Disease Model Validit y

As we decide how to allocate our treasury, the testing models we use have fallen under question. The conversation began with our dutasteride delivery vehicle research, led by Herber t. Dr. Cornelia Keck pitched us on running our delivery vehicle study on ex vivo porcine ear, highlighting the pig ear’s similarity to in vivo human skin She doesn’t like the Franz diffusion model, as stretching the skin changes its mechanical proper ties Geoff Hamilton fur ther advised on the pig model, warning us to beware of Epibiotech’s recent pig results–their paper failed to disclose the drug used to immuno-suppress the pigs, a significant omission for any reputable research organization While perfected drug delivery–achieving a localized effect with no systemic exposure–remains of utmost impor tance, our model to test a drugs’ clinical efficacy differs substantially.

In drug efficacy, Jumpman, Ralf, Herber t, Bob allen, and Benjels continue to lead us. The animal whose balding genetics most closely mirrors ours is the stumptail macaque, with Bob allen highlighting that both Minoxidil’s and Finasteride’s efficacy in macaques approximately mirrored their human results. A pressing question in the hair loss community remains whether HMI-115’s Phase 1 clinical trials will mirror their macaque study Potential Dingo, Macaque, and Tigris repor ted we should receive their results in September or October RU58841 also successfully passed the macaque test, although we still do not have its official, yet unreleased, Phase 2 trial data (Phase 2 trials show efficacy; Phase 1 trials show safety). If only someone would build the tools for us to aggregate patient treatment data.

Outside of the macaque, the two most impor tant models remain human scalp skin ex vivo tests, either on murine back or cultured in a dish Additional models, such as skin organoid models and dermal papilla cells in a dish, often fall shor t, as the transcriptomes and intercellular communications–or lack thereof–deviate too far from human in vivo The community’s final conclusion is that Jumpman’s gigabrain knows best–there is no model better than human in vivo. The only question is when is most economical–both for patient safety and hair regrowth efficacy–to turn on the switch.

Contributors: Jumpman, Ralf Paus, Herber t, Potential Dingo, Bob allen, Geoff Hamilton, Andy1, Macaque, Vincent, Benjels, Tigris, Visangle, Averbs123, and Ghter

Synthetic Pug discovered that only a few dermal papilla cells can make all the difference–answering our questions on the ability for HMI-115 to sufficiently regrow hair within only six months of use in macaques. HMI-115’s treatment works as a prolactin (PRL) receptor blocker, administered as a monoclonal antibody injection in the stomach. There has been significant speculation on the success of HMI-115, due to repor ted results from its ongoing Phase 1 clinical trial and its impressive pre-clinical macaque study As Dingo, Macaque, and Tigris repor ted, we should receive our results of the Phase 1 androgenetic alopecia trial in September or October of this year.

Despite HMI-115’s success thus far, one can have upregulated prolactin levels and still experience significant hair regrowth–in fact, prolactin stimulates hair growth in females Ghter has been taking 2mg of prolactin a day and his hair is looking way better We thus are left to question whether PRLR is either a sustainable long-term treatment or a co-activator in another, more impor tant pathway. Jumpman ideated a study on the measurement of the downstream genomic changes of PRLR inhibition on the novel pathway’s mechanism of action.

We also remain cautious of the systemic effects of the drug and thus advise self-experimenters to exercise caution at home. Prolactin helps maintain healthy neurochemistr y, protection against fatty liver disease, and is necessary for sexual function. HMI-115 is also in Phase 2 trials for endometriosis, a female reproductive disease, eerily similar to Finasteride’s use in the male reproductive system. We need more data to understand PRLR’s science, due to its truly novel approach in the treatment of androgenic alopecia.

Fun fact: Patients currently in HMI-115’s clinical trial are paid $2k USD