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Samumed Sm04554 Results Normalized To Baseline
- Thread starter hypetraintime
- Start date
- Reaction score
- 107
Will there be an oral form of any wnt drugs?
I'm guessing there is no way to safely deliver it to the scalp that's why it is topical, however wnt is a pathway targeted for aging as well and that is systemic, so theoretically an oral form of this should be available right?
I'm guessing there is no way to safely deliver it to the scalp that's why it is topical, however wnt is a pathway targeted for aging as well and that is systemic, so theoretically an oral form of this should be available right?
Even though in both trials they are targeting wnt pathway, they're doing it with completely different molecules and consequently in different ways.
Think about RU and CB, the working principle is the same but CB seems to have a much better safety profile.
All the questions will be answered in roughly two months, but even now i think it's wrong to associate side effects of two different molecules in two different parts of the body just because they both target wnt pathway.
Maybe we will have a perfectly safe drug, maybe it will cause cardiac arrest, we don't know yet, but believe me, both efficacy and side effects have nothing to do with other drugs in samumed's pipeline.
This is wild speculation.. The thing to take into consideration here is the people reviewing this at the FDA or EMA will be much more qualified than us to evaluate safety, let's see what they have to say first.
+ lorecivivint has the opposite effect of SM04554 ( downregulates Wnt expression ).
Saying "SM04554 would cause cardiac arrest because lorecevivint did and because they target the same pathway." is the same as saying "Andractim would cause sexual impotence in men because Finasteride did and because they target the same pathway.".
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- Reaction score
- 1,242
Hopefully more hair...
I wanted to ask you something : Do you think apply some slight fgfr downregulator like Ferulic Acid could improve SM04554 results or even Minoxidil results ?
In theory.
- Reaction score
- 273
a
sorry to bother you with that but as you are one of the most knowledgable here are you somewht hopefull for sm results or do you think it will be weak at best? i'm honestly desperate and about to give up as my genes are too shitty to allow m to win that battle but do you think it could ar least give us with severe hairloss and non repsonder to dutasteride and anti androgen in general maintenance? thanks
People who don't respond to dutasteride probably won't respond to anything short of full hrt. At least as far as what's currently or soon to be available.
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- 273
thxsso i guess i'm fucked.... i had high hopes for sm
Eh before you give up entirely, can you elaborate on what you define as a non responder to dutasteride? Do you feel it has no effect on your hair whatsoever or is it that you can't maintain with dutasteride alone?
A combination of dutasteride, RU or CB and SM04554 may be enough to help you maintain.
- Reaction score
- 273
took dutasteride for 2 years and my hairline just kept on receeding just like when i was on finasteride before ( my twin haas been on dutasteride for 5 years now and it's the same for him he only maitains cause he is using nuclear dose of topical min + oral min which is ruining his face).
tried low dose ru beore but honestly i'm too far gone and already hypogonadal and eligible for trt tbh my genes are too subhuman to win that fight as i know if i hop on trt the test will ruin my hairline and i'm not willing to go on high dose of RU+ dutasteride just to see if i could maintain so as much as i'll look even more hideous with no hair i think i got no choice ( turning into a woman for a few hair or giving up :/)
got some additional bloodwork to do tomorow to decide if i want to get on trt so i' waiting for sm results and maybe going to try a low dose ru and topical dutasteride just to see in the meantime.
Maybe it will be easier for you to clean your diet, IF, exercise, and slow the aging process so that you'll still be young when something better comes to market.
You keep saying that dutasteride and finasteride non responders will not be able to get results neither from SM-04554. They work on two different aspects of Androgenetic Alopecia, so i don't see why one's efficacy would exclude the other's.
What i understood, as much as my limited knowledge allowed me to, is that Androgens don't make the damage themselves, instead they change something in the hair growth cicle and this then leads to miniaturization. This "something" (or at least the main responsible) appears to be the wnt pathway, which is downregulated by the action of androgens. Being able to upregulate it back to physiological levels means attacking Androgenetic Alopecia a step further from androgens receptors. It's like saying "You, DHT, do what you want, since you will not be able to screw hair growth cycle anymore!". So we could have a scalp full of dht and other androgens of every kind, hair follicles packed with androgen receptors in the worst way genetics could imagine it and no effect on the hair growth cycle, because we are keeping wnt pathway to physiological levels thanks to this drug.
This, at least, is what i've understood, based on the relevant studies in this matter.
Being no expert at all, i will be really happy to learn if something, if not everything in my current understanding is wrong and discuss about it.
I have no intention to judge your opinions, but just to understand your point and discuss.
- Reaction score
- 273
yeah that's how i cope for now on if i decide to give up on hair for good i'll be hideous but at least i'll be wrinkles free:/
i'm afraid wnt is just one of many more underagulated pathway in male pattern baldness unfortunnately
SM is not a true Wnt agonist, it's a Wnt disinhibitor. It can't keep Wnt/b-catenin translocation at pre-Androgenetic Alopecia levels. If you periodically inject Wnt3/7/10 proteins, FZD4, LRP5/6, and RSPO2/3, then I imagine Wnt signaling would stay high even in the presence of DHT because you're artificially increasing it. All SM does is target one or maybe two of the inhibitory factors. It's not enough to fully restore Wnt signaling even in the absence of DHT. This isn't the first drug to upregulate Wnts. A lot of them have been tried on the forums with limited success, going back 20 years. Minoxidil ultimately works by upregulating the Wnt pathway, and its results are similar, but better than, the reported results for SM. So when it comes down to it minoxidil effectively has the same MOA as SM, only more potent, yet it can't even maintain hair for 1/5 of the time that dutasteride does. So why would SM do any better? It won't. If dutasteride doesn't work for you then the best SM will do is buy you an extra couple of years, same as minoxidil.
I thank you for the quick and articulated response.
There are some points i'd like to discuss more about:
Is what you are saying about it not being able to restore and keep normal wnt signaling based on some evidence or is it an assumption based on clinical efficacy from the phase 2 study?
Minoxidil MOA is yet not fully understood.
"The therapeutic mechanism of minoxidil action in Androgenetic Alopecia is uncertain, but a number of possibilities, including vasodilation [13], angiogenesis [14], enhanced cell proliferation [15], modulation of potassium channel conductance [16] and regulation of prostaglandin [17, 18], have been proposed."
The theory of a different MOA is also confirmed by the totally diverse response once application of the two topicals is suspended: one, minoxidil, leads to a rather violent effluvium that will erase every progress gained, the other, at least from the data gathered from phase 2 study, is showing an incremental hair count up to 45 days since the last application.
Even assuming minoxidil is actually targeting wnt pathway (which is far from certain) it is clear that there must be something different in the way the two are doing it, so every comparison between them i find to be nonsensical.
The bit about similar wnt targeting drugs tested in this forum before i will not discuss, since i prefer to base my assumptions (which are nevertheless speculations) only on trustworthy sources and regulated studies and not DIY experiments (which, by the way, i don't judge).
In conclusion, i think it is too early both to doom this to a "less-than-minoxidil-2- years-giving" drug, and to proclame it the breaktrough in hairloss drug development that will give you a Norwood countdown.
It has showed promising results in phase 2 study but the real answers will follow the publications of the phase 3 results.
Even the fact alone that it has reached and completed phase 3 is an incredible news and a probable indication that this drug has some potential to unleash.
I hope this post won't make me a fool in a year or two
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