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Curis, P&g, And The Lost Baldness Cure

Discussion in 'New Research, Studies, and Technologies' started by pegasus2, Mar 20, 2020.

  1. pegasus2

    pegasus2 Senior Member My Regimen

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    Many of you have heard of this drug before. Famous hair loss researcher Angela Christiano has said that it cured hair loss, but caused skin cancer. The drug in question is a variation of SAG (smoothened agonist). It seems much information on this project has been lost over time. I hope we can piece it together in this thread. People lost interest in it due to the risk of cancer, but if there is ever going to be a pharmacological cure I believe it's going to come from finding a way to safely manipulate this pathway.

    The role of the sonic hedgehog (shh) pathway in hair follicle cycling and morphogenesis was revealed in the late 90s. Then in 2005 Curis published this paper that set the hair loss world abuzz:
    https://www.sciencedirect.com/science/article/pii/S0022202X15324830

    Shortly after publishing that paper Curis partnered with Proctor & Gamble to develop an shh agonist for treating male pattern baldness. They successfully cleared the first of two preclinical milestones with P&G before the partnership was terminated because, "the Hedgehog agonist compounds under development pursuant to the collaboration did not demonstrate an acceptable safety profile". Curis announced that they would seek out another partner for developing the drug, but they either abandoned that idea or were unsuccessful in finding a new partner.

    https://www.businesswire.com/news/h...hes-Preclinical-Milestone-Hair-Growth-Program



    Now this study has recently come out showing that tumors regress considerably with one week treatment of shh inhibitor vismodegib while new hair follicles remain intact:
    https://elifesciences.org/articles/46756

    What if the shh pathway was activated just long enough for HF morphogenesis to begin, and then vismodegib was applied for a week. Would that be early enough to prevent any tumors from forming in the first place?

    I found some interesting posts from a member on this site with the handle "hedgehog_info" who seems to have been connected with Curis. He joined the forum when the partnership with P&G was announced, and then left when the partnership was terminated. His final post:
    Here are some other interesting posts that I found:



    This drug was apparently tried by four members of one of the private forums more than five years ago. Reportedly they all regrew hair, but I don't know how much. I wonder if anyone here has seen the pictures, or can get in touch with these people? It's been over 5 years now. It would be nice to know if any of them ever developed any tumors. Maybe they are all dead now? As far as I know nobody else has ever tried this drug for hair loss, and for good reason.
     
    #1 pegasus2, Mar 20, 2020
    Last edited: Apr 9, 2020
  2. Armando Jose

    Armando Jose Senior Member My Regimen

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    Very interesting,
    I have always thought that you should only use any drug that tries to promote hair growth only for a period of time and not for chronic use. The reason is that human hair is out of sync, and that each phase of the hair cycle can vary its dependence on that drug.

    An example is minoxidil/finas sheding/regrowth phases.

    Take care and good luck.
     
    pegasus2 likes this.
  3. S Foote.

    S Foote. Experienced Member

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    There is a major influence upon hair follicle enlargement that is being overlooked in the current research, and explains why some effective treatments like this can grow a lot more hair, but also risk cancer development. All normal cell growth and tissue development is subject to the external resistance based spatial grow controls described here. http://phys.org/news/2014-04-room-tissue-growth-cell-response.html

    This consideration is a central concern in tissue engineering where the goal is to grow new tissue in the body. This is why scientists in tissue engineering use scaffolds to negate this external resistance factor, and create the intended size and form of the required new tissue. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587658/

    To encourage new tissue growth is also the goal in hair loss treatments, yet this research consistently fails to take account of this overruling growth control. This is technically grounds for the retraction of many papers that propose hair loss treatments for quote, "Ignoring a process that is known to have a strong influence on the area under study" https://authorservices.wiley.com/Re...-by-step-guide-to-reviewing-a-manuscript.html

    The evidence is that this external resistance based growth restricting factor, is the significant mechanism of the miniaturisation of hair follicles in the common cases of hair loss. Foote, J Tissue Sci Eng 2018, 9:1 DOI: 10.4172/2157-7552.1000217 If this is so, any treatment that can enlarge the follicles against this external restriction, will risk uncontrolled cell growth and cancer development. I suggest this is what is happening here.

    The primary influence of this growth control upon anagen follicle growth, also explains why the cell based treatments continue to fail when it comes to actual Human trials. You cannot just inject a cocktail of cells, primordiums or whatever, and expect this to grow a large hair follicle against this growth restriction. The accepted science in tissue engineering says otherwise.

    The only way to grow large hair follicles that last long term, is to deal with this external resistance factor. There is nothing in the pipeline that is going to do this. The whole focus of hair loss research needs to change.
     
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  4. Throwaway94

    Throwaway94 Established Member My Regimen

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    Oh 2005... I was but a wee 10 year old laughing at my dad's bald spot.

    The idea behind most of these cell based treatments is that they are resistant to the external resistance factor, aka the biopsies are taken from the donor zone. If these cells /primordiums / whatever don't assimilate as planned and retain DHT resistant hair then yeah it's back to the drawing board.
     
  5. Armando Jose

    Armando Jose Senior Member My Regimen

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  6. dr75

    dr75 Established Member My Regimen

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    Very interesting thread. Please keep us updated.
     
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  7. S Foote.

    S Foote. Experienced Member

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    Leaving the question of any significant direct influence of DHT on hair follicles to one side, the fact is that all normal tissue growth can be prevented by a certain degree of external resistance. No "normal" hair follicle growth is immune to this, DHT resistant or not. Only cancer cells can avoid this.

    When you factor this into the whole body of data about changes in hair follicle size, it becomes clear that spatial conditions are playing a central role here, and that the hair cycle evolved to use the prevailing tissue pressure conditions to adjust anagen follicle size. This had important purpose in the evolution of hairy mammals. I have uploaded my take on this here.

    The Holy grail of hair loss treatment, is to get the miniaturised follicles to significantly re-enlarge. In this regard, I think the immune deficient mouse study here is very important. DOI: https://doi.org/10.1067/mjd.2003.95

    This clearly demonstrated that Human miniaturised hair follicles, have the internal ability to significantly re-enlarge given the right external conditions, despite any direct action of Androgens.
     

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  8. HairOnFire

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    A more conventional take: The purpose of hair follicle cycling is to prevent hair from becoming too long. Unchecked growth of hair would be a major hindrance for haired animals. A mouse with 6-inch long hair would be conspicuous, and all that hair would also reduce it's ability to squeeze through very tight spaces. Male lions would trip over their manes. Humans with foot-long eyelashes would have trouble seeing. Etc.
     
  9. Armando Jose

    Armando Jose Senior Member My Regimen

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    More important than follicle cycling in humas is its asynchronocity of scalp hairs, all hairs are renovated withouth loss of personal image. Think about it, what would happen if all humans shed scalp hair at the same time !!!???

    OTOH, Mr Foote is very persuasive and he is right regarding spatial conditions and hydrahulic forces surrounding pilosebaceous unit.
    "Any secreting gland must have arrangements for an excess of local tissue fluid, as the raw material for the required secretion"
    My idea is that sebum have a role, because t s and fluid and it is inestabe passing the time, changing ts rheologcal properties, also its composition and redox state, and can possibly can explain the pattern of hair loss in common baldness,
    A paper of Masako Nakamura in J Soc Cosmetic Chem Japan vol 27, nº4 1994
     

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  10. baldingAF

    baldingAF Established Member My Regimen

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  11. baldingAF

    baldingAF Established Member My Regimen

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  12. baldingAF

    baldingAF Established Member My Regimen

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    Our scalp environment's standard through 17B hydroxysteroid and other dehydrogenases has favored overproduction of androgens, that coupled with sensitivity is my reasoning/theory. This synthesis starts with cholesterol. whether its an increase of certain enzymes, lack of others, influence from serum or something along those lines it comes down to steroidogenic communication and getting the right players involved.

    your metaphor is dumb
     
  13. baldingAF

    baldingAF Established Member My Regimen

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    but yo daddys daddy and them eggs is huge for the scientific community. kudos Dr.
     
  14. baldingAF

    baldingAF Established Member My Regimen

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    lol heres a breakdown for you and im done. daddys daddy = your father's father = your gradfather

    him eating eggs = not a damn thing to do with not going bald

    your thought process = fuel for MTV
     
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  15. pegasus2

    pegasus2 Senior Member My Regimen

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    I'm talking about your post above it. You have very poor communication skills. I mean grade school level, bruh. It reads like you're saying cholesterol causes baldness. I'm not one to use anecdotes, but if you're going to propose a retarded theory then an anecdote is all it's worth in response. Go ahead and create your own thread about how lowering cholesterol will save da hair bruh. :rolleyes:
     
  16. baldingAF

    baldingAF Established Member My Regimen

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    Goodness gracious. You do know that cholesterol is the precursor to like every major hormone right. all these natural steroid and their effects, including the dht you mentioned, start at cholesterol right. You must know that to have any kind of basis here.

    DHT, testosterone, estrogen -> they all come from cholesterol. Sorry for not making it easly understood to the layman, thought I was talking to people that understood more than just what they've been told.

    Locally or systemically that chain is influenced by enzymes but they need the precursor(s). To focus on the end and not take the whole picture into account leads to doo doo treatments. Theres a whole system at play, not one or two. So we start at the source and work from there. And according to your reasoning for this post, the absolute source for hormones (CHOLESTEROL) coincides with your theory. But you too busy trying to stand on shoulders than actually learn something- something extra basic at that. you've been labeled.
     
  17. baldingAF

    baldingAF Established Member My Regimen

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    *Explains science theory with some science words

    Mythical Flying Horse that came in second: you don't know how to communicate cause i don't understand those words

    *Explains base concept in laymans terms

    Mythical Flying Horse that came in second: You must be on drugs AND LIKE VEGETABLES!!!!! HAHAHA I am the best and my posts are as mythical as my handle on this forum. Can't wait till I can laugh about this with my body pillow of dog the bounty hunter later!! HAHA
     
  18. pegasus2

    pegasus2 Senior Member My Regimen

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    Ignorance is bliss I guess. Must be fun going through life thinking you're smart with that double digit IQ.
     
  19. baldingAF

    baldingAF Established Member My Regimen

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