University of California Los Angeles (UCLA) and University of Southern California (USC) are both based in Los Angeles, California in the USA. They have one of the most intense and historic rivalries in American college sports, especially in American football. The two campuses are separated by just 12 miles. In an amazing coincidence, the two most important hair loss research related discoveries in the world this month came out of these very two universities.
UCLA scientists find two new ways to activate hair follicle stem cells
For our purposes, the UCLA findings (published just today) seem to have the greatest significance. Scientists (led by Heather Christofk and William Lowry) have found two drugs that activate hair follicle stem cells in mice. Interestingly, both drugs are topical, and one (RCGD423) involves activating the JAK-STAT signaling pathway. No idea if this drug is connected to JAK inhibitors in any way, but that acronym keeps coming up regularly these days.
Both drugs involve increasing lactate production. Apparently, lactate production is strongly connected to hair follicle stem cell activation and hair cycling. In their initial research, the UCLA scientists blocked lactate production genetically in mice and found that this prevented hair follicle stem cell activation. Thereafter, they found that increasing lactate production genetically in mice accelerated hair follicle stem cell activation and increased the hair cycle.
RCGD423
The first drug, RCGD423, activates the JAK-STAT signaling pathway, which in turn leads to an increase in the production of lactate. This then activates hair follicle stem cells and also leads to quicker hair growth. UCLA holds the original patent for RCGD423, related to its ability to rejuvenate cartilage, and has filed a provisional patent for its use for hair growth purposes.
UK5099
The second drug, UK5099, blocks pyruvate (a glucose metabolite) from entering cell mitochondria. Interestingly, this forces an increase in the production of lactate in the hair follicle stem cells and therefore accelerates hair growth. UCLA has filed a provisional patent for using UK5099 for hair growth purposes.
Perhaps the most interesting quote from the earlier linked article summarizing these findings is: “I think we’ve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general“. On this blog, I have covered the connection between fat cells (adipose tissue) and hair growth numerous times due to significant recent research in that area. So I am not surprised at all that metabolism is also important when it comes to hair growth.
It is, however, surprising that hair loss research has uncovered so many new distinct pathways and mechanisms in the past few years. All of these are unrelated to the tried and tested method of targeting dihydrotestosterone (DHT) reduction. This is great news, since we already know that even close to 100 percent reduction in DHT will not bring back long-lost hair for most people, plus often comes with side effects.
USC scientists restore hair generation in defunct adult cells
A team of scientists from USC (led by Dr. Mingxing Lei, with collaboration from others in China and the UK) have managed to restore hair regeneration properties in adult mice cells that had stopped growing hair. A non-scientist friendlier summary of this work can be found here. One of the co-authors of this paper is Dr. Cheng-Ming Chuong, who I covered on this blog before.
Using intensive video analysis and documentation, bioinformatics, and molecular screenings, the scientists figured out a:
Molecular “how to” guide for driving individual skin cells to self-organize into organoids that can produce hair.
Also:
In the future, this work can inspire a strategy for stimulating hair growth in patients with conditions ranging from alopecia to baldness.
Very unlikely to come to fruition anytime soon of course, but considering that some of the research collaborators are from China… perhaps things may move faster than I am guessing if they could shift their research and potential clinical trials to that country?
I bet its “3-5 years away”
Great post admin.
To tie this together with last week’s post it should be mentioned that wounds exhibit large amounts of lactate. This helps stem cells know where to go. This ties in with microneedling actually.
Also, fasting (not eating for many days) elevates general lactate in humans.
Great points! Never knew that.
I can attest to this. Combined dermarolling with intermittent fasting, diet regulation and working out. Most of my hair has grown back. It’s remarkable that the diffuse thinning has reversed it more or less.
Very interesting. Could you add microneedling to PRP for a better result? Am trying to find the best way to help my shrinking hair follicles. My hair is getting very fine and am worried the follicles will start to die. Not sure how to get the right cure. Any suggestions past this – minoxidil worried and hope to find UK5099 and RCGD423 when they are available for consumer use.
Decades of research just to find the reason…just mutiply the hair follicles and implant them nothing else!
I still don’t understand why this hasn’t been done?
Greed and stupid research in the wrong fields…
I doubt they did much more than a year of research to come up with these findings. Brand new findings and not something repetitive from the past. How can you not get at least somewhat optimistic about two new drugs that could help with hair loss?
Admin. This is better than tsuji?.
Is a potencial cure?
Tsuji is aiming for 2020 commercial release. These guys? No idea.
Very interesting…egghead, sorry man way more than that.
Agree on metabolism front…
https://medicalxpress.com/news/2017-08-dallas-doctor-root-balding-graying.html
Covered on top here:
https://www.hairlosscure2020.com/brief-items-of-interest-may-2017/
I think this is a huge discovery and more attention should be given – especially in forums. After reading and researching, I have found that only UK5099 is for sale, and it’s costly. However, I am willing to buy it and try it out, but I need to know what dosage would be appropriate because at 10mg/$159 – it’s an expensive experiment to get wrong.
Buy: https://www.tocris.com/products/uk-5099_4186
The full article is behind paid walls, and I can rent it but not sure if they will find out that I saved it as PDF (I guess maybe I can get away with it if I disable Javascript?)
Research Paper: http://www.nature.com/ncb/journal/vaop/ncurrent/full/ncb3575.html
Lastly, brownie points to @Hairplz for making the connection between micro needling as well as fasting. To me, it all seems to be leading to an immune system problem as being the root problem. Any pointers would be good, and I can report back :).
They use a 20uM concentration of 5099, which they apply to the mice. Given that the MW of 5099 is 288g per mole, you could make 1.6L of 20uM solution, which is quite a lot. However, the shelf life in solution and at -20 is only a few months it looks like
How do you make a 1.6L of 20uM Solution. Say I buy this. How do you best apply. How much should be applied to the scalp.
Mage – Did yo purchase the UK5099 and how did you apply and did it work for you? Did you need to dilute the solution or were they tablets?
Many thanks, am thinking of purchasing also.
This might sound strange, but has anyone heard of studies performed with medicinal leeches? In my opinion medicinal leeches placed on thinning/balding parts of the scalp would work similar to PRP in that you’d have increased blood flow. Any thoughts?
I think Danny Roddy has been talking about lactate for years?!
Ties into my theory of lifestyle with suceptible genes being at the root cause of MPB with a particular relevance of sexuality and reproduction. I refer to studies which have shown a different hormonal response to ejaculation from sex to ejaculatio from self stimulation. We know the shift in hormones heightens DHT, spikes pro lactin and diminishes free T for up to 7 days. Now we know Lactate is needed for for stem cell activation in follicles. My thesis – lactate counteracts the activity of these hormones in the body, and when it isn’t present but there is a spike in DHT, Prolactin, the follicles are essentially free to attack. Try it – Quit whacking it for a week or two and see the difference in your hair.. My theory, which ties into this, sex is a strenuous activity involving accelerated burning of energy and therefore producing lactate. Jerking off, there’s no real energey expelled, so no lactate produced yet still upheaval in the hormones.
A controversial opinion, but my experience supports it though.
the USC research is pretty huge. Not in terms of like an immediate treatment but is a pretty big deal…and people on here go back to talking about dermarolling…
All researches are useless unless any medicine and treatment come out.
All comments are useless unless you say something of interest, or of humour
Gbh…so masturbating is worse for hair than sex ejaculation? Confused..
This is interesting. I have started to use Fenugreek to help with my hairloss because of the results of this guy –
https://www.google.de/amp/s/marstonblog.com/my-hair-is-thinning-on-top-im-trying-fenugreek/amp/
I am taking about 1200mg per day and I have felt a noticeable difference in terms of stopping shedding/scalp itch and hair quality.
Fenugreek is a weak DHT inhibitor, BUT also is use by women to enhance LACTATION – https://www.babycenter.com/404_can-the-herb-fenugreek-increase-a-moms-milk-supply_8880.bc
Perhaps fenugreek increases overall levels of lactate and hence is good for hair? I’m no scientist, but the link is interesting…
Very interesting! Please keep us updated about your results. Even just less itching would be great with a natural product.