@pegasus2 is approaching his late 70s though
I'll be dead before it's available
If it works and if it's out before we're in old folks' homes and if it's in our price range.
Decades
Tbh aging itself will probably be under control by 2050 ish, so if you can survive till 2050 you can survive much longer (longevity escape velocity)
www.ncbi.nlm.nih.gov
academic.oup.com
www.ncbi.nlm.nih.gov
www.researchgate.net
www.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
Their goal was to start trials in multiple indications in 2021:After the last communication of HopeMedicine (19th ocotober 2021 产业基地启航！北大分子医学南京转化研究院产业发展基地正式启用 - 园区要闻 - 南京生物医药谷 (njbpv.cn)):
"Heqirui is an innovative biopharmaceutical company based on Professor Xiao Ruiping and his team from the School of Future Technology of Peking University, based on decades of research results in the field of translational medicine. At present, the company has completed the B round of financing, and signed a global exclusive license agreement with Bayer for the development and industrialization of the monoclonal antibody HMI-115 targeting the prolactin receptor (PRLR), and is developing and industrializing multiple indications worldwide change. This antibody has the function of promoting hair growth and has a therapeutic effect on hair loss. It has shown excellent characteristics in animal models and human safety, and has obtained the approval of the US FDA Phase II clinical trial. The US Phase II clinical trial will be launched in the near future. The patient is enrolled. In addition, Heqirui has also carried out the R&D and industrialization of more high-end innovative drugs through the dual-drive model of license-in (authorized introduction) and independent research and development."
i am now thinking that they wanted to tell us that the antibody has the potential to grow hair. But that the US Phase II clinical trial will be launched was only connected to the treatment of endometriosis i think. That is why they started the trial for Endometriosis in November. It isnt said that the hairloss trial would start also in the near future. They told only that THE US Phase II clinical trial (that means only 1 trial, NOT multiple clinical trials like they said in 2020) will be launched in the near future which has now been done with the endometriosis trial.
It seems like their goal only was to start a clinical trial with this monoclonal antibody HMI-115 which they have done now. It could now be a long time until the start trials for another conditions (hair loss)
en.prnasia.com
Their goal was to start trials in multiple indications in 2021:
Hope Medicine Inc. Announced Dr. Henri Nico Doods as President and Head of Research & Clinical Development - PR Newswire APAC
SHANGHAI, Dec. 14, 2020 /PRNewswire/ -- Hope Medicine Inc. Announced Dr. Henri Nico Doods as President and Head of Research & Clinical Development
"HMI-115, a prolactin receptor antibody, has passed animal experiments and phase I clinical human studies, and will enter phase II trials in multiple indications in 2021."
In this interview it was also mentioned that they want to start in Summer 2021:
和其瑞医药联合创始人肖瑞平：医药强国，吾辈使命 - 创新人才 - 南京生物医药谷
· 和其瑞医药有限公司联合创始人、董事长兼首席执行官；· 北京大学讲席教授，北大分子医学研究所所长；· 《新英格兰医学期刊》副主编www.njbpv.cn
They have removed the information though, so they probably are just delayed.
If only we could identify something downstream of PRLR activation that we could somehow target more cheaply and right now, without having to wait for HMI, which, who knows when it will become commercially available and whether it will be affordable.Acetylation modulates prolactin receptor dimerization
Prolactin receptors: New mechanism may play role in cancer
If women had no prolactin receptors on cells in their mammary glands, they would not produce milk when they were nursing. Prolactin receptors are also found in other organs including the lung and the colon. The only problem is that these receptors are sort of like cellular wiring, and when the...www.sciencedaily.com
HDAC4/9 are present in healthy hair follicles and this study reveals they are strongly associated with Androgenetic Alopecia. It was always assumed that this association was due to them being corepressors of the AR, but they are also corepressors of the PRLR.
I think the balance of HDACs and HATs is skewed in Androgenetic Alopecia creating upregulation of AR and PRLR, which ultimately represses canonical Wnt signaling, causing a progressively shorter anagen phase. From the top SNPs in this study there is the AR of course, then genes that regulate AR and PRLR transactivation, PAX1 and TWIST which are involved in Wnt signaling and upregulated by PRLR. It certainly seems like Androgenetic Alopecia is driven by coactivation of the AR and PRLR. AR activation itself recruits histone acetyltransferases, which upregulate PRLR. Crosstalk between the two then takes place.
ASC-J9 may be an ideal AR antagonist to use with HMI-115, as curcumin inhibits HATs.
HAT inhibitors have shown success in prostate cancer.
"A limited number of HAT inhibitors are in preclinical or clinical trials, with p300/CBP and P/CAF-specific inhibitors showing the most promising effects"
Androgen Receptor Signalling in Prostate Cancer: The Functional Consequences of Acetylation
The androgen receptor (AR) is a ligand activated transcription factor and member of the steroid hormone receptor (SHR) subfamily of nuclear receptors. In the early stages of prostate carcinogenesis, tumour growth is dependent on androgens, and AR directly ...
This CREB binding protein inhibitor may be effective against Androgenetic Alopecia by inhibiting both AR and PRLR transactivation
Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours - Nature
A potent and selective catalytic inhibitor of p300/CBP histone acetyltransferases suppresses tumour proliferation across multiple cell lineages, illustrating the therapeutic potential of drug-like small molecules that target histone acetyltransferases.www.nature.com
Estradiol promotes prolactin transactivation by inducing histone acetylation through ERα, but the predominant estrogen receptor in the scalp is ERβ and it silences ERα. So estradiol does not upregulate prolactin signaling in the hair follicle, despite upregulating it in other tissues.
Epigenetic Mechanisms in the Dopamine D2 Receptor-Dependent Inhibition of the Prolactin Gene
Abstract. Transcription of the prolactin gene is dynamically controlled by positive and negative hormone signals that target the regulatory promoter region. Bas
HDAC inhibitors also work for prostate cancer, through inhibiting HSP90.
Androgen Receptor Signalling in Prostate Cancer: The Functional Consequences of Acetylation
The androgen receptor (AR) is a ligand activated transcription factor and member of the steroid hormone receptor (SHR) subfamily of nuclear receptors. In the early stages of prostate carcinogenesis, tumour growth is dependent on androgens, and AR directly ...
Prolactin actually upregulates HSP90
ATM Is Required for the Prolactin-Induced HSP90-Mediated Increase in Cellular Viability and Clonogenic Growth After DNA Damage | Request PDF
Request PDF | ATM Is Required for the Prolactin-Induced HSP90-Mediated Increase in Cellular Viability and Clonogenic Growth After DNA Damage | Prolactin acts as a survival factor for breast cancer cells, but the prolactin signaling pathway and the mechanism is unknown. Previously, we... | Find...
It is theorized that in castration resistant prostate cancer AR activation is continued in part by "mechanisms including activation of kinase pathways that can both stabilize AR and enhance its transcriptional activity and upregulations of AR coactivators that increase AR mediated transcription. These sensitize AR to lower levels of ligand."
Targeting the androgen receptor pathway in prostate cancer
When prostate cancers progress following androgen depletion therapy, there are currently few treatment options with only one, docetaxel, that has been shown to prolong life. Recent work has shown that castration resistant prostate cancers (CRPC) continue ...
Prolactin upregulates all of these pathways that hypersensitize the AR.
You can see from all this that the AR and PRLR are very interconnected. It's not hard to imagine that silencing the PRLR would stop the positive feedback loop between the two receptors and reverse male pattern baldness in a more potent and lasting way than current treatments, which is what was observed in stump-tailed macaques. Returning AR sensitivity to normal and restoring homeostasis could give lasting results that simple DHT inhibition does not.
Ultimate hair loss stack?: HMI-115, ASC-J9, Estriol. Nothing else needed for full reversal?
I understand the Discord guys inquired about it with labs and were quoted an astronomical sum of money, as this thing is apparently hard to manufacture.
Downstream targeting is also impossible at the moment. The best downstream target that might be doable before HMI would be Twist inhibition since that could be developed for treating cancer
So do we have drug that do that?
There is a patent for a Twist1 inhibiting peptide if you could find someone to make it. Hopefully there will be a small molecule inhibitor in the next couple years that will be easy to synthesize.