FGF5 ablation vs FGFR1/2
Fgf and Wnt signaling interaction in the mesenchymal niche regulates the murine hair cycle clock
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FGF5 ablation vs FGFR1/2
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Forgive my ignorance I have a ton going on in life... however; would Samumed (currently Phase 3 which should be done in a few weeks) not fit into this equation??
Im suprised that SM is not a hot topic in this section of the fourm. Phase 1/2 showed literally no serious sides and growth of new follicles as well as thickening of existing hairs and increase in Anagen via WNT pathway!!!
clinicaltrials.gov
Im suprised that SM is not a hot topic in this section of the fourm. Phase 1/2 showed literally no serious sides and growth of new follicles as well as thickening of existing hairs and increase in Anagen via WNT pathway!!!
ClinicalTrials.gov
clinicaltrials.gov
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AFAIK SM doesn't do anything to upregulate R-spondins. The point of Wnt upregulation is to increase b-catenin accumulation in the nucleus. Wnts are just a part of that pathway, so not a full solution unless you actually injected Wnt proteins daily. SM is just a part of the solution, and it's really not novel to us on the boards. We've been experimenting with Wnt agonists for over a decade.
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Seeing you know mustang why dont you try topical duta instead of finasteride? finasteride will be guaranteed to go systemic whereas many avoid that on topical duta 1x/week.
Could SM04554 potentially be strong enough to provide long term maintenance you think?
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I get a laxative effect from Topical Castor Oil on my Scalp at a Molecular Weight of 980 lol.... So I am fully prepared to try finasteride at a micro dose at a Molecular Weight of 270 or 370 whichever one it is.... Duta at 580 is going to go straight thru my pouros *** scalp regardless of Molecular Weight... I would rather just block 5AR Type 2/3 via finasteride which are not found in the Brain (Type 1 is) where as Duta also blocks Type 1.
I fully expect finasteride to go systemic; but at least get as much of a localized effect on Scalp 5AR topical application....
As I stated I was taking 1.2g daily of herbal estrogens in Saw Palmetto and Foti 600mg each daily which caused water retention in abs and chest. upon dropping I had a huge surge in Androgens (DHT) which noticably thinned out my hair and body thankfully went back to normal with no permanent Gyno etc...
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@pegasus2 I deleted my prior post as I finally took time to read over everything discussed in this thread coherently... Hopefully we get SM04554 sometime next year as I would love to start using that along with a FGFR silencer... I know you said that FGFR has to be competely silenced for the Supercharged growth effect...
I am interested in seeing if the super low dosing of Infigratinib topically has any side effects... I still need to look into this further and weigh the risk reward etc... However; do you not think Fulvic Acid providing even a partial supression of FGFR would not provide any benefit?
As of right now I looking forward to getting SM or something similarily efficacious and coupling that with Fulvic Acid and seeing what happens... What Wnt Agonist are you going to use with Infigratinib?
Cheers!!
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If fgfr antagonists do work, then it would probably work to a degree. FGFR expression increases throughout anagen until it hits the threshold where it inhibits RSPO. Any inhibition of FGFR would theoretically delay reaching that threshold and keep hair in anagen longer. This is assuming that the positives of fgfr inhibition outweigh the negatives.
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@pegasus2 seeing you seem to be in the right head space and have a firm grasp of this area at the moment; maybe you could help us understand if any of this recent research could help us in putting together the ultimate gene transcription stack. I honestly rank Wnt signaling + other gene transcribing ompounds as the only thing worth talking about in this section.... If its not 5ARI, Min, Dermarolling etc; this is the next big think on the horizon as both SM04554 should be ready soon and PTD KY is starting trials next year. I know there was a group buy of Chois first PTD compound that didnt do anything for the participants but I highly doubt a random lab in Canada perfectly synthesized the compound to the precise efficacy of Choi's lab. Maybe if it was already on the market the could easily back engineer it; unitl then your playing roulette trying to clone something off of limited data.
Skin Regeneration Regulators. Source: Bernaskie Lab GitHub.
The research is shared on GitHub. Also see Biernaskie Lab. According to the findings, Runx1, retinoic acid, and Hic1 control mesenchymal regenerative capabilities.
According to this summary, Dr. Biernaskie (whose work I have covered in the past) said that they have shown the following:
LEF1 gene expression in fibroblasts has the potential in adult skin to repair itself like the skin of a newborn baby. This skin can also grow new hair follicles.
Interview with lead author Dr. Ryan Driskell.
“We identified a genetic factor that allows adult skin to repair itself like the skin of a newborn baby.”
Skin Regeneration, Wound Healing and Hair Growth | Hair Loss Cure 2020
Skin regeneration and wound healing are closely connected to hair follicle regeneration. If you can regrow scarred skin, you can regrow hair.
www.hairlosscure2020.com
New Studies on Skin Regeneration and Wound Healing
1) In September 2020, a team that included Dr. Jeff Biernaskie published a study on the regenerative potential of dermal fibroblasts during wound healing. They identified a specific population of progenitor cells that reside within the dermis and which aid in wound healing.The research is shared on GitHub. Also see Biernaskie Lab. According to the findings, Runx1, retinoic acid, and Hic1 control mesenchymal regenerative capabilities.
According to this summary, Dr. Biernaskie (whose work I have covered in the past) said that they have shown the following:
2) Also in September 2020, a new study from the University of Washington identified Wnt transcription factor Lymphoid enhancer-binding factor 1 (LEF1) as the key factor in adult skin regeneration.
LEF1 gene expression in fibroblasts has the potential in adult skin to repair itself like the skin of a newborn baby. This skin can also grow new hair follicles.
Interview with lead author Dr. Ryan Driskell.
“We identified a genetic factor that allows adult skin to repair itself like the skin of a newborn baby.”
That study doesn't really give us any new practical information as far as I see. TCF/LEF is downstream of Wnts and b-catenin. LEF1 is a known marker of Wnt activity, its significance isn't anything new. We need to maintain b-catenin accumulation in the cell nucleus to activate TCF/LEF and modulate downstream target genes. You're on the right track with the Wnt pathway, it's just a question of how do we keep it upregulated in bald scalps, and without causing cancer? Clearly GSK3b inhibition alone is not enough to restore normal Wnt signaling or we would get better results from it. PTD-DBM is great in the lab, but it's not practical for home use. That's why no one got results from it, and they are testing KY19382 now. The Wnt pathway is conserved, there are negative feedback loops that keep us from developing tumors. When it gets broken, as in Androgenetic Alopecia, it's tough to restore it. You are looking at targeting GSK3b, SFRP1/2, DKK1/2, CXXC5, ZNRF3. What happens then if you successfully shut off every control mechanism? You probably grow significant amounts of hair, but do you end up with tumors as well?
WNT sure looks like the most important one. But FGF and shutting off TGF-b as well as BMP is also important. Guess what the inhibiton of the DVL-CXXC5 PPI does in combination with GSK3-b inhibition? All that. KY's gonna be it.
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Probably??? Not so easy
What happened here? any update?
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Just started this month as I took a break. Will report in a while.
Good luck.
Also, can anybody explain if Resveratrol is an inhibitor or an activator of Wnt pathway ? I searched but I found very contradictory infos in scientific literature. Some studies say it's a "good" Wnt agonist and some others say the exact opposite. Does it depend of the progenitor cell type ?
Resveratrol promotes anagen, and it's good for your overall health, so I wouldn't stop taking it. You probably know its bioavailability is poor, so it may not do much in humans.
We had to wait for it to be made so I just got it recently. I will start it soon, but I'm not expecting too much from it. Downregulating fgf9 and fgf7 signaling is counterproductive so this isn't the best method of upregulating RSPO, but it's about the only option we have at the moment.
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Totally. I am a bit nervous using it. So I'll monitor closely.
Started it today at 1mg/day. I will let you know if I go bald lol