71 replies to this topic

[bernard]

OC000459 is not really a PGD2 inhibitor though. It's more of a receptor modulator/blocker.

[niner]

Tatsumaru, thanks for all this great information. I have to retract what I said about the current crop of drugs, after reading Garza and the huge CRTH2 thread at HLH. Now I want to see some people getting results. I guess it's too soon- maybe in a few months?

[Logic]

Check the study that I posted. Apparently MPB has a lot more to do with Prostaglandin D2 than with DHT.

Drugs known as Mast Cell Stabilizers used for certain allergies do inhibit PGD2 and might result in dramatic hair growth.

Ketotifen is one such Mast Cell Stabilizer. Anyone know if it's safe for longer term use ?

PGD2:

http://en.wikipedia....rostaglandin_D2
"...research found PGD2 prevents hair growth, and mice that were genetically inclined to produce higher levels of PGD2 had inhibited hair growth. The research also found PGD2 levels were much higher in balding scalp tissue than nonbalding scalp tissue. The paper suggested one of the receptors involved in production of PGD2, GPR44, would therefore be a therapeutic targets for androgenic alopecia in both men and women with hair loss and thinning..."

http://www.ncbi.nlm....pubmed/18223672
"...aspirin reduced only PGD2 by 86%..."

Thus I take 81mg enteric coated asperin with Vit C as well as have asperin in my shampoo. FWIW

Circumin also blocks PGD2 and is part of my stack for all sorts of reasons.

[xztop123]

Aspirin surely cannot be the only effective one. I'll have to spend a few hours and get to the bottom of it. Aspirin applied topically with DMSO as a carrier? I dont want to pop aspirin every day

[nowayout]

Circumin also blocks PGD2 and is part of my stack for all sorts of reasons.

Be careful. It is estrogenic, and actually causes sexual problems in some men.

[bernard]

I wouldn't mind a little uptick on the estrogen side. After all estrogen has multiple benefits incl. cognitive, joints, immune system, hair, nails, libido etc.
In fact high estrogen levels are most likely beneficial. Even though you might think gynecomastia is caused by high estrogen levels, recent studies show that it's the DHT:fTestosterone:Estrogen ratio that plays the most important role in gynecomastia. As long as your ratio is ok maybe higher estrogen levels are only beneficial in terms of hair etc.

[nowayout]

Like almost everything the benefits of estrogen form an inverted U-curve, so it incorrect to say that if some is good, more is better.

[bernard]

Yes, I agree. No hormone or substance is universally good, at least not to my knowledge. Maybe there is a cure-it-all somewhere out there.

[Picard]

The following study investigates the involvement of a gene in hair loss:

http://www.nature.co...l/5700999a.html

"Here, we screened dihydrotestosterone (DHT)-regulated genes in balding DP cells and found that dickkopf 1 (DKK-1) is one of the most upregulated genes. DKK-1 messenger RNA is upregulated in 3–6 hours after 50–100 DHT treatment and ELISA showed that DKK-1 is secreted from DP cells in response to DHT. A co-culture system using outer root sheath (ORS) keratinocytes and DP cells showed that DHT inhibits the growth of ORS cells, and neutralizing antibody against DKK-1 significantly reversed the growth inhibition of ORS cells."

This follow-up, animal-based study analyzes the mechanisms by which this may occur:

http://www.nature.co...jid201224a.html

"Herein, we report that recombinant human DKK-1 (rhDKK-1) injection into the hypodermis of mice during anagen caused premature onset of catagen, whereas neutralizing DKK-1 antibody delayed anagen-to-catagen transition in mice. Moreover, treatment with rhDKK-1 led to a decrease in final hair follicle length, whereas DKK-1 antibody led to an increase compared with control animals."

So, what can be done with this information? Intuitive research approaches might include disabling the upstream process by operating on DHT or targeting the downstream effects by regulating expression of this gene. Everyone is familiar with the former, but here's a study showing promise on the latter:

http://www.bmbreport...TEzMiUyOS5wZGY=

"We also found that DHT-induced activation of DKK-1 promoter activity was significantly repressed by L-threonate. Moreover, a co-culture system featuring outer root sheath (ORS) keratinocytes and DPCs showed that DHT inhibited the growth of ORS cells, which was then significantly reversed by L-threonate. Collectively, these results indicate that L-threonate inhibited DKK-1 expression in DPCs and therefore is a good treatment for the prevention of androgen-driven balding."

Here's one lab's whitepaper on the compound:
http://www.merckmill...yMAAAEWzdUfVhTl

"A 2-aminopyrimidine compound that counteracts the antagonizing effect of Dkk-1 (Dickkopf-1) against Wnt-3a/LRP5 interaction and prevents Dkk-1-mediated Kr2/LRP5/Dkk-1 complex formation and internalization. Shown to successfully rescue cellular response to Wnt-3a stimulation in the presence of Dkk-1 (EC = 0.63 µM in a cell-based TCF-luciferase assay) and double the tibia trabecular bone 50 in vitro formation in OVX rats in a period of 28 days via an oral dose of 10 mg/kg/day in vivo."

[bernard]

Very interesting. I'll try to get some L-Threonate. Never heard of it before though, only L-Threonine. I wonder if they are the same or correlated, but that's something I can find on my own.

[Picard]

Please do let me know the outcome of your search. I'm also interested, but have only found elemental salts (like magnesium and calcium).

[niner]

Very interesting. I'll try to get some L-Threonate. Never heard of it before though, only L-Threonine. I wonder if they are the same or correlated, but that's something I can find on my own.

They're different. Threonate is the ionized form of threonic acid, and is related to ascorbic acid. Magnesium Threonate created a big buzz a while back. In a quick look, I didn't find any sodium or potassium threonate on the web, but you can buy magnesium threonate.

[effem]

L-Threonate...

http://www.thekanesh...eonate-10g.html

[JBForrester]

Well I'm a girl and 3 years ago had went to a hair transplant center for a patch of hair that was missing from an accident when I was 14. The Dr., who used to be a general pract., told me to use the following and it seemed to ameliorate the problem a bit. I have NO (or limited) scientific proof that this works though, so I'd suggest you do your own research:

- Saw Palmetto 160mg daily
- Glucosamine HCL 500mg/Chondroitin Sulfate 400mg 3/day
- L-Lysine 500mg daily
- Multi-vitamin 1/day
- Vitamin E 200 i.u. 1/day
- MSM 1500 1/daily
- Ester-C 1000mg 2/day
- Mediterranean Diet
- Nitrate- and Sulphate-free everything (foods, products, etc)

And... can't remember the rest. Sorry. I can't post links right now because I'm new (one more post and I'm in!) but supposedly Saw Palmetto lowers DHT levels:

Talpur, Nadeem, et al. "Comparison of Saw Palmetto (extract and whole berry) and Cernitin on prostate growth in rats." Molecular and cellular biochemistry 250.1 (2003): 21-26.

[Picard]

L-Threonate...

http://www.thekanesh...eonate-10g.html

I'm pretty interested in this, but was taken aback by the $50 shipping. I'd consider it if I could split the order with someone.

[bernard]

The Kane Shop are yet to build up a reputation for themselves. They are selling one of the most promising compounds - CRTH2 antagonist, which is purportedly able to turn this:



into this:



with the help of valproate and ciclopirox.
And since CRTH2 antagonists are extremely hard to obtain since they are most novel I'd be doubting whether it's a true product or a fake.

[Picard]

The pessimism is often warranted with operations like these. Unfortunately, you don't have many better options when following the cutting edge.

If I recall correctly, this particular supplier has survived scrutiny in the past through independent testing. I assume we're members of the same HL communities, however, and think it wise to contact GansterBoy with any reservations.

[bernard]

Ok, so the trick appears to be something that involves a CRTH2 antagonist, anti-androgen and hair follicle growth stimulator. These are some seriously experimental compounds. If anyone could come up with something that even resembles a protocol for use I could synthesize these compounds and try them on myself and report progress. I honestly don't want to wait for another 10 years. These could have some weird side effects but I'm willing to risk it for the sake of hair rejuvenation. Please come up with some information.

CRTH2 Antagonists:

http://www.thekanesh...s/oc000459.html - OC000459
http://www.thekanesh...ethanol-1g.html - OC000459 Ethanol Solution
http://www.thekanesh...089-500-mg.html - TM30089

+

http://www.thekanesh...-valproate.html - Sodium Valproate

[niner]

If anyone could come up with something that even resembles a protocol for use I could synthesize these compounds and try them on myself and report progress.

In the field of chemistry, to synthesize a compound means to create it in the lab. Unless you already have a well-stocked lab, I doubt very much that you could do this for less than it would cost to buy it. As far as a protocol for use, what are people on the hair loss forums saying? If Kane is selling it, someone must be buying...

[bernard]

I do own a lab. I'm not synthesizing for cost's sake though. I don't trust Kane so I want to make my own chems.

[niner]

ok, that changes the picture. Unless it's an easy synthesis, you could just get it from Kane and analyze it in your own lab, if you have the instruments. Of course, if you made some, you could make a big batch and sell some of it. I'm still wondering if anyone has tried this yet and reported results. Are there a bunch of people saying that it worked great for them? Anyone who tried it and said it didn't work?

[Picard]

ok, that changes the picture. Unless it's an easy synthesis, you could just get it from Kane and analyze it in your own lab, if you have the instruments. Of course, if you made some, you could make a big batch and sell some of it. I'm still wondering if anyone has tried this yet and reported results. Are there a bunch of people saying that it worked great for them? Anyone who tried it and said it didn't work?

I've monitored the general response and see that a significant percentage report shed and itching are reduced, if not halted. Other results run the gamut as you'd expect from any possible therapy. Some report fairly impressive regrowth with picture evidence, though these users are often using other treatments in conjunction.

There were solubility issues with the first batch of OC000459, so that likely has cooled some of the interest in it.

[bernard]

ok, that changes the picture. Unless it's an easy synthesis, you could just get it from Kane and analyze it in your own lab, if you have the instruments. Of course, if you made some, you could make a big batch and sell some of it. I'm still wondering if anyone has tried this yet and reported results. Are there a bunch of people saying that it worked great for them? Anyone who tried it and said it didn't work?

I've monitored the general response and see that a significant percentage report shed and itching are reduced, if not halted. Other results run the gamut as you'd expect from any possible therapy. Some report fairly impressive regrowth with picture evidence, though these users are often using other treatments in conjunction.

There were solubility issues with the first batch of OC000459, so that likely has cooled some of the interest in it.

Any idea which of the two wnt stimulators (Valproate and Threonate) produces better effects ?

[Picard]

ok, that changes the picture. Unless it's an easy synthesis, you could just get it from Kane and analyze it in your own lab, if you have the instruments. Of course, if you made some, you could make a big batch and sell some of it. I'm still wondering if anyone has tried this yet and reported results. Are there a bunch of people saying that it worked great for them? Anyone who tried it and said it didn't work?

I've monitored the general response and see that a significant percentage report shed and itching are reduced, if not halted. Other results run the gamut as you'd expect from any possible therapy. Some report fairly impressive regrowth with picture evidence, though these users are often using other treatments in conjunction.

There were solubility issues with the first batch of OC000459, so that likely has cooled some of the interest in it.

Any idea which of the two wnt stimulators (Valproate and Threonate) produces better effects ?

Unfortunately, no. Topical threonate has been tried by very few. I also do not know how stable/effective it could be in an Alcohol/PG solution. However, I've personally mapped out the mechanisms of action related to its effects on DKK and feel its a promising avenue for additional research.

I can recall some users reporting success while on Sodium Valproate, but these users almost invariably attribute their success to some other growth stimulant. I remember some scary-sounding side effects, such as bleeding gums. Further, the possible mechanism seems less convincing than threonate's.

[niner]

Thanks, Picard. So OC000459's a promising treatment, but sounds like it's not a miracle. Do you have any sense of what fraction of people have a good response? Does it do anything at all for long-term hairloss? It's being given to humans systemically at 200mg/day in this clinical trial, so I don't think that we need to be too worried about using it topically. Just from looking at the structure, I'm not surprised that there are solubility problems. Kane claims it goes into an ethanol/water mixture. I doubt that you can get by with much water there. There's always DMSO and the like though. Regarding the bleeding gums from valproate, is that just from topical use? Valproic acid is a pretty common systemic drug.

Edited by niner, 11 February 2013 - 10:56 PM.

[bernard]

Thanks, Picard. So OC000459's a promising treatment, but sounds like it's not a miracle. Do you have any sense of what fraction of people have a good response? Does it do anything at all for long-term hairloss? It's being given to humans systemically at 200mg/day in this clinical trial, so I don't think that we need to be too worried about using it topically. Just from looking at the structure, I'm not surprised that there are solubility problems. Kane claims it goes into an ethanol/water mixture. I doubt that you can get by with much water there. There's always DMSO and the like though. Regarding the bleeding gums from valproate, is that just from topical use? Valproic acid is a pretty common systemic drug.

From what I read OC000459 only halts hair loss but does not promote hair growth per se.

Does Magnesium L-Threonate provide enough Threonate for wnt stimulation ?

Edited by Tatsumaru, 11 February 2013 - 11:06 PM.

[Picard]

This is far from scientific, but my relative sense of OC000459 is that over half report good results in slowing loss. Perhaps 5% report actual regrowth. What may undermine the validity of this impression are the solubility and duration of treatment. I believe it became available on Kane's site in October, which means the most devoted users could be at the ~4 month mark. My understanding is that 6 months should be given to evaluate the efficacy of these treatments. Despite the feedback thus far, many are pushing to use TM30089 due to the better solubility profile.

The valproic acid was used topically.

Tatsumaru, I've wondered the same. We haven't a clue what concentrations might be effective. We have studies showing that DKK-1 neutralization promotes growth and may be achieved with Threonate. Though, those studies don't provide any dosing instructions. The one patent filed for a possible compound includes a very broad concentration range (.5% - 15% if I recall correctly).

Additionally, I'm a little reluctant to play chemist in separating out binders/excipients while guessing at the process's effects on threonate activity.

Edited by Picard, 11 February 2013 - 11:20 PM.

[niner]

Additionally, I'm a little reluctant to play chemist in separating out binders/excipients while guessing at the process's effects on threonate activity.

I wouldn't worry too much. All you need to do is dissolve it in cool water and filter it. A coffee filter would even work. Which threonate salt are you using? Calcium? That's what was used in this paper.

[bernard]

Do you apply the threonate topically as well or it's an oral preparation ?

[mikey]

So here's a new twist. A vitamin D analog that is reported to grow hair back.
http://saypeople.com.../#axzz2SRgJZsMR

Here's the case report - http://www.ncbi.nlm....f/ad-24-341.pdf

A doctor can prescribe it as a prescription called Daivonex, 50 ug/mL (calcipotriol).

There are numerous sources of another version on the net, sold as non-prescription Dovonex, such ashttps://www.northwes...ovonex ointment which is not just calcipotriol - also containing calcipotriene. I don't know what differences might there be.

Maybe one of the chemists here can chime in and provide details.

Michael