HMI-115 PRLR antibody: The Most Promising Treatment Ever

[Hairful]

No offense, but you sound like a hypochondriac and a pessimist. The only concern I have is if the drug works in humans. We could have some redundant pathway the monkeys don't have which will keep HFSCs quiescent even without PRLRs. This seems unlikely, but much more likely than PRLR antagonism being life threatening. Male mice without prolactin receptors live normal lives.

Not really, we already know several pathways that hairloss can be stopped but we can’t inhibit or enhance those pathways due to obvious side effects on the whole body. That’s the challenge with fighting hairloss. E.g the wnt pathway, the TGF-β1 suppressed by Botox and DHT through finasteride.

Prolactin isn’t a hormone like DHT, it’s involved in immune system and other important biological functions. Unlike DHT which is mainly sexual and it’s involved in causing diseases after a certain age (prostate)

So yeah, I am cautious and not really getting my hopes up until they can prove it’s safety in large trials

 

[HMI 115 IS THE CURE dude]

Here's a rat study showing Prolactin is involved in preservation of 5AR enzyme in testis.

Prolactin involvement in regulation of testicular 5 alpha-reductase activity in the immature rat - PubMed

Treatment of intact immature (25-day-old) rats with bromoergocryptine (BR), which suppressed prolactin (Prl) secretion, decreased testicular 5 alpha-reductase activity, whereas treatment with Prl increased the enzyme activity in BR-treated animals. Serum luteinizing hormone (LH) concentrations...

pubmed.ncbi.nlm.nih.gov

Looks like without Prolactin signaling, 5AR enzyme might degrade much more quickly, at least in rat testicles. Perhaps it is similar in hair follicles, 5AR levels are mediated not by Testosterone but by Prolactin.

Edit: This study is from 1985 which is horrifying, the association between Prolactin and 5AR has been known about for 40 years and just now are we coming around to the idea that it might be a big player in Androgenetic Alopecia....

Awesome find man. Imagine how powerful hmi + an anti androgen will be at silencing 5ar activity

 

[pegasus2]

Not really, we already know several pathways that hairloss can be stopped but we can’t inhibit or enhance those pathways due to obvious side effects on the whole body. That’s the challenge with fighting hairloss. E.g the wnt pathway, the TGF-β1 suppressed by Botox and DHT through finasteride.

Prolactin isn’t a hormone like DHT, it’s involved in immune system and other important biological functions. Unlike DHT which is mainly sexual and it’s involved in causing diseases after a certain age (prostate)

So yeah, I am cautious and not really getting my hopes up until they can prove it’s safety in large trials

We don't have drugs capable of targeting the Wnt pathway in the HF. It's not that simple. There is the possibility that using a cocktail of drugs including a direct Fzd agonist would reverse Androgenetic Alopecia, but yes that could very well cause cancer too. There's good reason to believe based on mouse and cancer studies that this is a legitimate concern. All evidence shows that prolactin is only a modulator and not a master regulator of immune function, and that we don't need it. Unless you have links to studies showing otherwise then you're only spreading paranoia. Mice that live their whole lives with the PRLR completely removed are healthy and live the same amount of time as control mice. The only difference is that they have slight bone loss, the females can't lactate and are infertile(reversible), and that they have less abdominal fat, and non-cancerous pituitary growth.

 

[Feelsbadman.jpg]

Awesome find man. Imagine how powerful hmi + an anti androgen will be at silencing 5ar activity

Yes I think(hope) at the very least HMI 115 will make 5AR inhibitors 100% effective in that any and all hair that can be recovered will be (as long as there is no scar tissue). My thinking on this is based on babies/new borns. 5AR and DHT are very high in male babies (in fact, I believe DHT levels are highest in the womb out of any other point in life) and you may have noticed, they look like they are balding when born. However, all kids grow juvenile hairlines. I think this is because, as the study below shows, 5AR levels drop to nothing after 1.5 years in the scalp. Even dutasteride at 2.5 mg ED doesn't eliminate 100% of 5AR. If Prolactin receptor stimulation is increasing 5AR production and causing it stick around longer, then silencing it should make 5AR inhibitors much more effective.

The 5 Alpha-Reductase Isozyme Family: A Review of Basic Biology and Their Role in Human Diseases

Despite the discovery of 5 alpha-reduction as an enzymatic step in steroid metabolism in 1951, and the discovery that dihydrotestosterone is more potent than testosterone in 1968, the significance of 5 alpha-reduced steroids in human diseases was not ...

www.ncbi.nlm.nih.gov

Newborn-Onset of Puberty In newborns, 5α-R1 is expressed at the protein level in the liver, skin, scalp [13] and prostate [55]. 5α-R2 is expressed in prostate, seminal vesicles, epididymis, liver, and to lesser extent in scalp and skin [13]. Hepatic expression of 5α-R1 and 2 is present at the protein level (immunoblotting) throughout postnatal life. At approximately 1.5 years, the expression of both proteins is not detected in the skin and scalp until the onset of puberty.

 

[pegasus2]

This seems coherent with our broscience theories that PRL might be involved in regulating the sensitivity of follicles to androgens. It would mean that the real cause of Androgenetic Alopecia has been found pretty much. But it is still very surprising that this can't be reproduced in any other way than HMI-115 even in vitro follicles... thats the part that makes me a bit skeptical still.

Not only that, prolactin upregulates Twist1 which induces aberrant AR activation that can't be overcome by castration or enzalutamide.

 

[hairlossisevil]

If this pathway actually works, surely a topical alternative that ultimately does the same thing could be developed and be cheaper, right? I mean I understand this is a subcutaneous injection because it's primary goal is treatment of endo. male pattern baldness was basically an afterthought.

 

[coolio]

Not only that, prolactin upregulates Twist1 which induces aberrant AR activation that can't be overcome by castration or enzalutamide.

That would help explain some of the difficulty with reversing the balding process via androgen drugs.

 

[pegasus2]

If this pathway actually works, surely a topical alternative that ultimately does the same thing could be developed and be cheaper, right? I mean I understand this is a subcutaneous injection because it's primary goal is treatment of endo. male pattern baldness was basically an afterthought.

It may not be possible. To reverse hair loss it might be necessary to block the PRLR systemically.

Hair follicles chemotactically attract macrophages and T cells so that they are in range to regulate epithelial stem cell quiescence, proliferation and differentiation during physiologic and injured states. Disruption of this dynamic relationship leads to clinically significant forms of hair loss including scarring and non-scarring alopecias.

Immune modulation of hair follicle regeneration - npj Regenerative Medicine

The mammalian hair follicle undergoes repeated bouts of regeneration orchestrated by a variety of hair follicle stem cells. The last decade has witnessed the emergence of the immune niche as a key regulator of stem cell behavior and hair follicle regeneration. Hair follicles chemotactically...

www.nature.com

If it is not necessary to block PRLR signaling in macrophages too then it is possible to apply it to the scalp only using mesotherapy, or that another drug could be developed which could be applied topically, but that's unlikely to happen anytime soon and nothing is safer than an antibody. Small molecule drugs have off-target effects, and other problems that make them less safe and less effective. Antibodies are too large to penetrate the skin, but they are highly specific. This drug only affects the PRLR and nothing else.

As for what this drug was created for, I doubt they had a specific disease in mind. Most likely they thought it would be a valuable drug for various cancers and autoimmune disorders. There was no effective drug for targeting the PRLR despite its suspected importance in many diseases, so they created one and sold it to Bayer. If it was so easy to create a small molecule drug that can do the same thing then they would have. SMI-6 is being developed for that purpose for treating breast cancer, but it was tried by forum members and didn't seem to work very well. Antibodies are just vastly superior to small molecules that can be applied topically. I don't think people should get their hopes up for an alternative to this, certainly not a safer or cheaper one. That probably won't exist.

 

[pegasus2]

Yes I think(hope) at the very least HMI 115 will make 5AR inhibitors 100% effective in that any and all hair that can be recovered will be (as long as there is no scar tissue). My thinking on this is based on babies/new borns. 5AR and DHT are very high in male babies (in fact, I believe DHT levels are highest in the womb out of any other point in life) and you may have noticed, they look like they are balding when born. However, all kids grow juvenile hairlines. I think this is because, as the study below shows, 5AR levels drop to nothing after 1.5 years in the scalp. Even dutasteride at 2.5 mg ED doesn't eliminate 100% of 5AR. If Prolactin receptor stimulation is increasing 5AR production and causing it stick around longer, then silencing it should make 5AR inhibitors much more effective.

The 5 Alpha-Reductase Isozyme Family: A Review of Basic Biology and Their Role in Human Diseases

Despite the discovery of 5 alpha-reduction as an enzymatic step in steroid metabolism in 1951, and the discovery that dihydrotestosterone is more potent than testosterone in 1968, the significance of 5 alpha-reduced steroids in human diseases was not ...

www.ncbi.nlm.nih.gov

I doubt this has much to do with the moa of HMI-115. Enzalutamide blocks the AR nearly 100%, effectively eliminating DHT, yet it does not grow much hair. Men who are castrated also do not regrow their hair. We can infer from these observations that simply eliminating 5-ar2 is not enough to reverse hair loss.

 

[Feramon1]

I doubt this has much to do with the moa of HMI-115. Enzalutamide blocks the AR nearly 100%, effectively eliminating DHT, yet it does not grow much hair. Men who are castrated also do not regrow their hair. We can infer from these observations that simply eliminating 5-ar2 is not enough to reverse hair loss.

Then what does estrogen have to do with it and how does HRT affect prolactin? Obviously, HRT gives new hair growth, and if you take women, then their prolactin is on average higher than that of men, at least in serum. Although I assume that the number may not matter.

 

[pegasus2]

Then what does estrogen have to do with it and how does HRT affect prolactin? Obviously, HRT gives new hair growth, and if you take women, then their prolactin is on average higher than that of men, at least in serum. Although I assume that the number may not matter.

Correct, serum prolactin is irrelevant. It's been demonstrated to have no effect on the HF. ePRL such as found in the skin, HF, and macrophages is regulated independently of serum prolactin, which is regulated by dopamine through the pituitary gland. The answer to the other part is no one knows. Part of it is by regulating anti-apoptotic genes like BCL2.

 

[Feelsbadman.jpg]

I doubt this has much to do with the moa of HMI-115. Enzalutamide blocks the AR nearly 100%, effectively eliminating DHT, yet it does not grow much hair. Men who are castrated also do not regrow their hair. We can infer from these observations that simply eliminating 5-ar2 is not enough to reverse hair loss.

But it is enough to prevent it from ever occurring for life in those who never have it. I'm just hypothesizing that the reason Finasteride stops working for some people after many years might be due to increasing amounts of 5AR being produced that degrades slower and prolactin might be involved. Also, babies born with "receding hairlines" grow their hairlines in an environment with no scalp 5AR. So it seems eliminating 5AR is a prerequisite to reverse hairloss but not all that is required.

 

[Feelsbadman.jpg]

It may not be possible. To reverse hair loss it might be necessary to block the PRLR systemically.

Immune modulation of hair follicle regeneration - npj Regenerative Medicine

The mammalian hair follicle undergoes repeated bouts of regeneration orchestrated by a variety of hair follicle stem cells. The last decade has witnessed the emergence of the immune niche as a key regulator of stem cell behavior and hair follicle regeneration. Hair follicles chemotactically...

www.nature.com

If it is not necessary to block PRLR signaling in macrophages too then it is possible to apply it to the scalp only using mesotherapy, or that another drug could be developed which could be applied topically, but that's unlikely to happen anytime soon and nothing is safer than an antibody. Small molecule drugs have off-target effects, and other problems that make them less safe and less effective. Antibodies are too large to penetrate the skin, but they are highly specific. This drug only affects the PRLR and nothing else.

As for what this drug was created for, I doubt they had a specific disease in mind. Most likely they thought it would be a valuable drug for various cancers and autoimmune disorders. There was no effective drug for targeting the PRLR despite its suspected importance in many diseases, so they created one and sold it to Bayer. If it was so easy to create a small molecule drug that can do the same thing then they would have. SMI-6 is being developed for that purpose for treating breast cancer, but it was tried by forum members and didn't seem to work very well. Antibodies are just vastly superior to small molecules that can be applied topically. I don't think people should get their hopes up for an alternative to this, certainly not a safer or cheaper one. That probably won't exist.

I was searching for a study on the effects of exercise and PRLR and unfortunately found this.

Exercise increases prolactin-receptor expression on human lymphocytes | Journal of Applied Physiology

Plasma prolactin has been shown to increase during stress; the immune system is responsive to prolactin and affected by stress. Therefore, this study was undertaken to investigate the effects of acute graded, maximal treadmill exercise on prolactin-receptor expression by lymphocytes. Eight...

journals.physiology.org

Plasma prolactin concentrations were significantly elevated in response to exercise and correlated positively with total prolactin-receptor expression per B lymphocyte. An increase in total prolactin-receptor expression per B lymphocyte in response to exercise also was observed. In addition, exercise significantly increased the total number of circulating B lymphocytes expressing prolactin receptor as well as the total number of circulating B lymphocytes.

B Lymphocytes are not the same as macrophages but likely the same thing occurs as the following references the alleged immune enhancing properties of prolactin of which, macrophages are mentioned (Phagocytosis is beneficial).

For instance, prolactin can enhance antibody production, lymphocyte proliferation, natural killer (NK) cell activity, and macrophage phagocytosis (7, 31, 38). It also may be important in immune cell development (8).

Maybe the anecdotes of exercise making hair loss worse is not just from the increased T but from increased PRLR expression on macrophages?Exercise enhances immune system and this would benefit mammalian hair follicles in the prevention of alopecias but human scalp hair does not behave like typical mammalian hair follicles(scalp hair growth has inverse relationship with DHT) so it could contribute to the Androgenetic Alopecia process more efficiently? I hope this is wrong.

 

[pegasus2]

I was searching for a study on the effects of exercise and PRLR and unfortunately found this.

Exercise increases prolactin-receptor expression on human lymphocytes | Journal of Applied Physiology

Plasma prolactin has been shown to increase during stress; the immune system is responsive to prolactin and affected by stress. Therefore, this study was undertaken to investigate the effects of acute graded, maximal treadmill exercise on prolactin-receptor expression by lymphocytes. Eight...

journals.physiology.org

B Lymphocytes are not the same as macrophages but likely the same thing occurs as the following references the alleged immune enhancing properties of prolactin of which, macrophages are mentioned (Phagocytosis is beneficial).


Maybe the anecdotes of exercise making hair loss worse is not just from the increased T but from increased PRLR expression on macrophages?Exercise enhances immune system and this would benefit mammalian hair follicles in the prevention of alopecias but human scalp hair does not behave like typical mammalian hair follicles(scalp hair growth has inverse relationship with DHT) so it could contribute to the Androgenetic Alopecia process more efficiently? I hope this is wrong.

Exercise also induces oxidative stress which increases the binding affinity of prolactin. However, moderate exercise reduces oxidative stress at rest, so as long as you give your body enough rest it is probably beneficial in this regard.

 

[Dogchebag]

I didn't like reading this thread as I'm gonna start the gym full and currently I had nearly perfect hair for the past 4 months.

 

[Feelsbadman.jpg]

I didn't like reading this thread as I'm gonna start the gym full and currently I had nearly perfect hair for the past 4 months.

I would not stop working out just because of some speculation on my part. It's probably wrong. I just got done lifting weights and running and don't plan on stopping. If you are on a 5AR inhibitor, any negative impact exercise could potentially have on hair should be negligible. And like Pegasus mentioned the benefits probably outweigh the negatives even from a hair perspective. Exercise increases insulin sensitivity which increases SHBG which should increase total T reduce free T available for conversion by 5AR. Plus countless other benefits for overall health and longevity.

 

[pegasus2]

I didn't like reading this thread as I'm gonna start the gym full and currently I had nearly perfect hair for the past 4 months.

Don't worry about it. I highly doubt it makes a significant difference if at all. Working out is probably a net benefit to hair unless you do steroids

 

[Feramon1]

I already wrote something similar in other topics, but I repeat, maybe someone will be interested. For the past 3 years, I have been very closely monitoring the reaction of my hair and the actions that affect it. My baldness is characterized by itching and "goosebumps", I have an instant reaction if I do something that affects them. For all the time, from the moment I started to go bald, the absolute relationship, I emphasize "absolute", has:

1. Sex, masturbation, arousal
2. Stress (I will even tell you what emotions - resentment, nervousness, frustration and shock)
3. Heavy sports (no steroids, only weights)

My case helps me to determine this, since these actions are accompanied by a reaction in the form of itching and hair loss, but I believe that many do not have itching and baldness is asymptomatic and I assume that they simply do not notice it. I have checked this many times, in this respect I am absolutely sure of what I am talking about.

I will add one more thing here, my hair literally transforms, it can become thinner or thicker and more voluminous in a day. After sex (ejaculation), the hair looks better for a few hours, then becomes thinner and worse. I linked this to oxytocin, but I couldn't find a single sane study stating its connection to hair. It is quite difficult for me to read studies or look for them in a non-native language, perhaps this is the problem.Based on the above, I can assume that prolactin in the follicles rises along with serum, but I'm not sure about the decrease.

I also think I'm the perfect test subject because I don't have to wait months for results, I know almost immediately what works and what doesn't. So if you have something to offer and it doesn't kill me, go for it.

 

[genericwhitemale]

I already wrote something similar in other topics, but I will repeat maybe someone will find it interesting. I have been very closely monitoring the reaction of my hair and the actions that affect it for the past 3 years. My baldness is characterized by itching and "pins and needles", I have an instant reaction if I do something that affects them. For all the time, from the moment I started to go bald, the absolute relationship, I emphasize "absolute" has:

1. Sex, masturbation, arousal
2. Stress (I will even tell you what emotions - resentment, nervousness, frustration and shock)
3. Heavy sports (no steroids, just weights)

My case helps me determine this, since these actions are accompanied by a reaction in the form of itching and hair loss, but I believe that many do not have itching and baldness is asymptomatic and I assume that they simply do not notice it. I have rechecked this many times, in this respect I am absolutely sure of what I am talking about.

I will add one more thing here, my hair is literally changing, it can become thinner or thicker and more voluminous in a day. After sex (ejaculation), the hair looks better for a few hours, then it becomes thinner and worse. I associated this with oxytocin, but I did not find a single sane study that would talk about its connection with hair. It is quite difficult for me to read studies or look for them in a non-native language, this may be the problem.
Based on what I wrote above, I can assume that prolactin in the follicles rises along with serum, but not sure about lowering.

I also think that I'm the perfect test subject because I don't have to wait months for results, I'll know almost immediately what works and what doesn't. So if you have something to offer and it won't kill me, go for it

Biggest load of nonsense I have ever read.

Your hair doesn't get thinner after a few hours post-ejaculation you maniac. Imagine actually thinking that your follicles reacted instantly to a treatment or situation.

Stop spreading misinformation.

 

[HMI 115 IS THE CURE dude]

Biggest load of nonsense I have ever read.

Your hair doesn't get thinner after a few hours post-ejaculation you maniac. Imagine actually thinking that your follicles reacted instantly to a treatment or situation.

Stop spreading misinformation.

i agree . Personally I think alot of guys say this due to a rapid psychological change that happens pre and post ejaculation. You go from uber confident with yourself and body/hair/looks to being more critical and reserved.