Topical JAK inhibitors definitely work for androgenic aloipecia -- Big Development

[Swoop]

BTW Swoop, I may be wrong about this, and if I am, then never mind, but I believe you said at some point about CB that will never match the effectiveness of 5-AR inhibitors. Or that might've been about Setipiprant. Either way... why wouldn't something like CB (or anything else that completely blocks the androgen receptor) be equally effective (if not more, actually, since it would prevent ALL androgens from binding to it) than Finasteride?
Provided that DHT only works at the androgen receptors and no where else.

So far it seems that based on effectiveness RU is worse than Finasteride, and CB even worse than RU, and it doesn't sound right.

If compounds like CB-03-01 or RU58841 would actually be able to completely block the androgen receptor then that would be great, or rather block all androgens from binding. Problem is they can't.

For instance if we look what is said about RU;

RU58841 is an androgen receptor (AR) inhibitor capable of blocking 70% of DHT binding

So who knows how much it actually blocks in-vivo? For all you know it might block 40% of DHT in some and in other people 70%. At the very least we can say with certainty that it doesn't stop all androgens from binding. I have read quite some literature of androgen receptor inhibitors and it is a complicated and hard task to block all androgens from binding and actually pretty much no compound till date has achieved of being a full inhibitor of the androgen receptor. Recently Dench57 came up with ODM-201, which is one of the newest generation androgen receptor inhibitors which might come close to really stop all androgens from binding. We need one that like that but one doesn't go systemic with a good safety profile.

I might have said that dutasteride > finasteride > RU > CB? In a head to head hair count trial over a longer time I think that would be the case. I can't know for sure though, that's my rough prediction on the data. Still I would put all of those treatments in a tier 1 box. CB-03-01 should have the advantage of having a very good side effect profile though like you know, we'll have to see .

 

[NewUser]

You forgot that they also have to develop the special topical formulation for Androgenetic Alopecia so add 2 years.

I'm guessing but i think they will do trials for Androgenetic Alopecia in parallel with All the other types of hair loss. They now have about half a dozen reasons to hypothesize that it may work for Androgenetic Alopecia whereas they had none before. She mentions the 3D spheroid delivery formula they used in getting the results that they did. Christiano said last October that more work is needed to develop that topical formula.

- - - Updated - - -

The disrespect is real.

I understand your pain, however, I believe you are woefully misguided with respect to who is directly responsible for the disrespect. Angela Christiano, Claire Higgins, Colin Jahoda et al the people listed on the report published last October are among the few friends balding people actually do have. And they don't have deep pockets like big pharma actually does have. Instead, big pharma chooses to ride the coattails of old drug discoveries because that is what the Reaganauts and Mulroneyites to present day have allowed them to get away with. The conspiracy runs much deeper down the rabbit hole than some people are willing to recognize I think.

 

[Swoop]

This is funny, so I made this post right; https://www.hairlosstalk.com/intera...aloipecia-big-development.99308/#post-1334543.

A few days later that CEO of the company says this on a conference;

We are going to develop a topical JAK inhibitor, we know that a systemic JAK inhibitor doesn't work in this indication. And there is actually a pretty good reason for that. You can't achieve the right concentration... When you think about the drug going through the superficial dermal plexus, it can't migrate up to the hair follicle bulge. So in AA it works because it works at the hair follicle bulb which is deeper down and more accessible through systemic circulation. Drug doesn't normally migrate up, so you have to go through the opposite way and go topically through the hair follicle, and we have actually shown this through pre-clinical models.

First of all this indicates again that they have only shown this through pre-clinical models in the rodent model as I have shown. Meaning that there is no evidence of this doing anything for Androgenetic Alopecia.

Also what he argues there is pretty funny. It's actually not a pretty good reason, it is a very weak reason imo. It is along the same lines of my message but I argue that the right concentration will suffice by systemic administration in the whole hair follicle. Let's be honest there. First of all the distance between the bulb and bulge especially in a miniaturized hair follicle is extremely small. Makes his message very doubtful already.

More importantly are the observations of Vitiligo however which takes place in the most superficial layers of the skin. This would be above the bulge level of the hair follicle level. Systemic JAK inhibitors do work when taken systemically for Vitiligo;

So wait systemically the drug can concentrate itself around the bulb as evidenced in AA and in the most superficial layers of the skin as evidenced in Vitiligo... But not in the bulge which is on a extremely small distance from the bulb anyway and below the most superficial layers where Vitiligo takes place?

Also "drugs don't normally migrate up". Yeah sure they don't.... .

I call biggest bullsh*t ever lol based on this very simple reasoning already. JAK inhibitors are going to do JAK sh*t boys. It gets more clear and clear to me that you shouldn't always listen to what these guys say, whether it's a researcher or a CEO of company. Very often they will speak from a huge bias perspective, to attract investors, hype, interest etc.

 

[Afro_Vacancy]

Isn't there an obvious reason to go topical?
I thought these compounds had a lot of side effects?

 

[Swoop]

Isn't there an obvious reason to go topical?
I thought these compounds had a lot of side effects?

Yes. To limit systemic activity for something like AA and Vitiligo. Especially when it's not severe. If your AA is localized and not severe then it makes sense to make a topical to limit systemic absorption. Same for Vitiligo... If you have one spot somewhere on your face then it makes sense to rub it in with a topical and profit from less systemic absorption and thus limit side-effects. However when Vitiligo is extremely severe (spots all over the body), it doesn't make sense to make a topical but it's better to actually go through the systemic route. First of all because it's not practical to rub your whole body with a topical and secondly when you will rub to much of the topical adequate systemic absorption will happen probably anyway. This is also the angle Aclaris seems to vouch for (less severe = topical , severe = systemic). They will trial both topical and systemic versions AFAIK.

Don't get me wrong. This has been a great discovery for people who suffer from AA, Vitiligo etc. It was very clever. However we need to profit from something that works for Androgenetic Alopecia. And that's where that reasoning is so damn weak of JAK inhibitors having potential for Androgenetic Alopecia topically but not systemically. It doesn't make sense at all.

 

[Pray The Bald Away]

JAK inhibitors are going to do JAK sh*t boys.

Fuckin LOL. I'm laughing but simultaneously dying on the inside!

 

[tryringtomaintain]

Has anyone used any JAK inhibitors this year and had success??

 

[alscarmuzza]