Yesterday, Reddit PLOS Science Wednesday AMA (Ask Me Anything) had a highly unusual session with two hair loss experts: Dr. Zhengquan Yu and Dr. Maksim Plikus. Official citation link is now here. While the title of the session only mentioned Mr. Yu, the two experts spent an equal amount of time answering questions.

MicroRNA (miR-22) and Hair Loss

Earlier this year, Mr. Yu co-authored an important paper on the influence of microRNA (miR-22) in hair loss in mice that was published in PLOS.

Update: July 27, 2020 — New study from North Carolina State University finds MicroRNA (miR-218-5p) shows promise for hair growth.

Surprisingly, Mr. Yu is an associate professor at the China Agricultural University, one of the last places where you would expect to see research on hair loss. I found it funny that somewhere in the AMA, Mr. Yu mentions the potential for creating hairy goats!! Several days ago Chinese scientists also announced the creation of genetically modified tiny pigs to keep as pets. One day I should fly over to China to see where all the secretive hair loss research is taking place.

Dr. Maksim Plikus and Dr. Zhengquan Yu on Reddit

While Mr. Plikus was not a co-author of the above paper, his responses on the Reddit were quite thorough and interesting. I did not realize the huge amount of work that he has already done on hair loss related research. Mr. Plikus is an assistant professor at the University of California Irvine.

Getting back to the Reddit AMA, some of the more interesting Q&A’s:

Question from “Wkbrdnjoe”: “Now that you guys have found positive results in mice, what is the next step? Testing humans?”

Answer from Maksim Plikus: “Mouse findings would certainly have to be validated in humans. Currently, pilot testing on human hair follicles is possible using two experimental approaches: (i) organotypic hair follicle culture, and (ii) human-on-mouse xenografts. Anagen phase hair follicles, including human follicles, can continue to grow in vitro under specialized culture conditions for approximately one week.

Human hair follicles grafted on immune compromised mice can grow for many months, imitating their normal, long-lasting anagen phase.  Both approaches are widely used in human hair follicle research.  Importantly, human hair follicles significantly differ from mouse in terms of signaling regulation. For instance, while human hair follicles are highly sensitive to androgen signaling, mouse follicles are not. Therefore, mice can not recapitulate the pathogenesis of human androgenetic alopecia.”

Later on, Maksim Plikus responds to a lengthy question from famous hair loss forum member “Swooping” with the following:
“Your knowledge on androgenetic alopecia already appears to be pretty extensive. As you can appreciate, it has a complex mechanism, therefore many if not all factors that you mentioned are probably involved in its pathogenesis. What is important is to figure out which ones are upstream and which are downstream. This would affect the therapeutic potential of the targets.

As I already mentioned in another reply, rodents and mice specifically, are not an appropriate model for studying androgenetic alopecia. Mouse hair follicles grow very differently from human scalp follicles. Mouse dorsal hairs grow only for about 2 weeks and attain 0.7-1cm in length. This is equivalent to human scalp vellus hair. Moreover, mouse follicles do not respond to androgens the same way human follicles do, and mice do not develop androgenetic alopecia in response to testosterone treatment. This limited the research progress in androgenetic alopecia field. However, we now have organotypic culture system and human-on-mouse xenograft model that can be used for studies on human follicles.”

And the most optimistic response from Maksim Plikus: “Recent studies showed that dormant hair follicles in patients with androgenetic alopecia maintain their key stem cell population. Please refer to this study. This suggests that as long as the signaling mechanism of androgenetic alopecia pathogenesis can be interrupted, dormant scalp hair follicles can regrow. For instance, this 2003 study showed that grafting of vellus human scalp follicles onto mouse partially restores their normal growth characteristics: link.”

Some quotes from Zhengquan Yu regarding his work on miR-22:

“Based on this study, miR-22 antimir could be an effective drug for hair loss.”

“miR-22 antagomir or other anti-miR-22 oligonucletides could be used to inhibit miR-22 function, which would prevent hair loss or maintain prolonged follicle life.”

“I think that our findings provide a new therapeutic target to treat hair loss in way of microRNA. The cause of hair loss is pretty complex, it is hard to develop effective treatment for all patients. However, inhibition of miR-22 could benefit a certain number of patients whose hair loss caused by increasing miR-22.”

— Some more detailed technical responses are in the AMA that I will not paste here, including many links to studies related to the complex genetics involved in MPB, plus discussions on qorum sensing, signaling and more.