Category Archives: Wnt/Beta-Catenin

DKK2, Sarah Millar, Wnt/Beta-Catenin

DKK2 and Hairless vs. Hairy Skin

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Last week, researchers and scientists led by University of Pennsylvania’s Dr. Sarah Millar published a fascinating new open-access journal article titled:

“Regional Control of Hairless versus Hair-Bearing Skin by Dkk2.”

It seems like the researchers were trying to find an answer to an age old question: why don’t humans have hair on their palms and soles?

I always assumed that human beings and most other animals have no hair follicles and dermal papilla cells on their palms and feet/soles.

However, it seems like this is not true. You can get hairy palms and hairy feet based on just one slight genetic alteration (the removal of Dkk2). In fact, some animals such as rabbits and polar bears do have hairy feet/paws due to this very reason.

Dkk2: Remove it if you want Hairy Palms

Dickkopf-related protein 2 (Dkk2) is a protein that is encoded by the Dkk2 gene. This gene, when expressed in the palms and feet, works to inhibit Wnt/β-catenin signaling. This in turn results in totally hairless skin in those regions. The authors term Dkk2 as a Wnt inhibitor.

The Penn Medicine research team that led this latest research found that when they genetically removed Dkk2 expression from the plantar skin of mice, the animals began to sprout hair in this previously hairless area. This was due to the removal of Wnt signal inhibition.

Wnt/β-catenin signaling is crucial for hair growth in any area of the human body, and is the most researched subject area when it comes to the search for a hair loss cure. Not surprisingly, by now I must have written at least 50 posts on this blog in which I at least briefly mention Wnt/β-catenin or Wnt signaling.

Dkk2 Hairy Skin
Song et al., Regional Control of Hairless versus Hair-Bearing Skin by Dkk2, Cell Reports (2018), https://doi.org/
10.1016/j.celrep.2018.11.017

Dkk2 and Baldness

According to this article, Some studies have found correlations between baldness and DKK2 levels, but it is unclear whether this relationship is causal in nature.

According to Dr. Millar:

“We’re interested in taking a look at the precise nature in the difference in DKK2 in balding scalps versus normally-haired scalps,” Millar said. “We don’t know the answer yet.”

It is interesting that several companies over the years have worked on products that could both reduce body hair and increase head hair. The most famous of these is Follicum, although the company no longer seems to be working on a body hair reduction product.

Valproic Acid, Valproate, Wnt/Beta-Catenin, Wounding

Valproic Acid and Hair Growth

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Last year, I discussed new groundbreaking research from South Korea in relation to the development of a new peptide called  PTD-DBM. This product can activate the Wnt/β-catenin pathway and accelerate hair regrowth via wound-induced hair follicle neogenesis. One part of the findings also dealt with valproic acid and its impact on hair.

Valproic Acid and Hair Growth Research

In the above work that was led by Dr. Kang-Yell Choi, the researchers also found that topical valproic acid (VPA) sped up hair growth in mice. Valproic acid (also known as valproate and sodium valproate) is a medication that is used to treat epilepsy, seizures, bipolar disorder and migraines. However, this chemical can cause significant side effects and is not something to be take lightly.

In the past, there have also been other studies that found hair growth benefits of valproic acid (brand name Depakote). For example, these 2014 findings from South Korea suggest VPA grows hair in humans when used in a topical version.

Several other studies have indicated that valproic acid can change hair color and also change hair texture. However, most of the past research on this subject matter seems to be on small sample sizes. And a majority of these findings seem to be coming from one country: South Korea. Including these clinical trials from 2012.

Valproic Acid and Wounding

Early this week, commentator “John Doe” posted a link to an interesting new study titled “Transcutaneous implantation of VPA-encapsulated dissolving microneedles induces hair regrowth“.

Besides the discussion about valproic acid and hair growth, the study covers the fascinating phenomenon of this unique idea of valproic-acid-encapsulating dissolving microneedles (DMN-VPA). Apparently this method creates dermal micro-wounds than enhance the effects of the VPA upon hair growth. This also seems to support the wounding concept behind the technology of Follica.

Valproic Acid Hair Researcher Dr. Kang Choi.

One of the co-authors of this new paper is the same Dr. Kang-Yell Choi that I mentioned earlier in the post, and the research is yet again conducted in South Korea. Mr. Choi has his own wikipedia entry, and he deserves a photo in this post. He works at Yonsai University. According to the scientists behind this latest research:

“Micro-wounding-mediated implantation of DMN-VPA upregulates expression of Wnt/β-catenin pathway, alkaline phosphatase, proliferating cell nuclear antigen, loricrin and HF stem cell markers, including keratin 15, and CD34 more effectively than topical application.”

Injecting an Epilepsy Drug into the Scalp

At first, I was considering adding the above findings at the top of my next “brief items of interest” post. However, earlier today, my alerts notified me of a new article in newscientist magazine titled “Male balding may be cured by injecting epilepsy drug into scalp.”

I can not access the whole article, but it is about injecting valproic acid into your scalp to regrow hair. If anyone manages to read the whole article, please post about it in the comments. It seems like this predominantly South Korean led area of research is now finding its way into the US.

Valproate and Hair Loss

  • One unusual thing I noticed is that there are a lot of search results on Google that suggest valproic acid can also cause hair loss in people who are taking it orally for seizures and other such conditions.
  • One 2018 article found that oral valproic acid is more likely to cause hair loss. This valproate induced hair loss is typically diffused, nonscarring, and dose related.
  • A while back I covered a self-experimenter by the name “Swisstemples” in detail. One of the ingredients in his protocol is VPA.