Effect of HMI-115 was discovered by accident in a similar manner as Finasteride. Was being used to treat endometriosis, when Bayer noticed mice regrew hair.
Bayer was not interested in researching HMI-115's potential effects on AGA, as they had pivoted towards women's issues. However, Rui-Ping Xiao, who was working with them, asked to test the drug on bald, stumptailed macaques. This is where we get the pictures showing hair growth through four years. Bayer agreed, and when the results came in she formed HopeMed Inc., and purchased the global rights to the drug from Bayer in 2019.
The bald, stumptailed macaques are unique in hair-loss research in that they experience AGA in the same way humans do. DHT causes their follicles to miniaturize, and they go bald in a similar pattern as us. Previous hair-loss treatments such as Finasteride and minoxidil show similar efficacies in macaques as they do in us. Hair transplants work for them, just like for us.
To clear up some confusion regarding results on the macaques: The observation period is still ongoing. The macaques did not lose all their hair after four years. Furthermore, slight regression was experienced after cessation of the 6-month treatment in some of the macaques. However, that slight regression stabilized soon after cessation, and the macaques experienced regrowth far after cessation of treatment. Again, the observation period is still ongoing. The macaques have kept their hair for four years and counting.
14 genes were found upregulated in frontal vs vertex scalp. At least 10 of them are upregulated by prolactin receptor signaling, and 2 others induce prolactin secretion. Many of these genes are also upregulated by Wnt inhibition.
Prolactin receptor in follicles may play a role in alopecia areata.
DHT induces increased prolactin production. DHT doesn't directly cause miniaturization; DHT binding to follicles increases prolactin, which in turn causes miniaturiaztion. DHTs role in hair loss is finally adequately explained.
The role of prolactin in hair loss has been known for two decades now. No research has been done because no one bothered to develop a prolactin receptor antagonist.
At least in certain blood cells PRLR expression increases in adulthood as GHR expression decreases. This coincides with the time when men start losing their hair. Additionally, newborns have extremely high levels of serum prolactin, 100-300ng/ml, well beyond hyperprolactinema levels of 20ng/ml. This could be why newborns lose hair in the male pattern baldness pattern, and lends some credibility to the theory that PRLR expression is responsible for the hair loss pattern found in Androgenetic Alopecia. Prolactin levels return to normal in the weeks to months before babies regrow their hair.