Kythera - KYTH-105 (setipiprant), other drug now approved (ATX-101)

[burtandernie]

Always keep in mind that 'peer reviewed' merely means that some peers read the article, agreed that the methodology made sense and that it's relevant to their journal. It does NOT mean that they actually verified the results, let alone reproduced them.

True but it says something that everything is out there if someone wanted to reproduce those results. But yeah its not proof it works. When I read what the chief medical officer at the company said below though Im not sure why people are arguing whether it works or not when it sounds like it pretty clearly does. Could they be lying or exaggerating or just mistaken? Sure I guess but no reason to lean that way yet so I dont know if people dont read this or interpret it differently than I do. It sounds like it works.

"These observations are potentially the most innovative new thinking in hair loss over the last two decades. Setipiprant is believed to directly affect this hair loss pathway, and our own preclinical and in vitro human hair models confirmed this effect. It is a well-characterized molecule with a large safety database and we believe we can quickly initiate a development program to study it in hair loss. - See more at: http://globenewswire.com/news-releas....GQ9tOIXk.dpuf

[walrus]

if you have in vivo observational evidence on humans then please present it in the form of a double placebo controlled trial? Perhaps I have missed it.

Perhaps you overlooked that an inhibitory effect of PGD2 on hair growth mediated via the GPR44 receptor has been experimentally demonstrated in explanted human follicles. Given that this evidence was convincing enough to secure up to $27 million in funding for further research and development---I guess the investors didn't deem it necessary for a double blind placebo controlled trail to 'believe in the whole PGD2 hypothesis' either .

You do understand that Garze & Cotsarelis both concur that it might not work and the pathology of AGA might not be based around prostaglandins and work downstream thus be an unimportant factor? After all that is how a hypothesis works.

I quote from the abstract of Garza et al., Prostaglandin D2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia, Science translational medicine, 2012, Vol. 4, Issue 126:

These results define PGD2 as an inhibitor of hair growth in AGA

Do you refute this claim? While they concede that multiple mechanisms may well be responsible for hair loss in AGA---this does not negate their findings.

Always keep in mind that 'peer reviewed' merely means that some peers read the article, agreed that the methodology made sense and that it's relevant to their journal. It does NOT mean that they actually verified the results, let alone reproduced them.

I am familiar with the peer review process having published papers in such journals myself. Usually the editor will first decide if the paper is relevant to the journal before commencing with peer review. The quality of comments can vary but they do NOT simply need to agree on whether the methodology made sense. Obviously they do not reproduce an entire experiment (though results often can be if data and analysis code are made available as they increasingly are), rather if results are worth further investigation that follows in subsequent work and possible publications. Any aspect of a manuscript is open to criticism while under review. Peer review is not a perfect system, but it is more trustworthy and credible than the opinion of unqualified anonymous users on an internet forum such as this.

[Swooping]

Perhaps you overlooked that an inhibitory effect of PGD2 on hair growth mediated via the GPR44 receptor has been experimentally demonstrated in explanted human follicles. Given that this evidence was convincing enough to secure up to $27 million in funding for further research and development---I guess the investors didn't deem it necessary for a double blind placebo controlled trail to 'believe in the whole PGD2 hypothesis' either .



I quote from the abstract of Garza et al., Prostaglandin D2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia, Science translational medicine, 2012, Vol. 4, Issue 126:

Do you refute this claim? While they concede that multiple mechanisms may well be responsible for hair loss in AGA---this does not negate their findings.

Actelion will be eligible to receive up to $27 million in potential development and regulatory milestones

I know these studies, don't worry. Besides that 27 million isn't really much in the pharmaceutical sector. Up to 27 million doesn't mean that their initial transfer was that high too. Actelion wanted rid of the compound anyway because it lacked horrible in efficiency for their respective trials.

- Anyway.. Explant hair follicle vitro model? What about DKK-1? What about TGF-B2? What about P-53? What about SUR2B? We can go on.. All of these stop elongation in an in vitro hair explant model as shown by peer reviewed papers. Does that mean that acting on these pathways will act as a maintenance treatment too? Elaborate please.

- What do you think of the consensus between many researchers lately which started basically with the outlines of Philpott in 2007? Followed up in several studies by Yang, Domyati, Upton, Mj Lee etc. Namely an altered cell cycle fate orchestrated by major regulatory pathways induced by ROS/DNA damage. Doesn't the evidence for the pathology of AGA of these studies look way more logical to you? If so why not? Elaborate please.

- There is no genetical evidence for prostaglandins in AGA; http://s23.postimg.org/pn1r4ooy3/pgd2genetic.jpg.

I'm not disregarding their research and findings walrus. I'm saying that I concur with other researchers and find it unlikely that they are on the right end with their hypothesis. Other researchers lately show a whole other picture of the pathology of AGA than Garza & Cotsarelis have done. In fact nobody really even followed up the research of Garza & Cotsarelis. Odd, to say the least.

We can't extrapolate data from in vitro or in vivo rodent models to humans and assume it will work. That's ridiculous right? I can show you tons of other factors over expressed in scalp and as said tons of other compounds that stop hair elongation in vitro.

Does that mean that it works upstream or will be a valid therapeutic treatment? Obviously not. That's why they have a hypothesis. In the POC trials they are now going to check to what extent that hypothesis is valid.

Whether Cotsarelis is right or the mass of other researchers are right remains to be seen. We will only get to know that when we see the results of their clinical trials. Till then you don't know and I don't know. Unless you are a clairvoyant? Simple as that. I have a opinion, that doesn't mean that I'm on the right end.

Anyway I'm still genuinely interested if you can elaborate on the first 2 points I asked you.

[Swooping]

Straight from Garza his mouth(1) btw walrus;



(1) http://www.ncbi.nlm.nih.gov/pubmed/24521203

[Arashi]

Peer review is not a perfect system, but it is more trustworthy and credible than the opinion of unqualified anonymous users on an internet forum such as this.

Of course I dont disagree with that. However I think, we as a hairloss community, should realize very well that reviewers usually dont reproduce the science. Especially when there are commercial interests, like it's an article about some substance or surgical method the researcher is going to bring to the market, we should be VERY VERY wary ...

[KO1]

I would not dismiss the Pgd2 hypothesis so quickly. As for in vivo results, do you recall Cots description of mice that over express ptgds? They showed hair follicle miniaturization and sebaceous gland hyperplasia. Sounds familiar no? That said, it doesn't mean that blocking pgd2 will be a game changer.