Bayer Prolactin Receptor Antibody For Male And Female Pattern Hair Loss

[John Difool]

I am more inclined to think that she never considered hair loss as a market opportunity vs working for the greater goods as a women to treat breast cancer in other women. Not replying doesn't mean much beside that she didn't deny it as a scientific cancer research expert. We could speculate that she will try to investigate the hair loss path eventually (now she knows, thanks to you), although cancer seems a better mission that is keeping her and her team busy. Founding and grants may also be an issue in the hair loss research community. As for Bayer saying it doesn't work, it's also possible they meant it can work partially but wouldn't be replacement of HMI. I am still taking SMI oral at high dosage with the hope that it helps in dealing with high PR at the receptor level caused by higher E in my body (and why not for its main purpose too because of my blood serum level.) But I am not counting on it to be the cure. HMI on the other hand is much much more promising as a monotherapy while the jury is still out till we get results next year or so.

 

[Dimitri001]

You act like you're exposing some big secret, but I told people in the group buy thread that she said it doesn't work. Please at least be honest that I made people aware of everything that I knew, and made it clear that SMI might not work. Of course this researcher is trying to cure breast cancer not hair loss. She knows even less about hair loss than your local dermatologist, which isn't saying a whole lot, but I still wanted to point it out in the group buy. I also pointed out that the Bayer patent specifically states that competitive antagonists like SMI do not work. It's not like there was any harm in trying SMI. I do think it helped me some in the short time I was on it, but it is clearly not as efficacious as HMI-115, which was to be expected. View attachment 174378

By the way, the inventor of SMI stopped responding after she was shown Bayer's macaque study. If she thought it wouldn't translate to humans what was stopping her from replying with that?

Why did you decide to drop SMI?

 

[Otrebor]

For smi the game is not worth the candle (estimate anyway for those who have worked hard and tried it), has a low affinity and is a competitive inhibitor, I do not remember exactly the paper where it was mentioned but with inhibitors of this type yes potentially risks worsening the situation by increasing prolactin receptors. Probably by increasing the concentration and using it for more than 6 months you will be able to concretely observe a change. If there were more targeted and related prolactin inhibitors we might try them in the future.

Hmi also creates concerns for me, not so much related to the likelihood of it not working as to the multiple implications that prolactin has. A systemic elimination could have significant side effects in the long term (something that phase 1 studies cannot detect). Prolactin for example has implications for the preservation of pancreatic cells, it is really playing with fire.

But apart from this I have found interesting studies that I can relocate in my theory, as I have tried several times to say HMI is not only important in the direction of its therapeutic use, it can make us understand something more than baldness and perhaps make us discover more paths. simple to target locally with no side effects.

These two studies introduce a significant role of prolactin in the biology of the hair follicle (as well as for stem cells in general)

Minireview: Prolactin Regulation of Adult Stem Cells

Adult stem/progenitor cells are found in many tissues, where their primary role is to maintain homeostasis. Recent studies have evaluated the regulation of adult stem/progenitor cells by prolactin in various target tissues or cell types, including the ...

www.ncbi.nlm.nih.gov

Human scalp hair follicles are both a target and a source of prolactin, which serves as an autocrine and/or paracrine promoter of apoptosis-driven hair follicle regression - PubMed

The prototypic pituitary hormone prolactin (PRL) exerts a wide variety of bioregulatory effects in mammals and is also found in extrapituitary sites, including murine skin. Here, we show by reverse transcriptase-polymerase chain reaction and immunohistology that, contrary to a previous report...

pubmed.ncbi.nlm.nih.gov

These other two:

Prolactin and its receptor are expressed in murine hair follicle epithelium, show hair cycle-dependent expression, and induce catagen - PubMed

Here, we provide the first study of prolactin (PRL) and prolactin receptor (PRLR) expression during the nonseasonal murine hair cycle, which is, in contrast to sheep, comparable with the human scalp and report that both PRL and PRLR are stringently restricted to the hair follicle epithelium and...

pubmed.ncbi.nlm.nih.gov

Prolactin Signaling Influences the Timing Mechanism of the Hair Follicle: Analysis of Hair Growth Cycles in Prolactin Receptor Knockout Mice*

Abstract. Pituitary PRL regulates seasonal hair follicle growth cycles in many mammals. Here we present the first evidence implicating PRL in the nonseason

academic.oup.com

They clarify the issue even more at the cellular level. Prolactin can be a kind of "agent" put into standby of the stem cells of the follicle following the dead end that I hypothesized in the previous comments. Almost as if the prolactin came to calm the water following a stressful situation induced by the insanity of the cells and the dht, a situation that slowly however proceeds until the follicles are dead.

Prolactin is a vector, it is not a problem per se, probably HMI will work great (who knows) but given the importance that prl has in another myriad of paths I would not play with fire, especially if the fire will cost us 30k.

All that remains is to find the more specific pathways through which prolactin leads cells into apoptosis / quiescence.

Prolactin has implications with
- JAK / STAT
- BMP (specifically I think BMP4 ----> shh path)

and it certainly has some connection with androgens so I would not reject hypotheses related to a direct interaction.

Not giving any judgment before it is on the market HMI shows me however how in this industry most of the decisions are made: discovery of an element / drug / path that makes hair grow back ------> You do the tests without first yet to establish its complete functioning, thus contributing to total confusion in the pathogenesis of baldness.

Perhaps we should first of all get out of the idea that baldness is an exclusively aesthetic problem, not only because it has very evident psychological consequences but also for the fact that it is precisely starting from the development of a pathogenesis of such an intricate phenomenon that one can understand the mechanisms of a other myriad of pathologies, I have no inferiority complex for most of the companies that have tried to bring results in recent years, the empirical approach can be fine up to a certain point, after we need to deepen ...
but this is just my idea, and it doesn't apply to all scientists / entrepreneurs of course.

 

[-specter-]

What bothers me is the issue of baldness is not taken seriously, people take it for a joke. I think that there is no dignity in this, you can say what you want but get worse from the aesthetic point of view, not being able to manage your appearance as you want is not beautiful, being told that I have to make a reason for it and that I look like more man does not help me.

 

[coolio]

I'm always saying it. We would be out of this mess by now if researchers had been framing the problem differently for the past 30 years.

They should be talking about helping middle/older women with androgenic hair thinning. Nobody says "hair loss isn't a real problem" when it happens to women. And nobody doubts their willingness to pay money to look younger.

 

[Armando Jose]

I'm always saying it. We would be out of this mess by now if researchers had been framing the problem differently for the past 30 years.

I agree with you,..., and the key is front our nose, DHT is made inside pilosebaceous unit in scalp hairs years before puberty in all persons.

 

[Janko]

I agree with you,..., and the key is front our nose, DHT is made inside pilosebaceous unit in scalp hairs years before puberty in all persons.

Hola Armando,
You are true veteran here. I still remember you even from threads about seti etc. Btw. Since you have seen a lot of hypes here. What are you thoughts on Kintor and HMI?

 

[John Difool]

@Armando Jose has been on this site since Feb 2004. 17 years on a forum!

https://www.hairlosstalk.com/interact/threads/question-about-hair-transplants.3465/

 

[froggy7]

@Armando Jose has been on this site since Feb 2004. 17 years on a forum!

https://www.hairlosstalk.com/interact/threads/question-about-hair-transplants.3465/

dont worry John we all will be on this site in 2040, talking about pig trials round the corner

 

[Janko]

dont worry John we all will be on this site in 2040, talking about pig trials round the corner

The hairloss industry is fucked. I agree on this. But honestly I lurk here since 2014 and I see the situation improving. At that time there were only Replicel, Histogen and Follica. All were meme then and are complete meme now. New research was mostly based on arguments about prostaglandins, nofap, castor oil, every 3 months cetirizine being the cure etc. Getting some relatable news was pain in the ***.

Look at it now. We had several companies, that yes - failed, but after 3 decades we had company doing phase 3 study for hair loss. We now clearly see directions that did not work. Plenty of new companies and some of them moving quickly - Kintor as example. You can think what you want about folliclethought and hairlosscure2020, but their news are good. They bring interviews and have articles based on their knowledge of Androgenetic Alopecia not some stupid article from Jessica, that works for BBC claiming cure in 5 years etc. So it is easier for new people to get the news and it raises the stigma about hairloss - just shave it bro. Attention is what we need and companies now see people actually really care about hair.
I am not saying cure is behind the corner. But surely, things look more positive now than ever.

 

[Janko]

@Janko these were some the facts surrounding SMI, even if you take it for granted that HMI works exactly as described:

1. the antibody patent itself cites research that shows conventional PRLR antagonists are unlikely to work
2. prolactin is not well understood at all in men
3. the endocrine/autocrine/paracrine nature of even better understood hormones and hair cycling is still being probed
4. SMI cannot easily be dosed properly because it's never been tested on humans
5. the hair growth effect of the antibody in monkeys appears to have been a complete surprise (ie was not well-predicted by the current Androgenetic Alopecia model, even though it doesn't contradict it). This implies we don't understand the mechanism, making theoretical extensions difficult

but if you still decide to run the experiment, then at least an open discussion making it clear that it's a hail mary would limit the damage to people who are likely to get caught up in the hype

Hey, Fella,

You misunderstood me. I am not saying SMI works. I am just saying, that just because SMI does not work or at least on a paper, does not mean that HMI wont and that tackling the prolactin might be helpful for Androgenetic Alopecia. Since the beginning SMI was truly a hail mary. Pegasus also stated there. I was not part of the GB, but I value the people that went for it and tried it.
We understand sh*t about hairloss and the more angles they will try to resolve it, the better. I agree that the effect on macaques was a surprise. And that is not a reason to claim, that Prolactin direction is stupid and not based on scientific views. Minoxidil wasnt designed to be for hairloss neither finasteride. It was also a big surprise. There were plenty of new researchs, that reasoned nicely on paper and delivered nothing.

 

[froggy7]

Janko that is true, i agree 100% with You, but the case is that we wont be able to get our hir back in our best years

 

[John Difool]

Hey, Fella,

You misunderstood me. I am not saying SMI works. I am just saying, that just because SMI does not work or at least on a paper, does not mean that HMI wont and that tackling the prolactin might be helpful for Androgenetic Alopecia. Since the beginning SMI was truly a hail mary. Pegasus also stated there. I was not part of the GB, but I value the people that went for it and tried it.
We understand sh*t about hairloss and the more angles they will try to resolve it, the better. I agree that the effect on macaques was a surprise. And that is not a reason to claim, that Prolactin direction is stupid and not based on scientific views. Minoxidil wasnt designed to be for hairloss neither finasteride. It was also a big surprise. There were plenty of new researchs, that reasoned nicely on paper and delivered nothing.

Similar to minoxidil, finasteride was discovered by accident when it grew hair on the bald scalp in men treated for enlarged prostate.

Imagine if the scientists had overlooked that fleeting moment and didn't grab this opportunity? Great discoveries only come with serendipity, the knowledge to interpret things and the ability to grab the moment before it's too late.

 

[Dimitri001]

For smi the game is not worth the candle (estimate anyway for those who have worked hard and tried it), has a low affinity and is a competitive inhibitor, I do not remember exactly the paper where it was mentioned but with inhibitors of this type yes potentially risks worsening the situation by increasing prolactin receptors. Probably by increasing the concentration and using it for more than 6 months you will be able to concretely observe a change. If there were more targeted and related prolactin inhibitors we might try them in the future.

Hmi also creates concerns for me, not so much related to the likelihood of it not working as to the multiple implications that prolactin has. A systemic elimination could have significant side effects in the long term (something that phase 1 studies cannot detect). Prolactin for example has implications for the preservation of pancreatic cells, it is really playing with fire.

But apart from this I have found interesting studies that I can relocate in my theory, as I have tried several times to say HMI is not only important in the direction of its therapeutic use, it can make us understand something more than baldness and perhaps make us discover more paths. simple to target locally with no side effects.

These two studies introduce a significant role of prolactin in the biology of the hair follicle (as well as for stem cells in general)

Minireview: Prolactin Regulation of Adult Stem Cells

Adult stem/progenitor cells are found in many tissues, where their primary role is to maintain homeostasis. Recent studies have evaluated the regulation of adult stem/progenitor cells by prolactin in various target tissues or cell types, including the ...

www.ncbi.nlm.nih.gov

Human scalp hair follicles are both a target and a source of prolactin, which serves as an autocrine and/or paracrine promoter of apoptosis-driven hair follicle regression - PubMed

The prototypic pituitary hormone prolactin (PRL) exerts a wide variety of bioregulatory effects in mammals and is also found in extrapituitary sites, including murine skin. Here, we show by reverse transcriptase-polymerase chain reaction and immunohistology that, contrary to a previous report...

pubmed.ncbi.nlm.nih.gov

These other two:

Prolactin and its receptor are expressed in murine hair follicle epithelium, show hair cycle-dependent expression, and induce catagen - PubMed

Here, we provide the first study of prolactin (PRL) and prolactin receptor (PRLR) expression during the nonseasonal murine hair cycle, which is, in contrast to sheep, comparable with the human scalp and report that both PRL and PRLR are stringently restricted to the hair follicle epithelium and...

pubmed.ncbi.nlm.nih.gov

Prolactin Signaling Influences the Timing Mechanism of the Hair Follicle: Analysis of Hair Growth Cycles in Prolactin Receptor Knockout Mice*

Abstract. Pituitary PRL regulates seasonal hair follicle growth cycles in many mammals. Here we present the first evidence implicating PRL in the nonseason

academic.oup.com

They clarify the issue even more at the cellular level. Prolactin can be a kind of "agent" put into standby of the stem cells of the follicle following the dead end that I hypothesized in the previous comments. Almost as if the prolactin came to calm the water following a stressful situation induced by the insanity of the cells and the dht, a situation that slowly however proceeds until the follicles are dead.

Prolactin is a vector, it is not a problem per se, probably HMI will work great (who knows) but given the importance that prl has in another myriad of paths I would not play with fire, especially if the fire will cost us 30k.

All that remains is to find the more specific pathways through which prolactin leads cells into apoptosis / quiescence.

Prolactin has implications with
- JAK / STAT
- BMP (specifically I think BMP4 ----> shh path)

and it certainly has some connection with androgens so I would not reject hypotheses related to a direct interaction.

Not giving any judgment before it is on the market HMI shows me however how in this industry most of the decisions are made: discovery of an element / drug / path that makes hair grow back ------> You do the tests without first yet to establish its complete functioning, thus contributing to total confusion in the pathogenesis of baldness.

Perhaps we should first of all get out of the idea that baldness is an exclusively aesthetic problem, not only because it has very evident psychological consequences but also for the fact that it is precisely starting from the development of a pathogenesis of such an intricate phenomenon that one can understand the mechanisms of a other myriad of pathologies, I have no inferiority complex for most of the companies that have tried to bring results in recent years, the empirical approach can be fine up to a certain point, after we need to deepen ...
but this is just my idea, and it doesn't apply to all scientists / entrepreneurs of course.

The fact that it has a lower affinity than PRL doesn't mean it can't work. CB and RU have lower affinities than DHT and even T, yet they work. Imagine if SMI also works - it could potentially give you HMI results.

 

[badnewsbearer]

Similar to minoxidil, finasteride was discovered by accident when it grew hair on the bald scalp in men treated for enlarged prostate.

Imagine if the scientists had overlooked that fleeting moment and didn't grab this opportunity? Great discoveries only come with serendipity, the knowledge to interpret things and the ability to grab the moment before it's too late.

it was not discovered by accident, there was an expedition of a team of researchers to an ubundant south pazifik(?) island years prior and they discovered a native stem of people that had 5AR deficiencies/mutations so their bodies could not produce DHT. noneof them had hair loss. that is when they realized that inhibition or dysfunction of 5AR enzyme plays a key role in androgenic alopecia. this was then broight to the attention of merck who was already working on a 5ARi for prostate enlargement. then they decided to trial it for another condition. so to say they were shell shocked that some people regrew haie is not sccurate i think. with minoxidil however it is. crazy that just by chance there has not been a similar accidential finding since then, truly unfortunate

 

[badnewsbearer]

The fact that it has a lower affinity than PRL doesn't mean it can't work. CB and RU have lower affinities than DHT and even T, yet they work. Imagine if SMI also works - it could potentially give you HMI results.

but CB does not work becsuse it has such a low affinity right? RU may work i do not know there is no study on it

 

[pegasus2]

Crazy that just by chance there has not been a similar accidential finding since then, truly unfortunate

There has, just ask Bayer and HMI. Imagine hmmm in 1980s "Guys, minoxidil is a blood pressure drug. The science says it won't work, Androgenetic Alopecia is caused by dht and lack of brocolli in your diet, it has nothing to do with blood pressure. Stop trying things that aren't backed by science"

 

[badnewsbearer]

There has, just ask Bayer and HMI. Imagine hmmm in 1980s "Guys, minoxidil is a blood pressure drug. The science says it won't work, Androgenetic Alopecia is caused by dht and lack of brocolli in your diet, it has nothing to do with blood pressure. Stop trying things that aren't backed by science"

minoxidl progress declines pretty damn fast after discontinuation. what is the mechanism that virtually protects the macaques hairs after the treatment period for 2 years on? and if that does not translate, how much is this animal model really worth? it is not that hmi can regrow hair, it is how it does it and hoe long it lasts that is exciting and that cannot be explained. i am quite suprised they did not take scalp biopsies from the macaques at this opportunity, wfter all this model is rarely used to due cost and riak handling such animals, they coule have tried to find out the molecular underpinnings of these "cured" hair follicles and gave this all much more credibility. however it can still be solid, it just is nog clear what mechanism could get activated for the effect to endure for so long.

 

[Chads don't bald]

What do you guys think about Hairclone? Its supposed to be out in 2022 I think and it's an upgrade over replicel? Any hope?

 

[froggy7]

my only option is Stemson