The Sonic Hedgehog Pathway — An Unrealized Dream

Perhaps the most important area of hair loss research that I have not yet covered on this blog relates to the Sonic Hedgehog (SHH) protein and signaling pathway. While the sonic hedgehog protein has numerous critical effects on a developing human embryo (brain, craniofacial, lungs, teeth and more), it also continues to be important in adulthood when it controls certain stem cell division activities. Getting into too much detail about this would go beyond the scope of this blog. SHH was named after SEGA’s famous video game character, Sonic the Hedgehog.

Sato, Leopold and Crystal (1999)

In the initial decade after the first identification of the hedgehog gene around 1980, there was almost no research devoted to the impact of  SHH upon human hair. However, this started to change in the mid-1990s (e.g., this from 1998) and culminated in the seminal work on this subject that was published in the US in 1999: “Induction of the hair growth phase in postnatal mice by localized transient expression of Sonic hedgehog“.

Dr. Ronald Crystal: Sonic Hedgehog

Of the three authors of the above study, the most cited was Cornell based Dr. Ronald Crystal who remains in practice even today.

What these authors discovered was that after injecting balding mice hair cells with the sonic hedgehog gene using an adenovirus, resting hair follicles in the mice started growing robust hair of the mouse’s native hair color (they dyed all the fur blonde so as to differentiate the newly growing hair). Moreover, upon final analysis, the team found that the SHH gene was active in the injected areas of the skin, but not elsewhere. A very humorous and at the same time highly informative article on this subject from 1999 can be read here.

Curis-Procter & Gamble RIP (2005-2007)

After the groundbreaking 1999 study on mice, some researchers were mildly optimistic that SHH activation could also have positive implications on human hair growth in balding men and women. A new company that was formed in 2000 called Curis partnered with Procter & Gamble in 2005 to try and develop a topical Hedgehog agonist product for scalp hair growth. However, this partnership was ended in 2007 due to potential safety issues since SHH can potentially also cause basal cell carcinoma cancer. P&G was not willing to continue with the drug development work, since even a very minimal risk of developing cancer is not worth it for treating a cosmetic problem such as hair loss (at least in the eyes of government). Interesting comment from the at-the-time CEO of Curis:

We are obviously disappointed that the collaboration with Procter & Gamble will come to an end. We believe that our topically administered Hedgehog agonists have demonstrated encouraging efficacy in preclinical hair growth models and we were hopeful that one of our Hedgehog agonist drug candidates under the program would have progressed.

Current Status

While the initial excitement of a SHH based cure for hair loss has long ended, sporadic research activity in this area continues (e.g, this in 2016). Moreover, in 2013, scientists even found that SHH signaling regenerates ear hair cells.

On a related note, also make sure to read my post from earlier this year regarding ear hair regeneration and possible links with scalp hair regeneration (some controversy in that analogy if you read the comments to that post).

56 thoughts on “The Sonic Hedgehog Pathway — An Unrealized Dream”

  1. @admin

    I think it’s time for you to enroll in some biology classes and start your medical career.

    Or become an author of “history of hairloss”.
    A book about history of cancer titled “emperor of all maladies” won the Pulitzer.

    Or may be start an ice bucket challenge to collect funding for hair loss research. We should actually have bald dudes breaking various things on their head to show how frustrated they are. The bigger the object, the bigger the donation. We can start with an egg.

    -:)

  2. Ha..ha..ha…
    Frustated, but cmnt like this makes me laugh and frustration goes away…

    Thanks a lot Admin for this blog.

  3. Hi Admin, just wanna to say that very impressed with your finding & research on hairloss history and information. Kudos to you and keep up the good job. wish one day you will announce you closing the site down because no longer needed anymore to keep us posted about hairloss because the cure/treatment is out there for us.

  4. Admin, your dedication to this research and keeping everything grouped together and updated is truly invaluable. Thank you. I really do believe medicine is on the cusp of some amazing new treatments for everything and that we’ll see something big (crispr, hair regeneration, cancer cure) within the next decade which will unleash the floodgates to enormous possibilities.

  5. http://www.folliclethought.com/asia-hair-growth-rd/
    New article in FollicleThought…Not bad…
    Does anyone else think we will not have a cure or a new treatment in 10,000 years? Mother of God … you have to be naive…It seems embarrassing to me that there is no advance in decades in the hair loss industry … it’s incredible …
    Soon we will have more good news. About… ****** 🙂

    GREAT BLOG ADMIN AS ALWAYS.

      1. Ya they are all in preclinical or phase 1 anyway a decade away from the states but congrats to Folliclethought not peddling affiliate links like a petty salesman I guess

        No one is news unless they are pre 2021

    1. @PaulPheonix there is no evidence that a truly effective cure or treatment is forthcoming. These incidental news items – while interesting – are proof of nothing. All the news just repeats itself. Sad but true.

  6. @hanginginthewire don’t forget Tsuji, man. The cure is in sight. Maintenance in the forms of follica, possibly polichem are even closer. Brotzu is anybody’s guess at this moment I suppose, but there are certainly new treatments coming.

    1. Agreed. I think Tsuji’s work is the greatest case for optimism but still needs to be proven further it can work on mass scale.

  7. as someone from pharma company, safety is the first and foremost topic on our agenda. no one in pharma wants to be associated with products causing cancer and such. So I cna obviously understand why P&G withdrawn.

    My opinion, SHH is indeed the cure for hairloss. I dont think any other treatments can even come close. Same logic, you can also try developing spidey skills by getting biten by an irradiated spider. Most probably you will be dead within next few hours.
    this is very much same logic otherwise P&G would have stayed and continued working on it. Because hairloss is a chicken laying golden eggs… no one denies it

    1. @Paulpheonix I admire your optimism but I don’t share it. Yes hair loss is going to be cured. No it’s not gonna be anytime soon, or soon enough to benefit us.

      1. I find it hard to believe that DHT has so many critical benefits in adults. That source Netshed posted sells DHT and other blood tests FYI and I would not count it as unbiased.

        Women live longer than men and have drastically less DHT and testosterone (and much more estrogen).

        To really believe all that stuff, you would need to find a few reputable studies for each item they list there —

        e.g., studies that show low DHT levels lead to higher stroke rates. Similar one for heart disease. Similar one for diabetes. Similar one for depression etc…really doubt any of those are true (except of course things such as less sex drive, gyno etc…) that have been noted many times in an assortment of reputable studies.

    1. Admin is right, they are selling stuff. hmm
      Either way, there are ‘indications’ that they might be right about:

      Male Development
      Libido
      Prostate Health
      Cognitive Function
      Depression
      Because we all know what studies there are about a certain hair loss drug. But let’s not get into a discussion again about that Merck thing. Some hate it, some love it 🙂

  8. IMHO hair is a very important condition…It’s beoming more relevant in this society. We will have a new treatment soon. The big 3 will be the past…Is strange all people with MPB thinks 2018 is the year!!!!

  9. Any cure for baldness will provide a great boost to the world economy. Older men have more money and if their confidence and optimism rises so will their spending on entertainment, clothes, holidays etc.

  10. Oxidative stress management in the hair follicle: Could targeting NRF2 counter age-related hair disorders and beyond?

    Small molecule activators of NRF2 may therefore be useful in the management of HF pathologies associated with redox imbalance, ranging from HF greying and HF ageing via androgenetic alopecia and alopecia areata to chemotherapy-induced hair loss

    https://www.ncbi.nlm.nih.gov/pubmed/28685843

  11. Generation of Human Hair Cells In Vitro: Is It
    All about How the Wnt Blows?

    In humans, and all other mammals, hearing
    and balance are dependent on a
    shockingly small number of mechanosensory
    hair cells. At birth, each of our ears
    contains approximately 75,000 of these
    magnificently sensitive mechanosensors:
    15,000 in the cochlea and 60,000 in the
    vestibular system. However, with age,
    and in response to various environmental
    insults, these cells are gradually lost,
    potentially leading to an isolating hearing
    impairment or debilitating vertigo. While
    recent results suggest that some vestibular
    hair cells may spontaneously regenerate,
    the numbers seem to be too
    small to be clinically relevant

    https://sci-hub.io/10.1016/j.stem.2017.06.007

  12. This comment is completely unrelated to this thread but I think it’s worth sharing as I’m sure there are a lot of readers in the same boat as I was.

    So, this weekend I shaved my head. Well, my barber did. We’ve always had an agreement that he will tell me when it’s time to bite the bullet and buzz it down. Every time I would go in expecting him to tell me that today is the day. But for the last year or so I’ve been walking out with hair. Well, some hair. But today I walked in there knowing that it was time. I sat down, pulled off my cap, and said, “today is the day. Let’s do it.” He ran his fingers through what was left and asked if I was sure. I nodded my head, closed my eyes, and the clippers did their thing.

    Now, I’m not going to pretend it wasn’t traumatic. I’m not going to pretend I haven’t caught my reflection in storefronts and car windows over the last couple of days and been a little shocked at what was staring back at me. But the relief I now feel – the weight that has been lifted off my shoulders – is palpable.

    No more wearing a cap every single day.
    No more around in the mirror, fashioning interesting shapes and comb-overs to make some sort of style work with what was left.
    No more Toppik.
    No more fearing downlights.
    No more fearing the slightest breeze.
    No more asking the Uber driver to put up the car window.
    No more avoiding swimming, even when it’s hot as balls.
    No more checking this blog twice a day (I’ll still probably check in weekly 😉

    For anyone else out there thinking of shaving their head, maybe this post will help you take the plunge.

    Just do it and own it.
    I wish I did it sooner.

  13. Charablaze, hanginginthewire, pimmler….do not feed the troll. They know we will have new alternatives and more treatments for mpb the next year…that’s life…

    1. @newerah, I am no troll. My depression over hair loss is unspeakable. I hope and pray that there is a new (effective) treatment or cure soon. My future looks mighty bleak without one. This will be my last post repeating it cause I don’t want o spam the thread, but I know what false hope looks like, hope born out of wishful thinking and desperation. There’s no evidence that 2018 is gonna be some kind of gamechanger. And when 2018 comes and goes and we are still suffering, the positivity brigade will move the goalposts and start amping everyone up for 2019…2020…no 2021. On and on it goes. Some of us are not mentally equipped to deal with the inevitable disappointment.

  14. http://www.express.co.uk/life-style/life/826816/male-pattern-baldness-cure-hair-loss-treatment
    87% of people said they’d do this fat injection deal I did the vote at bottom. I personally would not do it and feel like it’s these half a** treatments that are hindering the real progress in hair loss research. People waste their money on this stuff and companies and doctors think “hehe jackpot! but it doesn’t do anything in fact one photo I think the guys bald spot definately got bigger.

      1. But don’t some people who suffer from AA also suffer from mpb? So what if 100% of the male subjects fully recover hair? This trial may actually verify more than just its itended purpose.

        1. They claim topical may work for AGA, but not oral. Need topical trial once correct topical formulation is created.

          Plus needs to be selective JAK 3 inhibitor.

        1. You shave ur head take a picture grow it out an inch take a shot in the right lighting it looks like an amazing before and after. Go ahead go for it man just saying there’s no regrowth there and if there is its peach fuzz

  15. Why do people think Shiseido will release something in 2018? They’re not even half way don’t their 3 year trial, unless I missed something?

    1. Shiseido and replicel have both said they will be at market in 2018… then it turned into they will have finished all trials and made major announcements at end 18 and thus be at market 2019….

  16. I agree with egghead those before after treatment is a joke. They can’t say they can cure mpb when their before after pics show otherwise. I see no difference. You should loOK at a before after and be like “sht! That is amazing, his whole hairline is restored or oh man! His crown is completely filled in! Amazing! Not us zooming into the picture to find a stray new hair sprouting out lol. Sad just sad they still pull these scams on us.

  17. Curis Inc was another company that had it on their product pipeline, I even got stocks from them. Same problem, they decide to not enter into phase 2 cause side effects from phase 1. Basically, forget about Sonic

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