A study in rodents is meaningless really
The fact that he mentions they will release it for Androgenetic Alopecia, as well as the slide near the end mentions topical JAK inhibitors for Androgenetic Alopecia (pg.17). That's promising.
“We will be developing a topical JAK inhibitor for androgenetic alopecia, and the data on that is quite interesting in that they found that the systemic JAK inhibitor does not work for that particular indication, but the topical does, mainly as a function of the target being more superficial in the skin and not really accessible from a systemic circulation. In vitiligo we have already seen a number of case reports demonstrating the utility of jak inhibitors...."
Well I was going to say how big a breakthrough this could be, but swoop seems to be saying its just the usual song and dance. Probably wont work that well if at all, and 10 years away if ever.
A study in rodents is meaningless really
What I got out of it was:
"To start looking and deploying capital against two new indications for us and that is androgenetic alopecia and also vitiligo. We will be developing a topical JAK inhibitor for androgenetic alopecia and the data on that (here clearly meaning on Androgenetic Alopecia) is quite interesting in that they found that the systemic JAK inhibitor does not work for that particular indication (still talking about Androgenetic Alopecia), but the topical does... "
Whether or not they have data on human applications well, they seem pretty confident in that it will work so let's hope it does.
@distracted, indeed, I could never know for sure. I find it extremely unlikely that JAK inhibitors will work for Androgenetic Alopecia, but we'll see. Clearly evidence is lacking with JAK inhibitors though (outside of mice), and this seems to be taken out of context. Hope it works though!! I would like to add that I don't want to be seen as a authority whatsoever. We are all equal here brahs unk:.
The more this story develops the more Im leaning towards the topical jak being combined with Follica's method eventually.
Have you ever posted a reason why you think that? If so, would you mind linking me to the thread?
Neither doctor said he believes the drug will work for the common kind of baldness that comes with age. Cotsarelis was adamant about it because male pattern baldness isn't related to the immune system. But King said he thinks conducting more research is worth a try.
We observed that topical treatment with JAK inhibitors resulted in more robust hair growth than did systemic treatment in AA, likely because it increases the local concentration of drug in the HF microenvironment, allowing both actions to occur.
[FONT=&]Next, to test a more clinically relevant route of delivery, we asked whether topical administration of protein tyrosine kinase inhibitors could reverse established AA in mice with kinetics similar to those of systemic delivery. In established disease, we found that topical ruxolitinib and topical tofacitinib were both highly effective in reversing disease in treated lesions (applied to back skin). A full coat of hair emerged in the ruxolitinib- or tofacitinib-treated mice by 7 weeks of treatment (data not shown), and we observed complete hair regrowth within 12 weeks following topical therapy ([/FONT]Fig. 4a,b[FONT=&]). Topical therapy was associated with a markedly reduced proportion of CD8[/FONT][FONT=&]+[/FONT][FONT=&]NKG2D[/FONT][FONT=&]+[/FONT][FONT=&] T cells in the treated skin and lymph node ([/FONT]Fig. 4c[FONT=&]), normalization of the ALADIN transcriptional signature ([/FONT]Fig. 4d[FONT=&]), reversal of histological markers of disease ([/FONT]Fig. 4e[FONT=&]) and correction of the GEDI in all treated mice ([/FONT]Supplementary Fig. 12[FONT=&]). Notably, untreated areas on the abdomen remained alopecic ([/FONT]Fig. 4a[FONT=&] and [/FONT]Supplementary Fig. 13[FONT=&]), demonstrating that topical therapy acted locally and that the observed therapeutic effects were not the result of systemic absorption.[/FONT]
Alopecia areata reversal was complete on both the back and belly, although the rate of hair regrowth was slower than with topical administration
"I agree 100% about IL-6-STAT3 being the main problem… but the question is, is it reversible? I tend to think yes also. Blocking AR, you still have a ton of pathways for IL-6/STAT3 and all of the other bad associated inflammatory agents working through STAT3 to continue the destructive path. The fact that different AR types for asians is not associated with a genetic risk for Androgenetic Alopecia, but the 20p11 SNP next to the FOXA2 gene is the number one at risk spot for them, as well as it being a very close 2nd to the AR for european ethnic people as far as genetic suseptibility to Androgenetic Alopecia, goes to show you that AR/DHT ISN’T OUR MAIN PROBLEM. Across ethnicities 20p11 shows the strongest link to baldness all ethnicities being considered. The FOXA2 gene right next to 20p11 regulates androgen metabolism and IL-6 response amongst many other things. IL-6 (know inflammatory agent) works through STAT3 and STAT3 can associate with cytokines like IL-6 through JAK or other pathways. IL-6 also is associated with PGD2 and DKK1. And STAT3 has been shown to increase Androgen receptor sensitivity and expression in prostate cancer, and even with castration (aka no more AR) STAT3 maintains cancer. STAT3 has also been shown to be a “go” and “stop” signal in different cell populations and when the balance is messed up it can cause cancer. STAT3 over-activation in the bulge makes keratinocyte stem cells change their behavior (look up the article on pubmed from 2015… “constitutive stat3 activation alters behavior of hair follicle stem and progenitor cell populations”). The cells it changes move ABOVE the bulge to and the markers they display are markers for IFE aka skin and cells known to turn into sebaceous gland cells. And JAK/Stat ablation has brought mice and humans back into the growing phase after inflammatory response. Not only this, but 20p11 is associated with a huge risk of idiopathic scoliosis which disproportionately effects adolescent girls, just like early hair loss disproportionately effects guys. A gender specific response on the same gene locus, during a period of growth (puberty). AND THE SAME SNP THAT GIVES THEM THE RISK FOR IDIOPATHIC SCOLIOSIS PROTECTS THEM FROM Androgenetic Alopecia.
What im saying is, it is OBVIOUS what the problem is now. AR susceptibility is just accelerating the process earlier in Europeans that JAK/STAT/IL6 would want to bring about anyways. It is reversibility that is the question. I for one DO NOT want to wait 10 freaking years for this to get through the FDA. Science has been focused on the wrong angle on this question for far too long. Thank god for Christiano’s insight."
"Great finds NASA!!! I read the abstract and briefly browsed through the longer of the two. Will read the entire thing later. I cannot believe that this was that long ago and nothing has been done about it since in regards to Androgenetic Alopecia. We have been slaying the androgen receptor angle for such a long time with such little results. It doesn’t even account for 20% of the variance in Androgenetic Alopecia. And is completely monomirphic in Asians. Their Androgenetic Alopecia is entirely caused by other gene locusts…. And typically occurs on average 10 years later than Europeans. Therefore whatever the mechanism(s) getting turned on in Androgenetic Alopecia are only being excellerated by the bad androgen receptor variant in Europeans. Not directly caused by the androgen receptor. It requires ANDROGENS (specifically DHT) but does not require the specific bad receptor. BIG DIFFERENCE. Looks like Androgenetic Alopecia has a large immune system component just like AA. So many important bits of info not just in these articles… Estrogen inhibits Il-6 and Androgen (especially DHT inducible miRNA-22) stimulates it. This explains why women lose hair at menopause despite declining test levels (bc estrogen protective effect is also declining). IL6 Causes premature Catagen and is induced by DHT in dp cells. Works through stat3 which can oversensitize and over-induce Ar expression. Stat3 is also responsible for the premature cellular senescence of DP (and other cell pops… It is a cancer protection mechanism trying to shut the cell down in the presence of ROS). Overexpression of keratinocyte specific mitochondrial stat3 causes slowed gene expression in direct energy unit of cell… Thus explaining why they cannot re-enter the hair cycle after a certain threshold has been reached… They are exhausted. Loses contact from arector pili…. Stat3 mediates muscle satellite helper cell regeneration…. And too much stat3 retards the process. Stat3 is needed for dkk1 in DP which messes with the beta catenin and Wnt pathways. The information is right in front of your guys’ faces. THIS IS IT AND NASA-RS WAS SPOT ON. They have found the needle in the haystack in my opinion. It’s the same one acting in AA and graft vs host disease… Both of which have stimulated hair growth topically with JAK inhibitors. They just have different patterns and time rates. This is going to work in Androgenetic Alopecia in a high concentration topical with effective delivery."
Seems more knowledge than Swoop.