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[John Difool]

Those who have been months with Pegasus protocol (Ru, estriol , SW , way , chir ect.... , not including SAG) are having regrowth or al least stop hair loss ¿?

Yes but how many of us there are?

 

[pegasus2]

HI pegasus2,
I'm thinking about adding SAG to my protocol for a diffuse thinning Androgenetic Alopecia, but my point is about dosage, schedule and, in turn, cost, efficacy, safety.
How did you come to the dosage for SAG of 0.15%, 2 ml per day? Is it coming from your contacts that used it in the past?
In the study on mouse model, they used a really low concentration of 0.6 microg/microL and 25 microL solution in acetone 95% and DMSO 5%, even at single dose ,on an area the looks like 3-5 cm2. Induction ramped up for 5 days and lasted at least further 5 days. The authors commented they think there was a sort of lag for Shh induction due cell activation; SAG didn't go systemic.The same study run a test on excised fetal skin, daily application, % increased up to 0.15 microg/microL, but 8 microL and unknown air exposed area, nor the dosing rationale has been argumented.
But you have reported SAG EC/I50 curve, also with cyclopamine as inhibitor,showing a gauss-like behaviour, with inhibition of the activation at microM concentrations. As speculation for dosage, I have googled for mouse skin thickness and found something like 0.5 mm vs the 2.5-3.5 mm of human scalp skin, so factor 5-6X.
This is my math as backcalculation of the dosage of 0.15%, 2 ml.
They used approx 5 microL/cm2 ,15 microg total dose, so 3 microg/cm2
By assuming factor 5.5 because of human skin thickness, 150 cm2 application area, the dose would be 3X5.5X150=2475 microg, so 2.5 mg or 2 ml at 0.125%.

What is the reason for using it more than once in a 2 weeks Follica-like protocol?

Curis used Hh-Ag 1.8 in their study, which is more potent than SAG, but I couldn't find exactly how much. SAG is Hh-Ag 1.3. I would have to dig up the information on exactly how much more potent 1.5 is versus 1.3, but iirc potency is at least 3-fold higher with 1.5. There's also some data on concentration in the Cotsarelis patent below that I went by, but I can't find my notes for that right now.

The patent says SAG should be administered on days 5-8 post wounding, which is what I follow. I've tried various other regimens but I settled on only pwd 5-8. High Wnt signaling late during wound healing inhibits hair growth. Shh overcomes that inhibition, so you don't need to time Wnt signaling exactly right. As you noted, Shh targets stay elevated long after application, if the timing in mice translates to humans then pwd 5-8 is sufficient.

COMPOSITIONS AND METHODS FOR TREATING HAIR LOSS - The Trustees of the University of Pennsylvania

<div p-id="p-0001">The present invention provides methods for treating hair loss, treating, inhibiting, or suppressing a degenerative skin disorder, treating androgenetic alopecia (Androgenetic Alopecia), generating ne

www.freepatentsonline.com

 

[MrOscar]

Thanks. It is not the easiest patent to be read...
Fig. 30 says 10 nM Shh agonist. The text says subcutaneous injection 5-8 PWD. It is weird they applied that sort of mesotherapy for the agonist administration, also because by googling I see subcutaneous injection make a sort of flat sachets. Volume for each one should be 50uL and we might assume one injection per cm2 or less, so it could be a sort of "1:10 dilution" into the target tissue.
Potency: here they say"In a particular embodiment, the SHH agonist is Hh-Ag. Hh-Ag (also known as Hh-Ag1.5) is a small-molecule chemical agonist of Smoothened (Smo) receptor and is an activator of sonic hedgehog (Shh) signaling. It is derived from an initial synthetic hit compound “Hh-Ag1.1”, and optimized to achieve the activity IC50=1 nM for agonist activity. This molecule is commercially available for research use and being sold by Cellagentech, Inc. Its molecular formula is C28H26N3OS, CAS number is 612542-14-0, and chemical name is 3-chloro-4,7-difluoro-N-(4-(methylamino)cyclohexyl)-N-(3-(pyridin-4-yl)benzyl)benzothiophene-2-carboxamide."

If the above guesstimate is right, they were targeting IC50 on daily basis.

The topical lotion with SAG in the mouse study seems pointing to 100 nM final concentration in the receiving tissue.
I don't know if putting the Shh agonist that way in sequence for 4 days could cross the border of inhibition area.

I'm looking at the patent on the smartphone. Am I missing some other info in the patent?

I want also to thank you for sharing your experience. I'm using estriol 1% 2ml /day 10 days /14 days cycle. Procured it after reading this very inspiring thread (got it from the same seller you have used, USP grade).
Something seems moving on the hairline and the mid area looks thickening. For sure I can say the skin reacted quickly to estriol as, after mild flaking for a couple of days, it became very smooth in the temples area and forehead. I see also some smoothing effect on the forehead wrinkles.No sides so far, after 2 months on it.

 

[pegasus2]

Curis applied it daily in the mouse study for I think about one week, and got the same response as they did with a single dose, so at least in that case daily doses weren't crossing over to inhibitory. In the studies done by Cotsarelis with Hh-Ag 1.5 they used two or three different concentrations, but I don't recall the details. EC50 for SAG is 3nM to 10nM, so that's 3-10 times less potency.

I think estriol was more effective for me than 17b-estradiol. The latter only seemed to make me shed. I'm glad it's working for you too.

 

[John Difool]

You can always use Estriol and Estradiol as long as you place enough time between the two as their half life is quite short (a couple of hours). So perhaps Estriol am & pm and Estradiol at noon?

 

[wislow9]

Yes but how many of us there are?

I have to get chir and SW ... , at the moment I´m with the rest
SAG protocol is more complex and risky

 

[Xenophon]

Most of the minoxidil sides are probably mediated by upregulation of PGF2a.

I had terrible facial bloating when I was using topical minoxidil 4 times a day. I didn't get it as badly from oral minoxidil, but I was using a diuretic along with it. PGE2 or minoxidil, pick your poison. I wouldn't even hazard a guess as to which one will be worse on your skin.

.25mg is nothing. I doubt that doctor is seeing better results with that than 5% topical except in topical non-responders.

any update on reversal of oral minoxidil sides @pegasus2 ?

I just looked at some photos of my forehead about 3 months apart while I've been on oral min. it's official, my skin looks like sh*t. It's hard to describe exactly how it's just like less youthful, less consistently colored, and like less voluminous. Forehead veins are more pronounced etc. Starting to think about getting off it also. I don't feel like I ever responded topical minoxidil though, would you say you were a topical min responder?

Also probably doesn't help that a couple weeks ago I added PGE2, SW, and PGF2A to my topical. By the book that combo should be pretty terrible for skin correct? Just want to know what I'm getting into.

Having used minoxidil on and off, I have confirmed now over the past couple years that I can't really maintain a good facial texture on it. It seems to kind of dry out and lose collagen right away. I will notice this problem in the gym mirrors with the bad lighting. I start to look like Sting, only without the catalogue of adult rock treasures (yet). I supplement colllagen ever day and use a dermapen on the face. I find its effects very fleeting on the face, but because it brightens you up a good deal every fortnight, I tend to think this can slow aging a good deal.

In spring I switched to Reviv hair serum with the gray reversal and triaminodil (sp) added. So it has all the necessary components for mild cases like mine with a prior FUE done. Nothing has changed with this, good or bad. No reason to change products then for another year or so.

 

[theotherusero]

Unfortunately eplerenone is barely soluble in DMSO so I haven't bothered to use it topically yet. I think it would be quite potent topically. Hopefully we can get finerenone soon, it's more potent than eplerenone, smaller, and more soluble.

Epleronone also inhibits collagen production, so I stopped taking that orally as well. I'm using 5mg/day topically.

What vehicle do you use for topical Epleronone?

 

[Capone]

Having used minoxidil on and off, I have confirmed now over the past couple years that I can't really maintain a good facial texture on it. It seems to kind of dry out and lose collagen right away. I will notice this problem in the gym mirrors with the bad lighting. I start to look like Sting, only without the catalogue of adult rock treasures (yet). I supplement colllagen ever day and use a dermapen on the face. I find its effects very fleeting on the face, but because it brightens you up a good deal every fortnight, I tend to think this can slow aging a good deal.

In spring I switched to Reviv hair serum with the gray reversal and triaminodil (sp) added. So it has all the necessary components for mild cases like mine with a prior FUE done. Nothing has changed with this, good or bad. No reason to change products then for another year or so.

Yep minoxidil works but it’s a shame it turns me into Mick Jagger

 

[pegasus2]

What vehicle do you use for topical Epleronone?

DMSO. You can't dissolve much.

 

[Pls_NW-1]

Wow! Insane recovery? Is it possible for you now to leave everything and continue with AAs? Topical RU and oral Duta? Just for maintenence!?

Also... I have a few questions. Can I PM you?

 

[pegasus2]

Wow! Insane recovery? Is it possible for you now to leave everything and continue with AAs? Topical RU and oral Duta? Just for maintenence!?

Also... I have a few questions. Can I PM you?

That's what I'm been doing atm, and so far it is working out.

Sure, I don't mind

 

[Pls_NW-1]

That's what I'm been doing atm, and so far it is working out.

Sure, I don't mind

I can't understand whats RSPO2/3 and what it has to do with hair loss. Kinda new to this topic.

I have some questions which Im going to ask in the evening gotta still figure out some things. But this seems to be legit, right?

Side note: Im 17yo and my hair started to thin badly for a year or even 2. Think finasteride will act like a candy for me lol

 

[John Difool]

DMSO. You can't dissolve much.

Solubility: DMSO: 2 mg/mL, clear (warmed)

 

[John Difool]

RSPO2/3 are proteins that maintain Wnt signaling, which is what makes hair grow.

17 is a little young for finasteride. You haven't finished maturing yet.

Unless you are transitioning, you should wait for that.

 

[Pls_NW-1]

RSPO2/3 are proteins that maintain Wnt signaling, which is what makes hair grow.

17 is a little young for finasteride. You haven't finished maturing yet.

Ok and those proteins are where!? Ig thats the chemical WAY...? Right?

 

[Tom4362]

Ok and those proteins are where!? Ig thats the chemical WAY...? Right?

I would first finish biology101 if I were you bro

 

[xaragedom]

Very compelling results But why you decided to choose PGE2 over latanoprost? Isn't latanoprost more effective and stable in solutions? Or others analogues of PGE2 or PGE1 (like misoprostol) since PGE1 activate PGE2 receptors anyway. Bioidentical prostaglandins have shorter half-life in vivo (and in vitro) than analogues.

 

[pegasus2]

Very compelling results But why you decided to choose PGE2 over latanoprost? Isn't latanoprost more effective and stable in solutions? Or others analogues of PGE2 or PGE1 (like misoprostol) since PGE1 activate PGE2 receptors anyway. Bioidentical prostaglandins have shorter half-life in vivo (and in vitro) than analogues.

Dinoprost is basically the same thing as latanoprost. PGE2 and PGE1 may bind to the same receptors, but they exert opposite effects on them. PGE2 is more potent, and it's stable enough to last two weeks in non-aqueous solutions, which is all I need.

 

[Charger]

Is it a given that the scalp will turn pink when using PGE2? I've only applied twice so far but I haven't really noticed this effect, has me wondering if my stuff is bunk.

@pegasus2