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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
Samumed Sm04554 Results Normalized To Baseline
- Thread starter hypetraintime
- Start date
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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I'm just telling you my opinion based on my own research. I'm sorry, but I really don't have time to link a dozen studies and write a page on why this method won't restore Wnt signaling to pre-Androgenetic Alopecia levels.
Yes, this seems to have a more lasting effect than minoxidil but it's only 45 days. I promise you it's not permanent. It might even be a fluke due to timing of the trial and seasonal sheds. You will see results taper off with this as well 3 months after discontinuation.
It actually is certain that minoxidil is targeting the Wnt pathway indirectly. You can't grow hair without upregulating it, and there are studies confirming minoxidil upregulates the canonical Wnt pathway. There is no single method by which it does that, but upregulating PGE1/2 is one of them, along with inhibition of GSK3b. None of these drugs are going to work long-term without stopping DHT. It's not as simple as just inhibiting GSK3b or DKK1/2. If SM restored Wnt signaling to pre-Androgenetic Alopecia levels then it would have grown more than 10 hairs.
Wnt disinhibitors have been tested in various studies too, not just on the forums. Will you also discount those? You are even discounting Samumed's own trial which showed an improvement of 10 hairs. In a recent trial minoxidil showed an improvement of 22 hairs over the same 4 month period. SM is just glorified lithium.
Sorry, but people getting their hopes up for this will be even more disappointed than the CB crowd. If you'd like to place a wager though, I'll take the free money.
Yes, this seems to have a more lasting effect than minoxidil but it's only 45 days. I promise you it's not permanent. It might even be a fluke due to timing of the trial and seasonal sheds. You will see results taper off with this as well 3 months after discontinuation.
It actually is certain that minoxidil is targeting the Wnt pathway indirectly. You can't grow hair without upregulating it, and there are studies confirming minoxidil upregulates the canonical Wnt pathway. There is no single method by which it does that, but upregulating PGE1/2 is one of them, along with inhibition of GSK3b. None of these drugs are going to work long-term without stopping DHT. It's not as simple as just inhibiting GSK3b or DKK1/2. If SM restored Wnt signaling to pre-Androgenetic Alopecia levels then it would have grown more than 10 hairs.
Wnt disinhibitors have been tested in various studies too, not just on the forums. Will you also discount those? You are even discounting Samumed's own trial which showed an improvement of 10 hairs. In a recent trial minoxidil showed an improvement of 22 hairs over the same 4 month period. SM is just glorified lithium.
Sorry, but people getting their hopes up for this will be even more disappointed than the CB crowd. If you'd like to place a wager though, I'll take the free money.
I've also taken dutasteride for 5-6 years now and I was never able to maintain, I'm moderately diffusing all over my scalp. This year I saw the wrath of it when I lowered my dutasteride dose to 4x a week (due to my financial situation) and my hair loss just accelerated at a ridiculous pace.
I've never been able to maintain ever since my hair loss started at 16 and I'm hoping in the future a combination of dutasteride, CB-03-01 and SM04554 will give me maintenance, I'm not expecting any regrowth mostly because nothing I have ever tried has ever regrown any hair... I'm just hoping for maintenance.
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My hair loss also started at 16, 22 now, how old are you? this and dermarolling / minoxidil are my last hopes pretty much everything I’ve tried has given me bad side effects or I’d be on sh*t like propecia / dutasteride. Currently Norwood 3 and diffuse loss starting to look bad
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well smh... there goes my high hopes for SM.. .well, actually if it is a weak side effect free version of minoxidil ill take it. No heart issues, collagen degredation etc...
@pegasus2 or anyone else who understands the method via which KY works; it would be nice to start a thread regarding that or just post it here I guess. What exact mechanism does that supposedly work on and is that at least more of a hope based on your understanding of the science... sigh...
@pegasus2 or anyone else who understands the method via which KY works; it would be nice to start a thread regarding that or just post it here I guess. What exact mechanism does that supposedly work on and is that at least more of a hope based on your understanding of the science... sigh...
25.My hair loss also started at 16, 22 now, how old are you? this and dermarolling / minoxidil are my last hopes pretty much everything I’ve tried has given me bad side effects or I’d be on sh*t like propecia / dutasteride. Currently Norwood 3 and diffuse loss starting to look bad
@pegasus2
Do you reckon it would be pointless to combine SM04554 with Minoxidil since Minoxidil is already known to work on the Wnt pathway?
Is there anything currently in clinical trials that you reckon can compete with minoxidils efficacy?
If dutasteride and minoxidil maintains
KY is more promising. It targets cxxc5 and GSK3b. Without knowing the full MOA for SM it's impossible to say for certain that KY will be better, but given KY's MOA I would expect it to outperform SM's phase 2 results.
Bayer's prolactin antibody is promising, and KY might be more potent than minoxidil. There's a very promising r-spondin agonist that might be used for hair someday, but the startup behind it seems to be focused on other diseases. The future is bright for our children, but it's going to be a long wait for us.
Right, at least SM may be a more tolerable drug than minoxidil, and effective in minoxidil non-responders.
KY is more promising. It targets cxxc5 and GSK3b. Without knowing the full MOA for SM it's impossible to say for certain that KY will be better, but given KY's MOA I would expect it to outperform SM's phase 2 results.
It's worth using both. Minoxidil has a broad range of actions, while SM is more targeted. It's probably considerably more effective at GSK3b phosphorylation than minoxidil.
Bayer's prolactin antibody is promising, and KY might be more potent than minoxidil. There's a very promising r-spondin agonist that might be used for hair someday, but the startup behind it seems to be focused on other diseases. The future is bright for our children, but it's going to be a long wait for us.
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How would you integrate SM with a microneedling protocol? Every day or just 3 days after wounding?
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Yeah I read that study and it upset me since I follow the follica patent. I wonder if Follica has taken this into account. Theoretically the macrophages are activated immediately after the 15th day, therefore in conjunction with the new wounding session. SHH is the key, unfortunately I haven't yet been able to find a safer agonist than SAG other than minoxidil + a.azelaic pairing
What's the problem? Not enough interest?
Yeah sure. But I'm still interested by SM as it appears that the more young you are and the more hair you have => the more regrowth you get. So SM might be helpful for a subgroup of patients (young and >NW3, maybe more if you're lucky) as in this subgroup, regrowth was approximatively equal to minoxidil's responders rate.
+ thanks to Pegasus for taking time to explain all of this, really useful for general knowledge.
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This plus dermarolling is as close to a cure as it gets.
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We will know in five years bro...
Follica tried a similar compound with wounding, and the results were not good. Dermarolling plus minoxidil was superior. I think it's time to ignore this thread, as people just keep repeating the same copes and hopes every few pages.
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If it don’t work in someone who tried it, you really think this is a cure? It will be a treatment that have so much variation in efficacy like minoxidil.