Bayer Prolactin Receptor Antibody For Male And Female Pattern Hair Loss

[Otrebor]

Posting this human study again for the people who have forgotten about it or never read the whole thread. Some Canadians claim that experimenting with sulforaphane(broccoli sprouts) is more scientifically valid than PRLR antagonists, but there is zero indication in the scientific literature that sulforaphane or NRF2 is responsible for the pattern of hair loss found in Androgenetic Alopecia. There is for prolactin. That's not to say that NRF2 activation isn't helpful, but it is not a lack of NRF2 activation that causes Androgenetic Alopecia so it cannot cure it.

"PRL represents a promising candidate gene for the hair growth defects observed in Androgenetic Alopecia-affected HFs. Moreover, PRL stimulates adrenal androgen production and elevated PRL levels have been reported to be accompanied by hirsutism and hair loss from the scalp, which resembles the pattern observed in Androgenetic Alopecia.[74-76] Also notable in the context of Androgenetic Alopecia is the observation of sex- and location-dependent hair growth regulatory effects for PRL in studies of human ex vivo HFs. While PRL promoted hair growth/hair shaft elongation in HFs derived from female frontotemporal scalp, PRL treatment of isolated male occipital scalp HFs resulted in premature catagen induction and thus the inhibition of hair growth.[77] This observation has been further substantiated on a molecular level, since PRL treatment resulted in sex‐ and site‐specific differences in gene expression.[77] Furthermore, analyses of plucked HFs from male frontal and occipital scalp revealed differential expression for several microRNAs (miRNAs) that target PRL signalling.[64] Together, these findings suggest that PRL action may contribute to the observed differences in Androgenetic Alopecia susceptibility between frontal and occipital HFs and the resulting characteristic hair loss pattern"

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onlinelibrary.wiley.com

While I think that broccoli sprouts are too weak to be of any use, I do think more potent NRF2 activators are worthwhile. It improves both hair and skin. I posted this patent last year for oltipraz:

"Fibroblast population in the dermis of the Oltipraz treated group was significantly higher than that of the control and vehicle groups. Fibroblast population in Oltipraz treated group was reported 92.29% higher than the controls (p=0.003) and 104.25% higher than the vehicle group (p=0.003).The volume density of the collagen bundles was 38.03% and 57.75% higher in the oltipraz treated group compared to the control and the vehicle groups, respectively, which both were statistically significant (p<0.001). Consequently, the volume density of hair follicles was higher in the oltipraz group in comparison to the control (66.1%; P=0.043) and the vehicle (210%; p=0.001) groups"
https://patents.google.com/patent/KR101165648B1/en

I think it's more useful for hair pigmentation than hair growth, but it should help both.

How is it possible that oltipraz is an inhibitor of hif1a when it is known that it activates cell proliferation in hypoxia, damn it's really hard to look for a square in this pathology

on the other hand, on prolactin, is it established that there is a direct relationship with androgens or does it act through other common pathways with androgens?
if the first we are still screwed, you can not mess with androgens

 

[Ralph Wiggum]

So, it's over?

Sorry, how is it over?

 

[pegasus2]

e.g. "finasteride grows X hairs per cm^2 in macaques, but Y in humans"
e.g. can we use it to estimate the % of hair loss in macaques that has non-androgenic causes and assume it won't translate to humans?

It's pretty much 1:1. I don't know where you got this idea that Androgenetic Alopecia is so different in macaques, but it's not supported by the literature. I already did the math in this post. We can estimate from the aforementioned study that finasteride increased terminal hair counts by up to 12.8/cm² in stumptailed macaques after 6 months versus 113/cm² for HMI-115. Per the following study finasteride increased hair counts in humans by 77 hairs in a 1 inch circle at 6 months. That's 15.1/cm², so slightly more than in the macaque study. Probably dead even because for this conversion I only calculated the maximum number of terminal hairs from the hair weight. It is likely a combination of terminal hairs and vellus hairs, which would likely mean finasteride increased terminal hair count in macaques by <10/cm², but increased total hair count by appx 15/cm², so pretty much exactly the same as in humans.

For an apples to apples comparison without any conversions, finasteride increased hair weight in humans by a net 25.6% compared to net 23% in macaques. It's not a guarantee, but based on the available evidence it is likely that HMI-115 will have approximately the same efficacy for Androgenetic Alopecia in humans that it does in macaques.

 

[Bread24]

So, as far as i read the tenor here is negative? I read about the whole thing being over and gone, to that this is the end of this nightmare...
Would someone be so nice an sum up where all this is right now?
As far as i see, Hope Med wanted to start the trails this year, but there is basically no communication, right?
If thats so, its a shame, but doesnt mean that much in this industry as far as i know?
Maybe we'll get some info next month? Any hints for that?
thanks

 

[trialAcc]

It's pretty much 1:1. I don't know where you got this idea that Androgenetic Alopecia is so different in macaques, but it's not supported by the literature. I already did the math in this post. We can estimate from the aforementioned study that finasteride increased terminal hair counts by up to 12.8/cm² in stumptailed macaques after 6 months versus 113/cm² for HMI-115. Per the following study finasteride increased hair counts in humans by 77 hairs in a 1 inch circle at 6 months. That's 15.1/cm², so slightly more than in the macaque study. Probably dead even because for this conversion I only calculated the maximum number of terminal hairs from the hair weight. It is likely a combination of terminal hairs and vellus hairs, which would likely mean finasteride increased terminal hair count in macaques by <10/cm², but increased total hair count by appx 15/cm², so pretty much exactly the same as in humans.

View attachment 174739

For an apples to apples comparison without any conversions, finasteride increased hair weight in humans by a net 25.6% compared to net 23% in macaques. It's not a guarantee, but based on the available evidence it is likely that HMI-115 will have approximately the same efficacy for Androgenetic Alopecia in humans that it does in macaques.

Do you happen to know how comparable the standard density of a macaques' hair for reference? 113 hairs per cm/sq is around 50-80% natural density for humans depending on the ethnicity and location on the scalp. I believe the average is about 170-200~ for all men.

 

[pegasus2]

Do you happen to know how comparable the standard density of a macaques' hair for reference? 113 hairs per cm/sq is around 50-80% natural density for humans depending on the ethnicity and location on the scalp. I believe the average is about 170-200~ for all men.

Rhesus macaques are around 360/cm on the forehead. In the Bayer study pre-treatment stumptailed macaques had 124 on the trunk. The patent states that trunk=back. Rhesus macaques have about 160 on the back, so about 29% more density than stumptailed macaques. That scale doesn't necessarily hold for the forehead. Also the sample size is small in both studies and varies significantly by individual monkey, so it's impossible to say with certainty based on the data I've seen. Human hair can be up to 400/cm on the crown. Average for Caucasians is one 200/cm and can be up to 400 on the crown, which is the densest part of the scalp before hair loss.

Macaques wound up with 216 thick hairs per cm on the bald area, so at least 50% density. 50% is the point where hair loss starts to become noticeable, so we should be able to get at least the appearance of a full head of hair.

 

[Ralph Wiggum]

The data is expected around the beginning of 2023, is that right?

 

[pegasus2]

comparing total scalp hair weight + hair length changes from finasteride against terminal hair count changes in isolated bald regions for HMI without even the smallest consideration of error when changing measures isn't even worth responding to

Is there something specific that you think I missed when doing the conversion, or are you just trolling? I assume you're trolling because you completely ignored the fact that I also provided a direct comparison of hair weights changes in macaques and humans which was statistically the same. There was no conversion needed for that, and thus no room for error, but keep cherry-picking

 

[pegasus2]

The data is expected around the beginning of 2023, is that right?

The trial hasn't started yet, but we would hope that we would have the data around that time if it starts soon.

 

[trialAcc]

Rhesus macaques are around 360/cm on the forehead. In the Bayer study pre-treatment stumptailed macaques had 124 on the trunk. The patent states that trunk=back. Rhesus macaques have about 160 on the back, so about 29% more density than stumptailed macaques. That scale doesn't necessarily hold for the forehead. Also the sample size is small in both studies and varies significantly by individual monkey, so it's impossible to say with certainty based on the data I've seen. Human hair can be up to 400/cm on the crown. Average for Caucasians is one 200/cm and can be up to 400 on the crown, which is the densest part of the scalp before hair loss.

Macaques wound up with 216 thick hairs per cm on the bald area, so at least 50% density. 50% is the point where hair loss starts to become noticeable, so we should be able to get at least the appearance of a full head of hair.

Right and this is 6 months. Is there any chance you think the actual usage will be a longer duration to achieve better results? If this treatment hypothetically ends up being able to restore roughly 50% natural density in 6 months, what's stopping the process from continuing though prolonged use?

 

[trialAcc]

well I'm curious to see what a more analytical approach might predict as a range of results than "it's 10x better than finasteride"

that whole post you reference was incredibly goofy and unscientific, arguing against the necessity of study controls or peer review

comparing total scalp hair weight + hair length changes from finasteride against terminal hair count changes in isolated bald regions for HMI without even the smallest consideration of error when changing measures isn't even worth responding to

in the end we'll find out when there's some actual human data (or not find out if it's abandoned)

Yup, the company that JUST got 56 million in venture capital funding with Androgenetic Alopecia listed as the primary target/first is going to abandon the indication. I'm sure they will also hand back the capital and admit defeat.

Dude you're a straight up troll. You just called a post that presented hard numbers goofy and unscientific yet none of your posts have anything but conjecture, playing devils advocate and fallaciously begging the question. The only reason it isn't worth responding to is because you're not actually intellectually capable of constructing a response so you just dismiss it entirely.

 

[FilthyFrancis]

Right and this is 6 months. Is there any chance you think the actual usage will be a longer duration to achieve better results? If this treatment hypothetically ends up being able to restore roughly 50% natural density in 6 months, what's stopping the process from continuing though prolonged use?

This remains unknown as of today.

 

[pegasus2]

Right and this is 6 months. Is there any chance you think the actual usage will be a longer duration to achieve better results? If this treatment hypothetically ends up being able to restore roughly 50% natural density in 6 months, what's stopping the process from continuing though prolonged use?

Perifollicular fibrosis. If fibrosis has progressed to the point that it has replaced the follicle then there is nothing left to regrow, although this happens very late in the process. Otherwise it would seem this turns off the mechanism that keeps hair follicles quiescent unlike minoxidil which only upregulates growth factors. That would suggest to me that it would over more time bring back every hair follicle in the scalp, as according to this study HF stem cells are retained in Androgenetic Alopecia. https://pubmed.ncbi.nlm.nih.gov/21206086/

That's the study which gave us hope that baldness could be reversed. I guess it just depends on how many stem cells are left in the individual hair follicle.

 

[-specter-]

Perifollicular fibrosis. If fibrosis has progressed to the point that it has replaced the follicle then there is nothing left to regrow, although this happens very late in the process. Otherwise it would seem this turns off the mechanism that keeps hair follicles quiescent unlike minoxidil which only upregulates growth factors. That would suggest to me that it would over more time bring back every hair follicle in the scalp, as according to this study HF stem cells are retained in Androgenetic Alopecia. https://pubmed.ncbi.nlm.nih.gov/21206086/

That's the study which gave us hope that baldness could be reversed. I guess it just depends on how many stem cells are left in the individual hair follicle.

couldn't stem cells be injected into the follicles that need them most?

 

[pegasus2]

couldn't stem cells be injected into the follicles that need them most?

If the follicle is not intact then what is required is what Tsuji or Stemson are doing which is much more complex.

 

[soull]

If the follicle is not intact then what is required is what Tsuji or Stemson are doing which is much more complex.

sorry partner if my translation is not correct to what I want to refer to according to what I have understood. Let's say that the follicle must maintain its cycle activity in order to benefit, right?

 

[pegasus2]

sorry partner if my translation is not correct to what I want to refer to according to what I have understood. Let's say that the follicle must maintain its cycle activity in order to benefit, right?

Yes

 

[trialAcc]

Perifollicular fibrosis. If fibrosis has progressed to the point that it has replaced the follicle then there is nothing left to regrow, although this happens very late in the process. Otherwise it would seem this turns off the mechanism that keeps hair follicles quiescent unlike minoxidil which only upregulates growth factors. That would suggest to me that it would over more time bring back every hair follicle in the scalp, as according to this study HF stem cells are retained in Androgenetic Alopecia. https://pubmed.ncbi.nlm.nih.gov/21206086/

That's the study which gave us hope that baldness could be reversed. I guess it just depends on how many stem cells are left in the individual hair follicle.

Considering it was only the two senile macaques that didn't respond in the study (and even at 5 months started to respond slightly), I would say it looks like the point of no return is very late in the process. The chart did not show signs of diminished returns at the point the study ended in males.

 

[pegasus2]

Considering it was only the two senile macaques that didn't respond in the study (and even at 5 months started to respond slightly), I would say it looks like the point of no return is very late in the process. The chart did not show signs of diminished returns at the point the study ended in males.

View attachment 174781

It's very promising. I'd love to see what those monkeys would look like after 12 months of treatment. Even one of the non-responders may have been starting to respond at week 24. It also may have been a seasonal fluctuation in anagen follicles

 

[Dimitri001]

And remember, even if some of the HFs are beyond recall, you can try to create new ones with microneedling.