View Full Version : Blocking enzymes in hair follicles promotes hair growth
10-23-2015, 02:47 PM
New research tested in normal hair follicles, they are now moving forward to test this in hair follicles affected by AGA.
Sivan Harel1, Claire A. Higgins1,*, Jane E. Cerise1, Zhenpeng Dai1, James C. Chen1,2, Raphael Clynes1 and Angela M. Christiano
Pharmacologic inhibition of JAK-STAT signaling promotes hair growth
Two JAK inhibitors have been approved by the U.S. Food and Drug Administration. One is approved for treatment of blood diseases (ruxolitinib) and the other for rheumatoid arthritis ( )
As far as iI remember ruxolitinib and tofacitinib have unpleasant side effects.
10-23-2015, 03:17 PM
Great Soge! It seems that it could may be work for AGA aswell
"What they found was the drugs were affecting the hair follicles directly"
"Male pattern hair loss follicles are stuck in the same state where these drugs seem to work."”
they tested on AA patients and it seems to work
other researchers aswell: http://www.ebiomedicine.com/article/S2352-3964(15)00063-8/abstract
Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib
It seems really powerful drugs. We would not have reversal like AA but maybe it could really help slowing the loss
10-23-2015, 05:38 PM
Thanks Sogeking. Very interesting. See how she also says that there are no good animal models for AGA and that this is a major hurdle. I would like to touch a bit on what you posted.
In AA (alopecia areata) cells start attacking the hair follicle. It's auto-immune related. Hence several compounds that regulate the immune response have shown to be (somewhat) effective in AA already. Think of corticosteroids and topical immunotherapy. See here for a picture that somewhat reflects a treatment protocol to date for AA; http://ars.els-cdn.com/content/image/1-s2.0-S2210836X13000237-gr5.jpg.
Indeed they have discovered that a compound is apparently even way more effective in treating AA and again it's a compound that alters the immune response. This is what people need with AA anyway. They need to stop these cells from attacking the hair follicle. It's really great for those people that perhaps in the near future a even more effective compound will probably come through.
However in relation to hair follicle cycling in humans actually and compounds that alter the immune response there is something interesting. Some of them have actually shown to alter hair follicle cycling in humans. Think of betamethasone and cyclosporine (which have shown to be effective for AA too to some extent).
For instance if we look at studies for cyclosporine;
Hypertrichosis is a cosmetically undesirable side-effect of cyclosporine therapy. A study of 56 insulin-dependent diabetics on long-term cyclosporine therapy indicated that unequivocal hypertrichosis occurred in 94.6% of the patients. Occasionally, patients exhibited marked hypertrichosis and some experienced adverse social problems resulting from this side-effect.
These patients were followed up for median period of 22.4 months. Hypertrichosis was seen in 56 males (88%). All the 17 female patients (100%) developed hypertrichosis. It disappeared in all after stopping Cyclosporine - in around 3 to 7 months. Hypertrichosis was the primary indication for stopping Cyclosporine in 15 (23.8%) of them. Acne developed in 66 patients (82.5%). However, gum hypertrophy was seen in only three patients (3.75%).
Well a google search shows there are enough cases or studies confirming this. This brings me up to the point that I think is important; Modulation of hair follicle cycling doesn't have to help with AGA at all. Simply because we are not dealing with "healthy" hair follicles.
On a healthy scalp approximately 7-15% of hair follicles reside in telogen. Modulation of hair follicle cycling might actually push these hair follicles in anagen giving you more actively growing hair follicles. But that doesn't mean that it will be also able to push a unhealthy miniaturized hair follicle into anagen. Other body parts have a higher telogen % and longer telogen. I know people have tried cyclosporine on their scalp, it didn't yield much effect. In fact there have been even some studies;
Yet it is able to induce quite heavy hypertrichosis on other body parts sometimes.....
Anyway they are very potent drugs indeed and perhaps they might do something good for AGA too but I would like to see evidence on humans instead of mice. I think we all do :p.
Btw, didn't hellouser plan to use or used one of these compounds?
10-23-2015, 08:09 PM
A good summary:
10-23-2015, 08:50 PM
Tofacitinib treatment promotes inductivity of DP
Because phospho-Stat5 is strongly expressed in mouse DP in catagen and telogen (Fig. 2D), we confirmed that phospho-STAT3 is present in the dermal sheath and DP of human HFs in anagen and phospho-STAT5 expression is weakly present in the top portion of the DP (fig. S4D).
We recently demonstrated that growing human DP cells in three-dimensional (3D) spheres improves their capacity to induce HF growth (31). To examine the effects of JAK inhibition on the potency of HF induction, human DP spheres were cultured with vehicle control, ruxolitinib, or tofacitinib and then combined with neonatal mouse keratinocytes and injected into nude mice. This patch assay has been shown to recapitulate HF morphogenesis and serves to evaluate trichogenic capacity (32). We found that tofacitinib-treated human DP spheres induced larger and significantly greater numbers of HFs overall (P = 0.00013) (Fig. 3D), suggesting that the inductivity of human DP is enhanced by inhibition of JAK1/3 signaling.
Treating DP spheres with tofacitinib increased the inductivity of cultured DP by targeting some of the pathways not previously altered by the 3D culture condition (T2 and T4). Blue, gene expression within territories corresponding on noninductive state; red, gene expression within territories corresponding to inductive state. Although tofacitinib restores genes within T2 and T4, restoration is incomplete compared to fully intact DP (territories in bright red).
10-24-2015, 02:59 AM
That's pretty cool stuff. in Hairlosscure2020.com someone wrote in the replies for this article that he had TOFACITINIB and would going to test it topically...
But if this drug fights cancer, wouldn't it be full of side effects? but really bad ones...?
10-24-2015, 04:15 AM
Exactly Swooping, so far they haven't tested this on AGA affected hair follicles. But it would be good if they test it on humans themselves.
If this works as a growth promoter for AGA good news is that ruxolitinib and tofacitinib are already FDA approved for other ailments.
Bad news is that side effects are a major concern.
Immunologic side effects have included herpes zoster (shingles; 1.9%) and case reports of opportunistic infections. Metabolic side effects have included weight gain (7.1%). Laboratory abnormalities have included alanine transaminase (ALT) abnormalities (25.2%), aspartate transaminase (AST) abnormalities (17.4%), and elevated cholesterol levels (16.8%). Other common adverse events are anemia (low red blood cell count) and thrombocytopenia (low blood platelet count). Grade 3 to 4 anemia occurs in up to 45% of patients and grade 3 to 4 thrombocytopenia occurs in 10% to 15% of cases, and requires medical intervention to return to near-baseline levels.
Xeljanz is required to have a boxed warning on its label about possible injury and death due to problems such as infections, Lymphoma and other malignancies which can arise from use of this drug. Serious infections leading to hospitalization or death, including tuberculosis and bacterial, invasive fungal, viral, and other opportunistic infections, have occurred in patients receiving tofacitinib. Epstein Barr Virus-associated post-transplant lymphoproliferative disorder has been observed at an increased rate in renal transplant patients treated with tofacitinib while on immunosuppressive medications.
So really "fun" stuff.
10-24-2015, 06:11 AM
Those medications (arthritis?) have been mentioned plenty on these boards and they are definitely not something I'd want to take. Also it's mice so... growing hair on a mouse is no achievement these days. Maybe there's a lesson to be learned from this stuff but this is no 'cure'.