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Latest research study about AGA & Wnt


#1

a user just posted this on another forum and since I brought up the discussion regarding Wnt & Follica today, this has been a very interesting & affirmitive read.

NOTE: If anyone can upload the entire paper, that would be great!

http://jcem.endojournals.org/cgi/content/abstract/jc.2008-1053v1?papetoc

“Results: Wnt3a-dependent keratinocyte growth was suppressed by the addition of dihydrotestosterone (DHT) in coculture with DP cells that were derived from AGA patients, but growth was not suppressed in coculture with DP cells from non-AGA males.”

Keratinocytes are the key component needed for terminal hairs - keratinocytes Make up the thick hair. This study shows that DHT directly inhibits Wnt dependent keratinocyte growth. This probably is a critical piece of the puzzle. If we can find a guaranteed way of upregulating Wnt signaling, I’d be willing to give it a try. If anyone knows anything about Wnt, please post here so we can discuss further.


#2

» a user just posted this on another forum and since I brought up the
» discussion regarding Wnt & Follica today, this has been a very interesting
» & affirmitive read.
»
» NOTE: If anyone can upload the entire paper, that would be great!
»
» http://jcem.endojournals.org/cgi/content/abstract/jc.2008-1053v1?papetoc
»
» “Results: Wnt3a-dependent keratinocyte growth was suppressed by the
» addition of dihydrotestosterone (DHT) in coculture with DP cells that were
» derived from AGA patients, but growth was not suppressed in coculture with
» DP cells from non-AGA males.”

»
» Keratinocytes are the key component needed for terminal hairs -
» keratinocytes Make up the thick hair. This study shows that DHT
» directly inhibits Wnt dependent keratinocyte growth. This probably is a
» critical piece of the puzzle. If we can find a guaranteed way of
» upregulating Wnt signaling
, I’d be willing to give it a try. If anyone
» knows anything about Wnt, please post here so we can discuss further.

I thought they had already found a way to do that, But it caused tumour growth in the mice.


#3

» I thought they had already found a way to do that, But it caused tumour
» growth in the mice.

That was only because they upregulated too much WNT signalling, and even than the tumors were benign (hair balls under the skin). Look at the ‘puffy mouse’ 1/3 of the way through (and about 80% of the way through - you’ll see the mouse again)
http://www.ascb.org/ibioseminars/includes/player.cfm?name=fuchs&num=2


#4

» » I thought they had already found a way to do that, But it caused tumour
» » growth in the mice.
»
» That was only because they upregulated too much WNT signalling, and even
» than the tumors were benign (hair balls under the skin). Look at the ‘puffy
» mouse’ 1/3 of the way through (and about 80% of the way through - you’ll
» see the mouse again)
» http://www.ascb.org/ibioseminars/includes/player.cfm?name=fuchs&num=2

rev is right. Btw, I did post a lot about Wnt few months ago. According to Fuchs, as you increase Wnt signaling the number of hair growth increases and after a lot of hair growth you get hair tumors(non-cancerous). So they are not random, you’ll see good regrowth before you risk getting tumors. I’d be willing to start with low doses of a compound(preferably topical) that upregulates Wnt and based on the results increase/decrease the usage.

The important issue at this point is to find the right compound that would be safe(health wise) and also is guaranteed to upregulate Wnt signalling. There is no evidence whatsoever that topical lithium chloride(mixed in DMSO) works at all, and that could be a big factor with current experiments not working.


#5

I have been doing many follica experiments without growing any hairs at all.
In the beginning of december I decided to do one last try by first removing the hair from its roots (about 2 cm of the hairline) and wounding 3 days later. According to the patent this alone will increase the number of hair follicles by 100%, in mice that is.
Almost 2 months later I can say that I have grown at least some vellus hair, even beneath my existing hairline. Nothing spectacular or even visible from a distance, but they are there. Unfortunately they dont seem to become any larger, but this is the first time I have seen any result at all. The only topicals I used were minox, flut and elidel, applied from day six. I have used all of these in the prior attempts as well so the result come from the waxing.

I believe that Wnt signaling is the key to make a good number of hair follicles but these will most likely be vellus. The EGFR inhibitor creates bigger hair follicles according to the patent and is most likely what is needed for the follicles to become terminal. EGFR alone will not do the trick and that is why no one has had any provable succes.

So I would like to see someone with access to gefitinib try waxing, wounding (complete removal of epidermis!) and egfr inhibitor. That could very likely result in good, terminal hairgrowth even in bald areas.


#6

I would guess that Caregen’s CG-Keramin2 offers the best publicly (almost) available way to upregulate WNT. I’m sure there are other ways which are much better in theory, but at least Caregen have a product. Unfortunately, I can’t find CG-Keramin2 on their website anymore.

CG-Keramin2 is a DKK1 inhibitor. The dickkopf protein in question is a WNT inhibitor. It is theorized that inhibiting DKK1 would lead to higher levels of WNT. Caregen made a special solution containing DKK1, Noggin and Prohairin (if I’m not mistaken) for a guy on regrowth.com. Baccy and some other people got hold of some of it, I think.

Anyway, it is possible that CG-Keramin2 is included in one of their available kits.


#7

I already DID try waxing, wounding, and using and EGF-R inhibitor.

I used leflunomide pills, which is mentioned in the same sentences as Genfilitib in the patents. It does the same job, it’s just less precise of a method from day to day.

(Remember that the cancer patient with the spectacular regrowth didn’t perfectly stick to any particular set of days on & off ANYTHING, he just took Genfilitb for months. So I don’t think it would have been a deal-breaker if the stuff was in my system a little longer than the ideal.)

It didn’t grow anything substantial. There’s been a little bit improvement after this procedure, but I don’t think the change rates beyond the effects of the dermabrasion alone.

It’s the immune system. It’s gotta be the primary missing factor.

We’ve had plenty of guys with immune system damage that must’ve had some kind of scalp injury over the centuries. If this worked, we’d know about it a long time ago.

And we’ve had plenty of people taking EGF-R inhibiting drugs over the years too. (They put patients on Leflunomide for YEARS at a time.) I don’t believe nobody has ever gotten a bad sunburn or wounded scalp while on the stuff.

So here’s the pattern I see:

Immune system suppression alone = nothing.
Genfilitib alone = nothing.
Immune + genfilitib = new hair.


#8

» I already DID try waxing, wounding, and using and EGF-R inhibitor.
»
»
» I used leflunomide pills, which is mentioned in the same sentences as
» Genfilitib in the patents. It does the same job, it’s just less precise of
» a method from day to day.
»
» (Remember that the cancer patient with the spectacular regrowth didn’t
» perfectly stick to any particular set of days on & off ANYTHING, he just
» took Genfilitb for months. So I don’t think it would have been a
» deal-breaker if the stuff was in my system a little longer than the
» ideal.)
»
»
» It didn’t grow anything substantial. There’s been a little bit
» improvement after this procedure, but I don’t think the change rates beyond
» the effects of the dermabrasion alone.
»
»
»
»
»
»
» It’s the immune system. It’s gotta be the primary missing factor.
»
» We’ve had plenty of guys with immune system damage that must’ve had some
» kind of scalp injury over the centuries. If this worked, we’d know about
» it a long time ago.
»
» And we’ve had plenty of people taking EGF-R inhibiting drugs over the
» years too. (They put patients on Leflunomide for YEARS at a time.) I
» don’t believe nobody has ever gotten a bad sunburn or wounded scalp while
» on the stuff.
»
»
»
» So here’s the pattern I see:
»
» Immune system suppression alone = nothing.
» Genfilitib alone = nothing.
» Immune + genfilitib = new hair.

I dont think immunos will do that much different, I dont think it is the key. Most of the mice in the patent grew hair without beeing immuno suppresed and I used topical immuno (elidel) with topical leflunomide without any result. But we should find out soon with benjis experiment (where did he go by the way?)


#9

"We applied topical LiCl (20 mM) to murine wounds until wound closure (14 days) and harvested the wounds on day 28 for histology…

…Five out of the 6 mice showed histologic evidence of epithelial appendage formation in their wounds on day 28. As seen in figure 3b, the simple stratified epithelium that typically forms over the wound displayed numerous inclusion cyst-like structures superficially within the epidermis and occasionally, formation of primitive hair follicle structures and sebaceous glands"

The wounds they induced were deep, down to and including the upper layer of muscle on the backs of the mice. Possibly too deep, and this could be the reason behind the superficial results. Either way it proves that topically applied Lithium Chloride will upregulate wnt signalling and create hair follicles.

I see no reason why DMSO should deleteriously effect LiCl or change its molecular composition.

From my own experiments I have noticed absorption into the skin is most effective at 70-85% although 90% is supposedly ideal. I also tried at 45% concentration and absorption was minimal, it has also been suggested that at this level absorption would be practically nil.

I didn’t know EGFR inhibition increased EDIHN over Wnt signalling in the follica experiments, could someone point me to a source.

The same goes with immunosuppression.

I think the failure of our experiments is more down to issues regarding wound depth, amount of LiCl or EGFR-I, the combining of LiCl and EGFR-I in a single procedure, and method and concentrations of carrying agents relative to their ability to permeate the skin (emu oil, DMSO, alcohol). So far the experiments most people have conducted seem erratic in that they change a multitude variables after one unsuccesfull result which isn’t particularly helpful.


#10

Most of the mice in the patent grew hair without beeing immuno suppresed andI used topical immuno (elidel) with topical leflunomide without any result.

I don’t think topical leflunomide is a good bet for topical usage though. It has to be metabolized by the body first, and there’s no reason to think that skin entrance will do that.

As for the mice, I have limited faith in any mouse-based knowledge. It seems pretty hard NOT to grow hair on mice.

But any time they had a human skin graft being used on their backs, they automatically would’ve had to be immune suppressed just to stop that from being an unwanted variable in the experiment.

I also suspect that the immune suppression probably has to be MAJOR for humans like us to get this to work. Quite possibly at organ transplant patient levels.

There are plenty of cancer & RA patients who’ve spent time on EGF-R inhibitors. And I’ll bet there are TONS of them with what you could call at least “compromised” or “weakened” immune systems, for one reason or another. But most of these people still aren’t regrowing hair as soon as they scuff their head on something. That makes me think the immune thing must be MAJOR.

I don’t have a great idea for experimenting with immune suppression like that.

The only safety step I can think of would be to use a combination. I’m thinking that some moderate systemic (oral) suppression + a decent topical = more serious suppression just at the site of the topical.


#11

Albert Kligman told Cotsarialis (Cotsarialis in an interview) that he noted some de noveau hair follicle formation in ance scar dermabrasion patients.
Hydrocortisone creams (now availaible in drug stores) were probably all that were given to those patients, possibly with some lidocaine ointments for pain, etc.

Corticosteroids are indeed mentioned in that patent. One wonders if a getfitinib tablet could simply be crushed up and placed in some hydrocortisone cream for a night and administered to a abraded or TCA-peeled area. The patent certainly seems to indicate the process will be with a topical. Hydrocortisone should have been the corticosteroid available in the seventies if memory serves. I think the rest of them have only been synthesized since then. They suppress immuno response.

My experiment for Z79, with nine days of 100 mgs of cyclo and about 7 days of getfitinib, yileded absolutely nothing that I could see. I didn’t wash the hair and all that jazz either. Like Cal, I think the immunosuppression might have to be rather high in the area in question to keep any inflammation from impedeing the process. In neo-natal mice, inflammation keeps hair from forming period when its artifically induced.

Even if one got hair, would it be permanent? This is a bigger problem to me. Im hoping that this can be done to donor-areas so someone can simply keep making “more” donor-quality-hair (Hair-multiplication).


#12

For any of you experimenting with this at home, Ive an idea.

One could wound (TCA peel, abrade, etc.) about two to three nickel-sized areas along the NAPE OF THEIR NECK right before their hairline starts. In fact one could do a couple of these directly under the back hairline and a couple on each side behind the ears on the neck.

One could immediately start applying cortisone creams ( immunosuppressive and at your drug store gents) to a couple of the wounds, and then wait 5-6 days to apply it with the other wounds. One could use a egf-inhibitor with some etc. If you made six little wounds, you could try six different “mixes” and apply the topicals at different times accounting for post-reepilithialization, etc. This way you could wash the front and top and sides of your head and not effect your life in any way-----you could go about your business as normal with no need to “stop” your life for a couple of weeks. Your existing hair should cover the peeled or abraded areas up anyway. No one would notice.

Wounding the frontal hairline and all of that jazz (especially if you dont wash the abraded area in fear that some detergents in shampoo might nix the cellular processes attempting to take place) make experimenting like this a “life-interrupter”. By wouding the back of the neck just under the hairline any anti-androgens you may be one (finas, dutas, saw palmetto, etc.) shouldn’t suppress any de noveau growth or keep it “small”, but still not interrupt your life.

If one was not on any anti-androgen internally (using topical anti-androgens like fluridil, spiro, etc.) then a guy could just wound a un-hairy spot on his chest or two and see if he could get some growth there that wasn’t there before. Any growth that occured doing this should “stand out” for pictures later also.

This is just my opinion for those experimenting for a way to tinker with this without causing themselves signifigant personal downtime and a way to not actually damage the scalp by over-wounding it by trying it over and over again. I dont think abrading your scalp or TCA peeling it is something that should be done every couple of months guys. You might damage it unceccessarily and screw the pigmentation up “up there” where the whole world will be seeing it.

Just an idea.


#13

» Albert Kligman told Cotsarialis (Cotsarialis in an interview) that he noted
» some de noveau hair follicle formation in ance scar dermabrasion patients.
»
» Hydrocortisone creams (now availaible in drug stores) were probably all
» that were given to those patients, possibly with some lidocaine ointments
» for pain, etc.
»
»
» Corticosteroids are indeed mentioned in that patent. One wonders if a
» getfitinib tablet could simply be crushed up and placed in some
» hydrocortisone cream for a night and administered to a abraded or
» TCA-peeled area. The patent certainly seems to indicate the process will be
» with a topical. Hydrocortisone should have been the corticosteroid
» available in the seventies if memory serves. I think the rest of them have
» only been synthesized since then. They suppress immuno response.
»
»
»
» My experiment for Z79, with nine days of 100 mgs of cyclo and about 7 days
» of getfitinib, yileded absolutely nothing that I could see. I didn’t wash
» the hair and all that jazz either. Like Cal, I think the immunosuppression
» might have to be rather high in the area in question to keep any
» inflammation from impedeing the process. In neo-natal mice, inflammation
» keeps hair from forming period when its artifically induced.
»
»
»
» Even if one got hair, would it be permanent? This is a bigger problem to
» me. Im hoping that this can be done to donor-areas so someone can simply
» keep making “more” donor-quality-hair (Hair-multiplication).

I assume it was 7 days of oral getfitnib


#14

yes, it was oral.

The cyclo and the getfitinib were oral. I didn’t want to risk anything. I got literally nothing from it. To be fair, I only had 9 days worth of cyclo and not enough of it at that.

Hitting the window right after re-epilithialization and continuing to have the conditions “just right” for the seven-day “hair making process”*** are going to be obstacles follica will have to overcome.

****seven day hair making process- When wnt was inhibited from day 11-14 or 14-17 in mice, only 3 and 2 hairs formed vs. 96 hairs for mice when wnt was inhibited on days 1-10 post wounding. Humans can re-epilithialize by day 6 or 7 at the earliest, but can take longer. Hitting the window, and not mucking up the experiment from the day the window starts till it ends will obviously be crucial. When wnt is inhibited in mice from day 1-10, the hairs are pigmented, when its not, they are white. So really…what happens from the day you wound until the day hairs are completely formed is pretty important. That could be a 17 day process or even a bit longer depending on wound depth.


#15

» yes, it was oral.
»
»

From the 2008 patent:

In one aspect, the invention features a composition including from 0.001% to 0.1% (w/v) of a small molecule EGFR inhibitor formulated for topical administration, wherein the EGFR inhibitor is a non-naturally occurring nitrogen-including heterocycle of less than about 2,000 daltons, or a metabolite thereof. hi another aspect, the invention features a kit including (i) a composition including from 0.000001% to 10% (w/v) of a small molecule EGFR inhibitor formulated for topical administration, wherein the EGFR inhibitor is a non- naturally occurring nitrogen-including heterocycle of less than about 2,000 daltons, or a metabolite thereof, and (ii) instructions for applying this

The patent constantly refers to topical administration of all the compounds.
It does, however, mention oral as a possible means of delivery but as I recall, it only mentions it once.
I suspect the molecule size of gefitinib is the reason it was chosen for transdermal delivery.


#16

It looks like the discussion is back to gefitinib. Why aren’t you guys concentrating on Wnt? I know EGFR will multiple the hair growth potential, but as it is most of the people aren’t getting any decent hair regrowth to begin with - forget multiplying the potential. If we can just get the timming of Wnt right and get at least few terminal hairs to grow that would definitely be a big step forward.


#17

» It looks like the discussion is back to gefitinib. Why aren’t you guys
» concentrating on Wnt? I know EGFR will multiple the hair growth potential,
» but as it is most of the people aren’t getting any decent hair regrowth to
» begin with - forget multiplying the potential. If we can just get the
» timming of Wnt right and get at least few terminal hairs to grow that would
» definitely be a big step forward.

It seems the only guys who are getting growth are wounding deeply and over a large area. THAT’S the starting point. Wounding (if done correctly) should be enough to get SOME results.
As for wnt, in my attempts I’ve always tried to inhibit EGF AND upregulate wnt.


#18

» It looks like the discussion is back to gefitinib. Why aren’t you guys
» concentrating on Wnt? I know EGFR will multiple the hair growth potential,
» but as it is most of the people aren’t getting any decent hair regrowth to
» begin with - forget multiplying the potential. If we can just get the
» timming of Wnt right and get at least few terminal hairs to grow that would
» definitely be a big step forward.

Im with you on this one. I believed EGFR inhibitor would do the trick, but we have tried so many combinations with it. If it was the key to hair growth we would have gotten some good regrowth by now regardless of other drugs used at the same time.
Every time Cotsarelis talks about this, including the nature article, he states that upregulating Wnt grows a lot of hair. EGFR inhibitors does not seem to do this. So what does upregulate Wnt, besides lithium, wich does not seem to be efficiant enough?


#19

» » It looks like the discussion is back to gefitinib. Why aren’t you guys
» » concentrating on Wnt? I know EGFR will multiple the hair growth
» potential,
» » but as it is most of the people aren’t getting any decent hair regrowth
» to
» » begin with - forget multiplying the potential. If we can just get the
» » timming of Wnt right and get at least few terminal hairs to grow that
» would
» » definitely be a big step forward.
»
» Im with you on this one. I believed EGFR inhibitor would do the trick, but
» we have tried so many combinations with it. If it was the key to hair
» growth we would have gotten some good regrowth by now regardless of other
» drugs used at the same time.
» Every time Cotsarelis talks about this, including the nature article, he
» states that upregulating Wnt grows a lot of hair. EGFR inhibitors does not
» seem to do this. So what does upregulate Wnt, besides lithium, wich does
» not seem to be efficiant enough?

guys… I’m kinda new to this forum and i’m having some difficulty in catching up on all the readnig i’ve missed… this is obviously a follow up report for something that was started some while ago… i read most the “scalp wounding and eventual results” thread… but that too seems a bit random. Am I missing the starting thread here? I’d be greatly interested in reading the paper and about the patent from proceedings which you guys have derived the wounding methods… wld be greatful if someone could point out what i’m missing here… thanks


#20

http://www.stanford.edu/~rnusse/assays/actvwnt.html

LiCl would seem to be the only method available to us out of all those mentioned. You can use it like salt and take a pinch of it orally. It used to be used as a table-salt replacement. It gets hot in the mouth though and has to be washed down pretty quickly. It has --LONG TERM-- toxicity, so its not something to do for several months.

Wnt was INHIBITED from day 1 to day 10 in mice to produce PIGMENTED hairs, but mice re-epilithialize more slowly than people do. People might re-epilithialize as early as day 5 or 6 or as late as day 13 or 14. Its different based on wound depth and personal dermal characteristics.

These variables are the reason I think it would be wise for men to just to do small spots at the nape of the neck or the chest (nickel or quarter sized) and try various approaches to get one “that works”. One would not have to interrupt their lives to try a few small experiments in this way.

Corticosteroids (hydrocortisone) and egf-inhibitors and wnt mimetics are mentioned in the first patent, and the corticosteroids and egf-inhibitors are also mentioned in the second patent.

"Anti-inflammatory agents In certain embodiments, an antiinflammtory agent can be used in the compositions, methods, and kits of the invention. Useful antiinflammtory agents include, without limitation, Non- Steroidal Anti-Inflammtory Drugs (NSAIDs) (e.g., naproxen sodium, diclofenac sodium, diclofenac potassium, aspirin, sulindac, diflunisal, piroxicam, indomethacin, ibuprofen, nabumetone, choline magnesium trisalicylate, sodium salicylate, salicylsalicylic acid (salsalate), fenoprofen, flurbiprofen, ketoprofen, meclofenamate sodium, meloxicam, oxaprozin, sulindac, and tolmetin), COX-2 inhibitors (e.g., rofecoxib, celecoxib, valdecoxib, and lumiracoxib), and corticosteroids (e.g., alclometasone dipropionate, amcinonide, betamethasone dipropionate,

betamethasone valerate, clobetasol propionate, desonide, desoximetasone, dexamethasone, diflorasone diacetate, flucinolone acetonide, flumethasone, fluocinonide, flurandrenolide, halcinonide, halobetasol propionate, hydrocortisone butyrate, hydrocortisone valerate, methylprednisolone, mometasone fiiroate, prednisolone, or triamcinolone acetonide)."