Curis, P&g, And The Lost Baldness Cure

[Sweuser]

What are you basing your concernes of cancer on?

Have you found any real trials with shh inducers that increases the risk, or are you just concluding from mutated shh pathway genes in some cancers?

There still needs to be a few more functional mutations before it can turn into cancer. And I've never seen any evidence of shh mutations to increase the risk of more mutations.

I'm not sure what the risk is, but It's probably a good idea to be carefull when It's something new. And likely good to stay away from sunlight.

 

[Photon]

I wonder how a diffuse thinner like myself will do with this treatment. The bad thing is that I have to apply on my entire scalp, same with minoxidil. So that might actually increase the risk of cancer, what do you think?

 

[pegasus2]

What are you basing your concernes of cancer on?

Have you found any real trials with shh inducers that increases the risk, or are you just concluding from mutated shh pathway genes in some cancers?

There still needs to be a few more functional mutations before it can turn into cancer. And I've never seen any evidence of shh mutations to increase the risk of more mutations.

I'm not sure what the risk is, but It's probably a good idea to be carefull when It's something new. And likely good to stay away from sunlight.

There are no real human trials that we have data on. There are mouse trials. No one knows the degree of the risk, but there is a risk. I'm not going to sugarcoat it and make people think this stuff is candy.

constitutive activation of Hh signaling has been implicated in the development of numerous forms of cancer. It is unclear whether the therapeutic effects of prolonged Hh agonism can be separated from the detrimental effects commonly linked to tumor formation; however, the ability to decouple these activities is crucial to moving this class of compounds forward.
https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.201300358

In the absence of mutations, particularly in Ptc, you have less to worry about. That doesn't mean you can't still get cancer.

If people do want to try it they need to be careful. It's a good idea to have an shh inhibitor on hand, and avoiding UV exposure is good advice as well. They need to do it under a doctor's supervision as well.

If you're going to get SAG, but you can't afford it, purmporphaine is similar and substantially cheaper.

It should work for anyone, but if you have cancer a Hh agonist is going to act like miracle grow on it. Hopefully anyone who does try it will share their experience here.

 

[Sweuser]

That's probably a good approach!

I did some search in the literature, like you've probably done extensively, concluding what you're referring already:

Mice transfected with a mutated gene in HH pathway TOGETHER with one more oncogen can show cancerous lesions. But I have yet to see any in HH pathway alone, that would indicate precancerous cells..

I'm very tempted to try this myself. Are you willing to share your source? You can send me in dm.

 

[John Difool]

I wonder how a diffuse thinner like myself will do with this treatment. The bad thing is that I have to apply on my entire scalp, same with minoxidil. So that might actually increase the risk of cancer, what do you think?

You don't have to start this treatment by splashing the whole scalp. Try to be hyperlocal with your temples first (assuming they are gone.) And since results are pretty fast you can go from there after one or two cycles.

 

[wislow9]

Very interesting this post , but which drug are yourselves trying .... ? and which is the SAG CAS ¿?
https://www.selleckchem.com/products/smoothened-agonist-sag-hcl.html is that ¿?

 

[pegasus2]

Very interesting this post , but which drug are yourselves trying .... ? and which is the SAG CAS ¿?
https://www.selleckchem.com/products/smoothened-agonist-sag-hcl.html is that ¿?

Either one of the following, it doesn't really matter. Top is free base, bottom is salted:
CAS 912545-86-9 Somewhat less stable. Doesn't matter since you're probably not mixing more than one dose at a time.
CAS 364590-63-6 Somewhat higher molecular weight >500 daltons. This could be a factor if you're not wounding before application.

Also, purmorphamine CAS 483367-10-8

 

[GroLocks]

Clobetasol & Halcinonide have also been identified as moderate Smo agonists. They have been used with Alopecia Areata patients. I would think combining one of these w/ needling + tretinoin + minoxidil might result in hair growth. Of course, this would also be potentially risky, as with SAG. There are no studies or data w/ human trials, other than Alopecia Areata patients using single drug application. Here is a comparison of potency of Clob & Hal & SAG as Smo agonists. Clob & Hal are readily available drugs. (They are high level corticosteroids)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889058/

 

[pegasus2]

Hair growth is a side effect of halcinonide. It's been known for a long time that those drugs grow hair, and have a good safety profile too.

Although while SAG can overcome BODIPY-cyclopamine in human embryonic kidney cells the others can't.

I don't think that study is a really good comparison of the efficacy of any of these drugs in any particular tissue, it just shows that these 4 GCs can act on Smo.

 

[wislow9]

Either one of the following, it doesn't really matter. Top is free base, bottom is salted:
CAS 912545-86-9 Somewhat less stable. Doesn't matter since you're probably not mixing more than one dose at a time.
CAS 364590-63-6 Somewhat higher molecular weight >500 daltons. This could be a factor if you're not wounding before application.

Also, purmorphamine CAS 483367-10-8

I understand then that Purmorphamine is another cheapest identical option ....
How many times at week are using SAG ¿? Are using Vismodegib ¿? mixed with SAG ¿?

Do you think that use SAGS may be a problem in people with hair transplant ¿? more cancer risk ....... ¿?
Also , It would be interesting to know if SAGS could make regrowth the donor area follicles extracted in a hair transplant ...

We could send a email to Angela Christiano for more information ....

 

[GroLocks]

@pegasus2 - I don't disagree with your comments. My point in posting about them, was that they (Clob & Hal) do act as Smo agonists, they do displace BODIPY-Cyclopamine. Certainly not to the degree that SAG does, but, about 20-25%. That may be enough with the help of minoxidil, needling, tretinoin (to mitigate the skin atrophy from glucocorticoids). The combo may activate Hh just enough, over a period of time, to initiate hair growth. The only citation I could find using the combo triamcinolone acetonide after micro needling was in a patient with Alopecia areata, and, it did initiate regrowth of hair after 2 sessions. TA has been shown to bind to Smo & enhance Hh signaling. Even though the "small molecule" Class glucocorticoids have been shown to activate Hh, I don't think it is enough by themselves to trigger hair growth. What they do have is a history of use in humans & a safety profile. The combo (Hal / minoxidil / Needling / Tretinoin) might be enough to over-come the remaining inhibitors at play. Taking into consideration of course, the feedback loop of Hh ... too much stimulation triggers shut-down. How much is too much? .. not enough data yet. Once a week session might be right ... once a month session might be right. I am starting this protocol currently @ once a week. I will update if there are positive / negative changes.

 

[pegasus2]

@wislow9 Purmorphamine is not identical, it's similar. They are both Smo agonists and seem to have similar pharmacokinetics. They both act on the same cells as far as I can tell, so they might work the same way on hair too. Purmorophamine is not a part of the benzothiophene Hh agonist class that SAG belongs to, which is the type used by Curis for hair growth. My guess is it works just as well, but at a higher dose. I don't know which one is worse for side effects as neither one is targeted.

@GroLocks I agree, I think halcinonide in particular is an option for people to consider. It's a safety-tested alternative to SAG and purmorphamine. Shh is downregulated in balding scalp, so whatever is inhibiting it likely won't be nearly 100% overcome by these GCs if cyclopamine isn't, but you could still get some regrowth. Does anyone here have a clue what is inhibiting Hh in our scalps?

A small dose of tretinoin can be helpful for hair anyway. I wonder what effect the cell turnover rate would have on the cancer risk with SAG.

Keep us updated on your regmin. Do you have a link to that AA case study?

Edit: I forgot to add, vismodegib is an shh inhibitor so it doesn't make sense to mix the two together. However, in this study they created new follicles in Ptch1-null mice via supraphysiological Hh signalling. Naturally, in the absense of Ptch1 tumors formed along with the new follicles. After new follicle and tumor formation they applied vismodegib. Tumors regressed, but the new follicles were unaffected. This new hair should be permanent as long as you have DHT under control. I don't see what difference a hair transplant would make as far as risk goes.

 

[John Difool]

I understand then that Purmorphamine is another cheapest identical option ....
How many times at week are using SAG ¿? Are using Vismodegib ¿? mixed with SAG ¿?

Do you think that use SAGS may be a problem in people with hair transplant ¿? more cancer risk ....... ¿?
Also , It would be interesting to know if SAGS could make regrowth the donor area follicles extracted in a hair transplant ...

We could send a email to Angela Christiano for more information ....

I will use SAG forthnightly after wounding ala Follica. No Vismodegib yet and hopefully never. It's a safety gate to treat skin cancer.

I looked at your regimen and from doing simply RU to jumping on Shh agonists like SAG is a totally different ball game. Do you understand this?

First recommendation would be to try anything else before using SAG due to cancer risks. There are many other drugs that will give you opportunities to find out if they work on you starting with Fina Duta minoxidil Nizoral etc

As for regrowth in donor area, sure why not. Unless you had a big scar with FUT or many scars on FUE which will make those areas of the scalp harder to manage but the OP talks about this somewhat.

You are welcome to shot an email to Christiano but I doubt she would bother replying. Do you really believe she would advise you on how to take these dangerous off-the-market drugs without risking her job? I know a few people who would like to become a rat in her lab but that won't happen. They have mice for running their experiments.

 

[pegasus2]

Yeah, it's hard to believe you could be willing to try this, but not dutasteride. I mean dutasteride has 10 year safety studies and never killed anyone. We don't have any safety studies on this. Talk to your doctor and ask him which one you should try. I guarantee you it will be dutasteride.

 

[GroLocks]

@pegasus2 - Triamcinolone Acetonide + needling https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996798/ & https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996797/
As for using Tretinoin with SAG. I would be very careful. Tretinoin as you indicated speeds up cell replication. It also increases stratum corneum permeability. And, can be an irritant. The first one, might be advantageous, but, the other two not. I am using it w/ glucocorticoid (calms irritant factor) & the tretinoin counteracts atrophy of skin. Neither of those would be a factor w/ SAG (w/ my limited knowledge of SAG).

 

[pegasus2]

@pegasus2 - Triamcinolone Acetonide + needling https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996798/ & https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996797/
As for using Tretinoin with SAG. I would be very careful. Tretinoin as you indicated speeds up cell replication. It also increases stratum corneum permeability. And, can be an irritant. The first one, might be advantageous, but, the other two not. I am using it w/ glucocorticoid (calms irritant factor) & the tretinoin counteracts atrophy of skin. Neither of those would be a factor w/ SAG (w/ my limited knowledge of SAG).

Since I'm needling before applying SAG permeability isn't an issue. lol I'm actually going to start wating a day after I needle to apply SAG, but I'm not considering tretinoin anyway.

 

[John Difool]

I am using RetA 0.1% & Beta & Keto cream once a day. I'll be careful.

 

[GroLocks]

@pegasus2 - If you haven't used tretinoin before, I would use a small amount on the other temple area (assuming you are only using SAG in one small area at the moment). Within 2-3 days of tretinoin gel (lowest concentration) first application, you will likely get red & irritated in that area. This will give you an idea of the effect you'll get. You can then decide if you really want to use it on the SAG temple. Once an area is irritated, you'll have to stop using anything in that area until it calms down. It will also likely peel. Might even have to use a bit of hydrocortisone to calm it down. And, the reservoir effect of tretinoin I believe is 3-4 days. Eventually, your skin will develop a resistance to the irritation, and, won't get as irritated. Even if you're only going to use it once a month, I would first test it on the non-SAG side. Also, if you do use tretinoin, don't go out in the sun without some kind of sun screen. Tretinoin makes your skin very vulnerable to uv radiation.

 

[John Difool]

The way I dealt with the irritation part was to start at 0.01%, then 0.05% then 0.1% in the lapse of 3 months. At first skin felt raw then pilled off for a few weeks. I am passed that now. Don't use if you have a tendency to develop Eczema.

 

[John Difool]

Actually not just Tretinoin makes skin sensitive to uv rays. When using SAG wear a cap on your head if you want to live.