1. A stable antibody-containing liquid or lyophilized formulation comprising 20-120 mg/ml antibody wherein the antibody is the PRLR antibody mat3, comprising
a. 10 - 50 mM arginine HC1
b. 5- 30 mM histidine
c. 1-10 mM methionine
d. 50-150 ppm non-ionic surfactant
e. 34-292 mM sugar,
for the use in treating male and female pattern hair loss.
Looks like that's all we need, and to figure out the correct dosage. Every two weeks, but how much? 30mg was enough in the endometriosis study, but the patent indicates a much higher dosage.So what information are we missing in regards to the prl antibody formulation?
N/C terminus still?
Dosage is specified in the patent 20-120 mg/ml
Looks like that's all we need, and to figure out the correct dosage. Every two weeks, but how much? A minimum of 30mg.
Dosage is specified in the patent 20-120 mg/ml
«Within other aspects, the anti-PRLR antibody formulation contains about 5- 30 mM histidine, about 34-292 mM sucrose, about 50-150 ppm polysorbate, about 10-50 mM arginine, about 1-10 mM methionine, about 20-120 mg/ml anti-PRLR antibody at a pH ranging from about pH 5.0 to about pH 6.5, such as pH 5.5»
Update: they list multiple dosages, not just this one. But gives us a ballpark dosage.
Multiply by .324 for the human dosage, and you get 12.96mg/kg, but that is very high compared to other studies in humans. That has to be the antibody concentration, and not the actual dose. As of now I would go with 30mg every two weeks to be safe. That showed a high serum concentration in the endometriosis trial.The animals received 40 mg/kg PRLR antibody mat3 subcutaneously twice a month.
Subcutaneous. It just needs to be in the bloodstream.Well, I know how I'm going to be spending my evening tomorrow doing then. Searching high and low.
What about administration for hair loss? Subq? or would scalp injections with a meso-gun do the job as long as its hitting the bloodstream?
Prolactin has effects on both estrogen and androgen expression, so it's logical to assume that the antibody's effects are mediated through normalizing them both somehow, but I won't guess at the exact mechanisms. The antibody does work better in younger monkeys, but it even works on areas that have been bald for a decade.So my best guess is that elevated prolactin can cause androgen excess (through adrenal androgen to stronger androgen conversion in tissues most likely) and make balding worse. Could explain why serum DHT suppression is not enough for some people. Maybe there’s an underlying pathway that prevents regrowth of hair even after finasteride. Could also explain how RU works well in some people since it would also clean up other androgens through other pathways.
But if this antagonist closes off that pathway before it needs to be “cleaned up” it may be more effective
It could end up shelved for Androgenetic Alopecia due to side effects, but it looks effective against some cancers too, so that likely will be approved eventually. As long as it's approved for something we can gain access to it for our hair.This seems to be promising, I'm most pleased about the use of macaques and their response to the drugs. Hopefully this goes somewhere, seems as if it really can be effective if testing is not stopped prematurely.
If you are right then BAY is just the inhibitor. But DEL is the protein with super power and that is why you need tons of it to overcome the weak one. Do you use BAY to lower weak protein production while you pour buckets of DEL? Also if DEL is just a protein then it is strange to hear it will stay active for years. And finally the gland and tissues producing proteins could be reprogrammed to generate the immune one?So it actually makes a lot of sense now. del 1-9 G129R hPRL stands for: deleted 1-9 N-terminus G129 Mutation human recombinant prolactin.
«As highlighted by its name, Del1-9-G129R-hPRL is a hPRL core protein containing two modifications: deletion of the nine N-terminal residues, and substitution of Gly129 for an Arg (5).»
Basically it’s a prolactin protein that’s been enginereed to be fucked up.
Disclaimer, I may be wrong though. Need confirmation on this.
See the last comments. The sequence of mat3 I posted first is probably the one. Forget about the DEL, it’s half life is 20 minutes. BAY is the mat3.If you are right then BAY is just the inhibitor. But DEL is the protein with super power and that is why you need tons of it to overcome the weak one. Do you use BAY to lower weak protein production while you poor buckets of DEL? Aldo if DEL is just a protein then it is strange to hear it will stay active for years. And finally the gland and tissues producing proteins could be reprogrammed to generate the immune one?
PRL is the central neurohormone of the hypothalamic‐pituitary axis (HP axis) and is released from the pituitary upon hormonal stimulation. Beyond lactation, PRL has well‐recognized functions in the regulation of a variety of biological processes, such as angiogenesis, adipogenesis and the immune response.[67-69] Its relevance to HF biology has been equally well documented. For more than 30 years, PRL has been recognized as a potent (seasonal) hair cycle regulator in mammals and extensive research has been conducted into its effects on human hair growth.[70-73] The gene that encodes PRL is located on chr. 6p22.3 and lies within 500 kb of an Androgenetic Alopecia risk locus on the same chromosomal band (lead variant: rs6935891; P = 3.0 × 10−39, β = −0.05, SE = 0.004).[12, 24] Given the fact that PRL and its receptor are expressed in human HFs and that their paracrine and autocrine effects on hair cycle control and hair growth are well recognized, PRL represents a promising candidate gene for the hair growth defects observed in Androgenetic Alopecia‐affected HFs. Moreover, PRL stimulates adrenal androgen production and elevated PRL levels have been reported to be accompanied by hirsutism and hair loss from the scalp, which resembles the pattern observed in Androgenetic Alopecia.[74-76] Also notable in the context of Androgenetic Alopecia is the observation of sex‐ and location‐dependent hair growth regulatory effects for PRL in studies of human ex vivo HFs. While PRL promoted hair growth/hair shaft elongation in HFs derived from female frontotemporal scalp, PRL treatment of isolated male occipital scalp HFs resulted in premature catagen induction and thus the inhibition of hair growth. This observation has been further substantiated on a molecular level, since PRL treatment resulted in sex‐ and site‐specific differences in gene expression. Furthermore, analyses of plucked HFs from male frontal and occipital scalp revealed differential expression for several microRNAs (miRNAs) that target PRL signalling. Together, these findings suggest that PRL action may contribute to the observed differences in Androgenetic Alopecia susceptibility between frontal and occipital HFs and the resulting characteristic hair loss pattern. Though PRL has a reported stimulatory effect on HF stem cell‐associated keratins located in the outer root sheath in HF cultures of isolated female HFs , it is tempting to speculate—especially given the reported sexual dimorphism of PRL action on the HF—that PRL might have an inhibitory effect on stem cell function in male HFs, which could result in the stalled growth observed in miniaturized Androgenetic Alopecia HFs.
It has to be mentioned in one of the other patentsSo what we are missing now is the N and C terminus. It's not mentioned in the patent as far as I can see. But wouldn't it make sense that the N and C terminus is identical to PRLN itself? In order to bind to the prolactin receptor. In the patent they kind of point out the negatives about the del antibody, that has deleted n terminus. Indicates that the n terminus is fully intact as in the PRLN.