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.
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.
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"This first preclinical milestone represents the successful completion of several initial steps toward our goal of bringing a topical Hedgehog agonist into the clinic for the treatment of hair growth disorders," said Daniel R. Passeri, President and Chief Executive Officer of Curis, Inc. "We are pleased by the progress that the joint research team has made, particularly since our collaboration with Procter & Gamble began only five months ago. We are hopeful that this will be the first of several development achievements that will allow Curis and Procter & Gamble to advance a Hedgehog agonist into clinical development and ultimately succeed in providing an effective treatment for hair growth disorders."
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:
Yes I believe the 14 day tox study had side effects. The program will revert back to curis to develop if they want to reformulate the topical application. Wouldn't expect them to do this anytime soon.
Here are some other interesting posts that I found:
hedgehog_info said:"P&G uses the same animal strain and got the same results as curis did before they partnered for this program."
"Side effects to this treatment is the real question if the FDA will allow this Hh agonist treatment to work. It will definitly not be an over the couter medication."
"I hope it works too. I honestly have doubts due to cancer risk effects. Not that it won't grow hair."
"The male hormone slowing the hair back down, the immune system attacking " something" about the miniaturizing follicle that eventually causes cell death in the lower follicle. Perhaps hedgehog could be a treatment that has to be applied once a year? "
"When the Hh is turned on it actually prevents the immune system from attacking the cell sorta of like cancer cells aren't seen by the immune system. However, it will be a once applied application and hopefully quick at that. I would guess application's would really depend on how fast your hairs fall back out and doesn't grow back."
"It was orginally going to be used for chemo therapy patients. However, curis along with P&G thought they could bring it to the market for male pattern baldness."
" on the flip side they have done animal experients and have noted these same cells that send the signals when turned on permanately develop BCC and other types of skin cancer.
Curis is trying to turn on this pathway just enough to grow hair but not have patients develop cancer.
I little inside info. Curis was trying to develop another program for stroke
but use a systemic agonist of this pathway and one of the side effects they found was hair growth with a one time application."
"Yes you would have to apply a Hh agonist treatment every few years. However, it really depends on how fast it falls out."
"The pathway is only turned on for a day(or less) in order to start the wave of 2ndry pathways to start the hair growing.
If the pathway is turned on to continuous you will get Basal Cell Carcinoma (skin cancer), or if it turned on more frequently then normal you might get a mole with a long hair sticking out of it."
"Yes if you turn on the pathway to much you could develop a lot of problems. Curis/P&G have not noted any side effects after 1 year of a one time topical application treatment. But there is a big chance for side effects and should not be taken lightly.
For example this is not going to be an over the counter answer to for hair growth. It WILL work for hair growth but we will see what the FDA will say.
Not trying to pessimistic but there are some REAL things to consider. I hope it works and I think P&G developing this says a lot and bodes well for clinical trials.
Agonists of the Wnt pathway probably won't be used for Hair growth unless they are using Embryonic stem cells to create new hair follicles."
"about a year until human trials. Until then P&G are getting the formulation and process development aspects of the drug correct."
"I would say that a Hh agonist treatment for Hair growth would be whenever the hairs shed again."
"New presentation but nothing has changed. It is all up to P&G. They should select a lead molecule in Q1 of 07 and then an IND late in 07."
"Yes that would be a perfect world. I myself work at a biotech company and can saw it costs a lot of money and resources to get a single drug into the first patient. Even then a lot of them fails before reaching the public."
"Go ahead and PM me or send me an email and I will loan you the article.
hedgehog@pathway2curis.com"
"The Wnt pathway along with a few other embryonic pathways help to create a hair follicles from immature cells. So if somebody’s hair follicles died then you would want to create hair follicles this is the route to take. I guess it is sort of like HM but would probably be a lot faster.
The Hh pathway (Wnt’s sister pathway), does not create new hair follicles rather it kicks any hair follicles into the growth phase. Such as in Alopecia. This is what Curis along with P&G are hoping to do. At first they were seeking to develop this treatment for patients with chemotherapy when their hair fell out. However, they both think now that they can develop it for Alopecia and other hair follicle cycling problems.
Both of these pathways when turned on for an extended period of time WILL cause cancer. About 1/3 to ½ of all cancers have these pathways turned on abnormally. I honestly don't think that a topical application will cause a pathway to be turned on continuously but you have to use caution.
It should also be noted that Wyeth pharmaceuticals are developing a Hh agonist for stroke patients. This treatment will use a oral Hh agonist which IMO is more risky then a topical Hh agonist. They have noted side effects in the Oral Hh agonist. The two side effects were abnormal growth in the intestines and hair growth."
"Any body's guess. IND in just under a year. The hair will grow fast but I guess it really depends on how they conduct the clinical trial and how long the FDA wants them to wait to see if any people develop abnormal proliferation."
"Curis product will kick any resting hair follicle into the growth phase. It will be a replacement[to minoxidil] and you probably won't need any other treatment. However, if you have a lot of damage to your hair follicle and it doesn't work well such as maybe a burned victim then you will probably need HM and curis product won;t work. However depending on HM your hairs will probably fall out again and you will need curis's product to kick the HM follicles back into the growth phase.
Regardless of the treatment curis;s product will need to be used every time your hair doesn't go back into the growth phase you have more shedding then growth.
Hope this helps. I don't know that much about HM so i might be wrong on that aspect."
"I believe people with alopecia don't have dead follicles, at least that is what P&G hope.
I would GUESS that people would have to use P&G/Curis treatment every 2-5 years. Their treatment would probably be a 1 time topical application. But this is all a BIG GUESS. All assuming clinical studies go well"
"Hopefully it will be in the clinic in a year and should see results about 10 days after a topical application."
"A few people including P&G seem to think that hair follicle cycling requires a Hh pathway activation to get into the growth. The real problem will be how to stop the side effects."
"There have been a few studies that used a mouse model of hair loss. According to the researchers they said that this animal strain has been extensively studied and characterized for hair cycling, hair loss, hair growth ect... After they applied an agonist (used to turn on the pathway) it grew hair in about 14 days with a one time dose.
They also looked at human scalp and confirmed that we humans also express this pathway when the hair needs to get kicked into the growth phase.
This agonist was going to be first used for people who lost hair due to chemotherapy. However, after curis licensed it to P&G they wanted to develop it for alopecia.
Curis has also stated that neuronal and hair follicles are the most sensitive to pathway activation. Obviously the formulation has to be perfect."
"Well, the pharma companies are betting on a one time application will do the trick. Wyeth is hoping for a one time systemic application (for stroke) and P&G are hoping for a one time topical application. If you have skin cancer and you put this topical stuff on your head it is going to be like adding gasoline to a fire."
"Yes that is the main problem with most of these embryonic pathways. In embryonic development different concentrations of certain proteins will give rise to different types of cells and tissues. For example, high concentrations Hh a gives rise to neuronal tissue, in creation of hair follicles the Higher the concentration of Wnt the more hair follicles develop, however the higher the concentration of Notch less hair follicles are developed.
Also if you don't have the correct concentration of Wnt/notch/Hh to develop hair follicles you will obtain an undesired cell type and thus side effects. My hope that because the Hair follicle is one of the most sensitive types of cells to Hh pathway activation that one could develop a formulation that could potentially develop the target cells. I plan on calling curis in the near future to obtain what exactly the side effects are. IE, undesired proliferation, wrong hair color, hair size, ...ect
The published report from curis didn't report any of these side effects... be interesting to find out."
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.
Last edited: