Sm04554

[champpy]

and is it likely that when their phase 2 is actually over, we're going to have another eight+ month waiting period like we are currently having with Bim before we find out any results

[xyz123]

I haven't actually gone over any of the studies so forgive my ignorance...While a lot of these quotes from the studies sound great, please tell me that this has been tested on more than mice and rats?

Actually - I'm not even aware of any animal data for this drug (the animal work was with other Wnt modulators)...

And rumor has it that the Phase 1 results were negative: "Samumed’s Phase 1 trial in Australia was completed and failed to show any hair growth, according to sources at the company. Subjects felt better, but hair counts were no different in the treated vs. placebo groups. To be fair, the study was only one month in duration, so quite short for a hair growth/re-growth trial. This trial will tell if activation of Wnt signaling in the scalp is a potential treatment for baldness." (http://www.hairlosscure2020.com/samu...4554/#comments). Though like Replicel, Phase 1 was for safety and involved just 2 weeks of applying the topical.

Hopefully they deliver on Phase 2 - but we really have no idea - it's all just hype for now. If the results are good, you've got to believe they'll present them at WCH in Miami in November...

[It's2014ComeOnAlready]

Actually - I'm not even aware of any animal data for this drug (the animal work was with other Wnt modulators)...

And rumor has it that the Phase 1 results were negative: "Samumed’s Phase 1 trial in Australia was completed and failed to show any hair growth, according to sources at the company. Subjects felt better, but hair counts were no different in the treated vs. placebo groups. To be fair, the study was only one month in duration, so quite short for a hair growth/re-growth trial. This trial will tell if activation of Wnt signaling in the scalp is a potential treatment for baldness." (http://www.hairlosscure2020.com/samu...4554/#comments). Though like Replicel, Phase 1 was for safety and involved just 2 weeks of applying the topical.

Hopefully they deliver on Phase 2 - but we really have no idea - it's all just hype for now. If the results are good, you've got to believe they'll present them at WCH in Miami in November...

what's the source for that phase 1 rumor?

[xyz123]

what's the source for that phase 1 rumor?

It's in the comments section following a post on sm04554 on the hairlosscure2020 website (link above) - the comment is written by someone named John H. - whatever that's worth...

But I've seen similar comments around the web - i.e. on Paul Knoepfler's website following an entry regarding stem cells for hair loss:

"Paul Frohna, MD, PhD on October 9, 2014 at 11:18 pm said:

The topical drug by Samumed of San Diego, a wnt pathway activator designed to activate the stem cells within the hair folicule, has been tested in a Phase 1 dose ranging study in men with male pattern baldness in Australia. https://www.anzctr.org.au/Trial/Regi...aspx?id=364645 The trial has been completed but no results have been announced, although I heard that the trial didn’t meet its objective efficacy endpt of hair regrowth, but that pts reported a subjective improvement that the company was touting. So, although a small molecule modulator of endogenous stem cells in the hair follicle seems like a great and safe Idea, but it hasn’t worked yet and may never since the biology is very complex."

Paul Frohna seems like a legit guy: https://www.linkedin.com/in/paulfrohna

Anyway - the bottom line is we have no idea if sm04554 is going to work. Even if Phase 1 was completely negative for hair growth - the company must have had some compelling evidence to move forward with two Phase 2 trials. And lacazette highlighted that longer duration of therapy with a Wnt activator can improve results: "A single application to telogen skin is sufficient to stimulate anagen, whereas six treatments not only stimulate anagen of existing follicles but also induce ECTOPIC HF formation".

I'm still really optimistic and believe it could be amazing for regrowth - but it could still be a total bust... We can review the literature regarding Wnts and hair growth as much as we'd like - it's not gonna change anything - we just have to wait...

[lacazette]

In this 2014 human clinical trial they used topical valproic acid (activate B catenin pathway through gs3kb inhibition)

http://www.ncbi.nlm.nih.gov/pubmed/24533507

"Topical VPA increased the total hair counts of our patients; therefore, it is a potential treatment option for AGA."

So b catenin activation seems to work aswell in humans. It makes those recent mouse studies claims more interesting

In HLh forum, a guy who read the entire study, says that the VP acid have just little effect on B catenin activation.

The major question is does the Samumed targeting drug upregulated the wnt activation sufficiently to make the same stunning effects than in those mouse studies?

It's clear that wnt activation will give results on hair, but how stronger they can activate it without taking cancer risks that's the problem?

[Sogeking]

Actually - I'm not even aware of any animal data for this drug (the animal work was with other Wnt modulators)...

And rumor has it that the Phase 1 results were negative: "Samumed’s Phase 1 trial in Australia was completed and failed to show any hair growth, according to sources at the company. Subjects felt better, but hair counts were no different in the treated vs. placebo groups. To be fair, the study was only one month in duration, so quite short for a hair growth/re-growth trial. This trial will tell if activation of Wnt signaling in the scalp is a potential treatment for baldness." (http://www.hairlosscure2020.com/samu...4554/#comments). Though like Replicel, Phase 1 was for safety and involved just 2 weeks of applying the topical.

Hopefully they deliver on Phase 2 - but we really have no idea - it's all just hype for now. If the results are good, you've got to believe they'll present them at WCH in Miami in November...

Sm sounds good in theory however there are too much conflicting information and people jumping to conclusions with wishful thinking.
I'm not sure if they are gonna show us anything in hair loss congress. I guess we'll have to wait and see.
That said I hope Sm is the real deal. I really do.

[nameless]

Sm sounds good in theory however there are too much conflicting information and people jumping to conclusions with wishful thinking.
I'm not sure if they are gonna show us anything in hair loss congress. I guess we'll have to wait and see.
That said I hope Sm is the real deal. I really do.

What exactly do you think we are here at this website for? Do you think that we are here to cure hair loss? Do you think that we are here to cry about hair loss to each other? What do you think the point is to having this website?

I think it's here so we can discuss things related to hair loss, including to share our perspective on what drugs are coming and when. Doing this involves some speculation and I'm sure you would call that "wishful thinking."

To hear you tell it people shouldn't post at all, including yourself. Nobody should even come here. People should just wait quietly until a cure comes to market and have no discussion in the meanwhile. But then why do you come here? Why do you come here when you know that people will be discussing their views about hair loss, cures for hair loss, and timelines for when those cures might come to market?

There is no point for you to come here unless of course you're a phony complaining about other people speculating things about hair loss even as you're doing the exact same thing.

Go away!

[lacazette]

Androgenetic alopecia (AGA), is the most common type of alopecia in men, which is an androgen mediated event. Circulating androgens, including, dihydrotestosterone (DHT), enter the follicle via the DP's capillaries, bind to the androgen receptor within the DP cells and then activate or repress molecular signaling pathways responsible for premature transition from anagen to catagen and follicular miniaturization. This include suppression of stimulatory pathways of Wnt, Stat 3 and Shh and up-regulation of suppressive pathways (e.g., Dickkopf-related protein 1 and BMP 4). Dkk-1, which is secreted from DP cells in response to DHT pathway, is a potent inhibitor of Wnt pathway.[1] BMP 4 protein also acts through the activation of DKK pathway, thereby inhibiting hair follicular growth"

As they explained in the other studies, Wnt pathway activation act like a major signaling cascade regarding the other pathways. And so activate the good ones for hair, and repress the bad ones
Let's just hope that the Wnt upregulation lead by SM04554 will be safely high enough to correct the DHT consequences on these pathways

[xyz123]

Androgenetic alopecia (AGA), is the most common type of alopecia in men, which is an androgen mediated event. Circulating androgens, including, dihydrotestosterone (DHT), enter the follicle via the DP's capillaries, bind to the androgen receptor within the DP cells and then activate or repress molecular signaling pathways responsible for premature transition from anagen to catagen and follicular miniaturization. This include suppression of stimulatory pathways of Wnt, Stat 3 and Shh and up-regulation of suppressive pathways (e.g., Dickkopf-related protein 1 and BMP 4). Dkk-1, which is secreted from DP cells in response to DHT pathway, is a potent inhibitor of Wnt pathway.[1] BMP 4 protein also acts through the activation of DKK pathway, thereby inhibiting hair follicular growth"

As they explained in the other studies, Wnt pathway activation act like a major signaling cascade regarding the other pathways. And so activate the good ones for hair, and repress the bad ones
Let's just hope that the Wnt upregulation lead by SM04554 will be safely high enough to correct the DHT consequences on these pathways

It's amazing how complex hair loss is - so many different biological pathways. It's almost as if someone wanted to make it excessively complicated so that it would be near impossible to treat...

And it's also humbling - despite all of the potential new therapies coming along - how little we definitively know about AGA pathophysiology.

In Cotsarelis' 2011 JCI paper, the introduction stated:

"In AGA, the new lower hair follicle that forms at anagen onset is smaller than its predecessor. Testosterone is necessary for miniaturization, and 5-α-reductase type II inhibitors, which block conversion of testosterone to its more active form, dihydrotestosterone, delay progression of AGA (6). Little else is understood about the cause of AGA"

Now we know that PGD2 is also important. But beyond that, AGA is still largely a black box. Although I'm optimistic, we're really going to have to get lucky for one of these new treatments to have great efficacy. It will happen at some point, but when...

[Sogeking]

It's amazing how complex hair loss is - so many different biological pathways. It's almost as if someone wanted to make it excessively complicated so that it would be near impossible to treat...

And it's also humbling - despite all of the potential new therapies coming along - how little we definitively know about AGA pathophysiology.

In Cotsarelis' 2011 JCI paper, the introduction stated:

"In AGA, the new lower hair follicle that forms at anagen onset is smaller than its predecessor. Testosterone is necessary for miniaturization, and 5-α-reductase type II inhibitors, which block conversion of testosterone to its more active form, dihydrotestosterone, delay progression of AGA (6). Little else is understood about the cause of AGA"

Now we know that PGD2 is also important. But beyond that, AGA is still largely a black box. Although I'm optimistic, we're really going to have to get lucky for one of these new treatments to have great efficacy. It will happen at some point, but when...

I'm telling you that we will create new hair follicles sooner than finding out the root cause of AGA, its mechanism and stopping it.