this some giant corporate kick in the balls to us suffering individuals? I really don’t get it. I don’t expect a cure but sht, a new advanced treatment with legit data and pictures that shows someone actually growing thick normal hair strands thar densely covers someone’s crown or frontal areas. 3 nwds improve. Let it be something we need to take for life I don’t care as long as it works really well…I’m willing to pay haha never seen an industry so much in failure in my life. We can skin, vaginas, cells, organs but a follicle is just out of this world. Wtf. Sorry for the rant guys. I just really don’t want to get an ht and holding on as long as I can. Never thought back in 2001 when I started Propecia that I wouldn’t have a better treatment to use by 2017, I was certain cloning was coming by 2010. Still in the same freaking boat.

  36. Admin, if you wouldn’t mind, I think it’s about time to get feedback on the prp giveaway experience with rapaport. What’s the word?

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