Activating Pathway Could Restart Hair Growth in Dormant Hair Follicles

Stem cell; cell based hair therapy
1

This is kind of old news (December 2013), but relates to another discovery at the University of Pennsylvania

“A pathway known for its role in regulating adult stem cells has been shown to be important for hair follicle proliferation, but contrary to previous studies, is not required within hair follicle stem cells for their survival, according to researchers with the Perelman School of Medicine at the University of Pennsylvania. A new study, published in Cell Stem Cell, identifies a molecular pathway that can be activated to prompt hair growth of dormant hair follicles, or blocked to prevent growth of unwanted hair.”

http://www.uphs.upenn.edu/news/News_Releases/2013/12/millar/

2

Apologies if this has been posted elsewhere in the forum, I just read it today, it might be of interest to you Roger.

In experiments described this week in Cell, Hsu disabled TACs’ ability to produce the Sonic Hedgehog protein by knocking out the gene responsible in the hair follicles of adult mice. As a result, the proliferation of hair follicle stem cells and their TACs are both compromised. They further showed that it is the quiescent stem cell population which requires Sonic Hedgehog directly for proliferation.

Surprisingly, when Hsu blocked the ability of the quiescent stem cells to respond to Sonic Hedgehog, hair growth proceeded, but follicles were shorter, and with each round of hair cycling, the quiescent and primed stem cell populations were diminished, until hair regeneration failed altogether. These features are remarkably similar to what happens in male pattern baldness, according to the researchers. Although the root of this disorder may be further upstream than Sonic Hedgehog, this study provides new insights into the manifestations of hair loss, which in the long run will be necessary to develop new therapeutics,

3

You guys are on the right path in this thread. The Wnt pathway is well known to be necessary for hair follicle differentiation, and loss of Wnt signaling blocks formation of hair follicles. Shh signaling is downstream of Wnt but the same holds true, it is necessary for hair development. Both Wnt and Shh are also necessary for the proliferation of cells in the matrix of the hair follicle–loss of either, but especially Shh, prevents proliferation. Mutations in the promoter of the Wnt10a gene that cause a decrease in expression have been tied to androgenic alopecia leading to the belief that a lack of activation by the Wnt pathway is a major cause of AGA. Find a way to stimulate the matrix cells with wnt agonists but not affecting the stem cell population and you will likely have a very good hair loss drug. You want to avoid the stem cell population because you don’t want to deplete the cells that contribute to further hair growth too quickly. This may be accomplished simply by lowering the dosage of a wnt activator (like BIO or LiCl) because the stem cells are more refractory to wnt stimulation than the transient amplifying cells (TACs).

4

I don’t believe targeting the SC’s will lead them to deplete…

In any case, we have Wnt agonists available, and voila:

Here’s a paper that shows hair growth in humans. Not mice!

Topical valproic acid increases the hair count in male
patients with androgenetic alopecia: A randomized,
comparative, clinical feasibility study using phototrichogram
analysis
https://anonfiles.com/file/e467c75e9dac65fbc1f9a95385ab81f2

(Don’t click the blue button, click the black one)

5

Valproic acid is already FDA approved and widely used as an anti-seizure medication, it would be easy for doctors to repurpose it and prescribe it as a topical.

6

Precisely! While it is not “the cure”, every little bit helps.