Newly Discovered Factor in Androgenetic Alopecia. The Cure is Near?

[waynakyo]

Re: A recently discovered new factor in AA, the cure is near

Havent posted in a long time as i generally havent focussed much on hairloss and related issues in a few years. Was very interested to do a pubmed search to see if anything new had happened research wise and to see that this result had finally been published and has caused a big ruckus.

welcome back.. hope you'll keep visiting.. your opinions are much appreciated here. No one mentionned the fact that this was discussed 4 years ago. It seems to me this makes it less of an astonishing finding as it is currently portrayed..I would guess ... why they have waited for so long...

Anyway -- if you come out with any brilliant ideas of products that we can use that target one of the 3 channels, grateful if you can share.

 

[mlb]

Re: A recently discovered new factor in AA, the cure is near

Here is what I dont understand it says in the same article that Merck while testing a drug that does this sees no results for hair. So I mean if a drug they have in advanced testing doing this already shows no hair results what do we make of that?

-------------------------
Merck isn’t studying the anti-flushing drug in hair loss, said Ian McConnell, a Merck spokesman, in a telephone interview. “We haven’t seen any signalsâ€￾ in patient trials that the therapy might reduce baldness, he said.

Laropiprant (Merck's drug) selectively blocks the PD1 receptor - , that isn't the receptor that Cotsarelis was talking about. So Merck's drug won't be of any use to us. I posted a quote on page one of this thread from another forum explaining that.

It is also possible that an oral medicine does not provide an adequate dose to the follicle.

Ramatroban is a weaker CRTH2 inhibitor than Setipiprant but it is an inhibitor nonetheless. It has been prescribed for allergies in Japan for years. If it worked for hair orally i'm sure that would have been discovered by now. But topically perhaps?

 

[odalbak]

Re: A recently discovered new factor in AA, the cure is near

Personnally I'm only interested in topical solutions. Long term use of drugs with systemic effects is a no no with me. But others will differ.

 

[waynakyo]

Re: A recently discovered new factor in AA, the cure is near

link to paper:

http://www.hopkinsmedicine.org/dermatol ... _Garza.pdf

the biologists here need to help us figure out what is really a good inhibitor of PGD2... I heard Quercetin is one.

 

[waynakyo]

Re: A recently discovered new factor in AA, the cure is near

http://www.mastcellmaster.com/documents ... h-IJIP.pdf

http://www.biomedcentral.com/content/pd ... 0-4-47.pdf

 

[odalbak]

Re: A recently discovered new factor in AA, the cure is near

Thanks waynakyo.

SCG is PGD2 inhibitor.

"Sodium cromoglicate (SCG), a chromone developed in the 1960’s as an inhaled powder for the treatment of asthma has subsequently been used for the treatment of allergic rhinitis, allergic conjunctivitis, food allergy and systemic mastocytosis. A number of studies have investigated the effect of topically applied SCG in atopic dermatitis. Although variable effects have been reported, probably because of the hydrophilic nature of SCG that limits its penetration in intact skin, several have found a significant reduction of itch."

"SCG was introduced into the skin of healthy volunteers both by iontophoresis and by topical application using a new 4% cutaneous emulsion (Altoderm™). The skin was then challenged with intradermal histamine. (…) Topically applied SCG, administered in a new cutaneous emulsion base, significantly reduced the itch and flare caused by intradermal histamine. The effect was greatest in atopic subjects and increased with the concentration of SCG in the emulsion. (…) There were no effects on wheal or blood flux."

"SCG has no anti-histaminic activity"

 

[TravisB]

Re: A recently discovered new factor in AA, the cure is near

Don't you think that if it really helped with baldness thay would notice it by now?

 

[odalbak]

Re: A recently discovered new factor in AA, the cure is near

You mean SCG? It's never been used on balding scalp over a period of several months as far as I know.

People have been using aspirin since 1853… We should know all its effects by now, right? http://www.bbc.co.uk/news/health-11930988

 

[squeegee]

Re: A recently discovered new factor in AA, the cure is near

Hey all,

Havent posted in a long time as i generally havent focussed much on hairloss and related issues in a few years. Was very interested to do a pubmed search to see if anything new had happened research wise and to see that this result had finally been published and has caused a big ruckus. To give some perspective this was something some people were talking about here over 4 years ago thanks to the miracle of online patents:

viewtopic.php?f=32&t=43715&p=412209&hilit=+pgd2#p412209

Its funny because around the same time Cotsarelis filed the patent on that whole wnt wounding thing that became the basis of Follica and that kind of swept this PGD2 thing aside. The PGD2 synthase elevation always seemed very dramatic and very well demonstrated in the info we had from the patent but as time went by and the results were never published it sort of became a secondary thing - it was only one set of unpublished findings from one group after all, who seemed set on pursuing a treatment based on other findings commercially. Still there were other hints that it might be really important such as hte effect of PGF2 analogs like latanorast on hair growth and the fact that mice which overexpressed COX-2 in skin developed hair miniaturization (an important point because hair miniaturization, not just hair loss, is a defining characteristic of male pattern baldness) and enlarged sebaceous glands.
http://www.pnas.org/content/98/13/7629.figures-only

Anyway some thoughts:
Basically:
Arachidonic Acid -- COX1/COX2--> Prostaglandin H2 --PG D Synthase --> PGD2 <binds to> PGD2 receptor
In this case the PGD synthase is apparently the PTGDS "lipocalin type" that is commonly found in the brain and not the PGDS type associated with mast cells. IN male pattern baldness it seems that something downstream of androgens upregulates this PTGDS and thats why we are getting so much PGD2 unlike in the mice where it was COX2 being upregulated and a whole host of prostaglandins being overexpressed. As mentioned the PGD2 receptor involved here is CTRH2.

So it seems we have 3 targets:
1) COX1/COX2 - lower all prostaglandin production
2) PTGDS - lower PGD2 production
3) CTRH2 - stop PGD2 from binding.

In terms of 2) and 3) I'm not sure that there is a lot we can do by ourselves. Indomethicain is a weak antagonist of CTRH2. Selenium Chloride (SeCl4) and sodium selenite (Na2SeO3) are inhibitors of PTGDS but from what i gather you wouldnt want to mess with selenium chloride at least. OTOH of course the commonly available NSAIDs like aspirin/ibuprofen/paracetemol are COX1/2 inhibitors. Still i havent come up with much research in terms of how to effectively apply them topically and how effective they might be.Theres also a bit about flavonoids like luteolin and quercetin interfering with PGD2 production but its not clear on the pathways involved (it may be more relevant to the PGDS pathway) but some of it at least appears to be COX related.

Happy to see you back harold! Always enjoy reading your posts. unk:

 

[Loomis]

Re: A recently discovered new factor in AA, the cure is near

Here is what I dont understand it says in the same article that Merck while testing a drug that does this sees no results for hair. So I mean if a drug they have in advanced testing doing this already shows no hair results what do we make of that?

-------------------------
Merck isn’t studying the anti-flushing drug in hair loss, said Ian McConnell, a Merck spokesman, in a telephone interview. “We haven’t seen any signalsâ€￾ in patient trials that the therapy might reduce baldness, he said.

Laropiprant (Merck's drug) selectively blocks the PD1 receptor - , that isn't the receptor that Cotsarelis was talking about. So Merck's drug won't be of any use to us. I posted a quote on page one of this thread from another forum explaining that.

It is also possible that an oral medicine does not provide an adequate dose to the follicle.

Ramatroban is a weaker CRTH2 inhibitor than Setipiprant but it is an inhibitor nonetheless. It has been prescribed for allergies in Japan for years. If it worked for hair orally i'm sure that would have been discovered by now. But topically perhaps?

You wouldn't use it orally though, it would be reformulated into a topical, that's what Cotsarelis was talking about when he mentioned drugs being in trials that could target the receptor.

 

[waynakyo]

Re: A recently discovered new factor in AA, the cure is near

so any ideas of how to get hold of SCG or Ramatroban ? or you guys waiting to hear the results of the trials in 5 years time ?

if it wasn't for experimental drugs I would have shaved my head be now.

 

[odalbak]

Re: A recently discovered new factor in AA, the cure is near

I realized I had at home a small bottle of eye drops against eye inflammation from hayfever, it contains 2% of SCG. 2 grams overall. It may not be enough for this special use but I always could try apply this on my scalp and see. The normal daily posology is 1 drop in each eye up to 6 times a day for 3 months. If 12 drops every day in the eyes is okay, it should be safe on the scalp I guess. There are no side effects observed when applied in the eyes.

 

[bornthisway]

Re: A recently discovered new factor in AA, the cure is near

Someone else tried topical quercetin in 2004 and claimed improvement. Quoted below from another forum.

"Tried absolutely everything to halt hairloss with more or less luck, I reached the NW2 Mark due probably to the use of Innovate.

I would say that minoxidil and finasteride were my best friend for the last 4 years, hairs are cycling very rapidely so I shed a lot (100+ hairs a day) but recover rapidely.

I droped innovate after eight months of use (a hair destroyer !!).

My current regimen is :

External : classic OzBrew (2x a day) (7 months + on it) + T-Flavanone (7 months + on it)

Internal : Hair vitamins + finasteride 2mg + 2g Quercetin + 2g MSM

And I'm pleased with the results since I removed innovate !!

I'm interessed by the AR blocker : Fluridil that I'll add next week to my regimen at night to help totally recover my temples.

So there is an important information for you guys : I tried topical quercetin during 2 months, and I was pleased with results (Mix my own DMSO + Distilled Water + 2g Quercetin topical) but I had to stop.

It seemed to help a lot with the shed and thickening. For me the effects of a topicals quercetin are similars to topical spironolactone or fluridil in a muchhhhhh cheaper way (60 ml of this mix costs nothing).

The only problem (great one) : IT STAINS A LOT !!! An horrible yellow that goes everywhere, turns to red when in contact with sponges, a total nightmare, to make it go away from your skin is a real problem too, my bathroom is totally yellow after 2 months of use.

So topical quercetin is good for your hair ? : YES, I'm pretty sure of that (for me internal quercetin has no effect at all, I don't know why i'm always using it ...), one month after adding topical quercetin shed decreased a lot !!!!

If you have a wife would you be able to keep her if you use it ? : NO, mine asked me to choose between the yellow stuff and her lol

Hope this help.

Gilles "

I forgot if we can link to other hair loss sites but should be easy to find.

 

[odalbak]

Re: A recently discovered new factor in AA, the cure is near

The question is does Quercetin inhibit PGD2 only?

"Researchers found that as PGD2 inhibits hair growth, other prostaglandins work in opposition, enhancing and regulating the speed of hair growth."

 

[waynakyo]

Re: A recently discovered new factor in AA, the cure is near

Bornthisway, thanks for the interesting story.. I am going to try this but have to find a drug that I can get and that is known to inhibit PGD2 well... these stuff they put in their eyes 4 times a day i am sure I can do the same on my scalp.


also found this:
http://circres.ahajournals.org/content/82/2/204.full

 

[waynakyo]

Re: A recently discovered new factor in AA, the cure is near

http://www.arraybiopharma.com/_document ... ent342.pdf

 

[bornthisway]

Re: A recently discovered new factor in AA, the cure is near

The question is does Quercetin inhibit PGD2 only?

"Researchers found that as PGD2 inhibits hair growth, other prostaglandins work in opposition, enhancing and regulating the speed of hair growth."

Well, if someone had an overly positive effect on his hair I would think it's less likely that it would adversely affect hair growth. It may not have an effect (if any) on other prostaglandins to the extent that it would be detrimental. Luteolin should have a positive effect as well but I didn't find any topical experiences for hair loss. They both would likely have yellow staining which is something I could live with if effective.

There's other options people are talking about as well (which I haven't read up on), I guess we'll just have to wait and see. Quercetin is at least super cheap, safe, and it's been tried out for hair loss. Also I'm not sure if the other options have been experimented with as of yet, and there is a chance they might negatively impact growth promoting prostaglandins. We should know more in the coming months as it appears people are going to be trying different topicals to target PGD2.

To be clear, since hair loss is multifaceted I wouldn't put all my stock in just one potential mechanism.

 

[odalbak]

Re: A recently discovered new factor in AA, the cure is near

since hair loss is multifaceted I wouldn't put all my stock in just one potential mechanism.

Sure. But how will we know whether this or that PDG2 inhibitor has any actual effect?

I've personally started to use only SCG eyedrops twice daily, on my scalp obviously. No nizoral, no minoxidil,… nothing except these eyedrops. This is my official debut in self inflicted unpaid guinea pig career. I'll do this untill the end of july (4 full months) and will report here. Don't expect pictures as I don't have a camera.

 

[odalbak]

Re: A recently discovered new factor in AA, the cure is near

Waynakyo, thanks for the link.

I'm not sure of what to do with the information this study displays though.

"Recent studies have demonstrated that Nitric Oxyde production is enhanced in inflammatory vascular lesions".

"We demonstrated that PGD2 suppresses Nitric Oxyde generation in vascular smooth muscle cells".

 

[paul27]

Re: A recently discovered new factor in AA, the cure is near

I saw those eye drops at the pharmacy, Allergen makes them, 10ml for $18.00. How much of it are you applying?