Category Archives: Wnt/Beta-Catenin

CXXC5, Kang-Yell Choi, PTD-DBM, Wnt/Beta-Catenin

New Biochemical Material PTD-DBM to Target CXXC5

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Edit: It seems like this CXXC5 targeting study discussed in this post was first published in June 2017. Not sure why they now have a newer November 2017 publication date. Nor why the global media only covered it so intensively this past week.

A Reddit thread on this became very popular with over 2,500 comments.

Update: August 2020 — A new paper on KY19382 (a novel activator of Wnt/β-catenin signaling) was submitted in 2020 (approved in 2021). KY19382 works via the inhibition of the interaction between CXXC-type zinc finger protein 5 (CXXC5) and Dishevelled (Dvl). One of the authors is Dr. Kang-Yell Choi.

Update: February 2021: South Korean company CK Biotech is working on a CXXC5 product for hair loss via developing the PTD-DBM peptide. In February, 2021 they managed to raise $12 million in Series B funding. The company’s CEO is Dr. Kang-Yell Choi whose work I discuss later in this post. On their site, they discuss the CXXC5 and PTD-DBM per below:

CXXC5 and PTD-DM
CXXC5 and PTD-DM peptide for hair loss.

Last week, several of my alerts led to South Korean websites that discussed new successful local research targeting the Wnt pathway to reverse hair loss. Since I very recently wrote a post concerning the Wnt pathway, I was planning to save this news for my next “brief items of interest” post. However, four different readers commented about this news in the past week. And there are now many online news articles being published on this subject daily. So I decided to write a second post related to Wnt in less than a month.

Targeting of CXXC5 by PTD-DBM Causes Hair Regrowth

The actual paper was published in the prestigious Journal of Investigative Dermatology. South Korean scientists found that CXXC-type zinc finger protein 5 (CXXC5) is a negative regulator of the Wnt/β-catenin pathway. In fact, CXXC5 is upregulated in both thinning hair and arrector pili muscles in balding scalps. The lead author is Dr. Kang-Yell Choi.

The scientists managed to disrupt something termed as the “CXXC5-Dishevelled interaction” with a newly developed competitor peptide biomaterial called PTD-DBM. This resulted in activation of the Wnt/β-catenin pathway and accelerated hair regrowth and wound-induced hair follicle neogenesis in mice. Yet more evidence on the benefits of wounding?

Interestingly, at the start of the above paper, they also mention the famous hair loss researcher Dr. Luis Garza and his recent paper (co-authored with Dr. Dangwon Kim) titled “The Negative Regulator CXXC5: Making WNT Look a Little Less Dishevelled“. Perhaps Dr. Garza is also collaborating on this research?

Valproic Acid and Hair

Also of interest, the scientists added valproic acid into the mix and found that it sped up hair growth in the mice. There has been evidence on the benefits of valproic acid on scalp hair growth in the past. In fact a seminal work on the subject also came from South Korea in 2014, when scientists found that topical valproic acid increases hair counts in balding men. Apparently, valproic activates the activates the Wnt/β-catenin pathway (and inhibits glycogen synthase kinase 3β).

Dr. Kang-Yell Choi in South Korean Papers

Below are some of the online South Korean sites that covered this story. This research must be significant enough to be covered in so many local sources. Moreover, while the research team was led by Dr. Kang-Yell Choi of Yonsei University, some of the below sources suggest involvement of the South Korean Ministry of Science, ICT and Future Planning in this work.

Future PTD-DBM Drug Development

The UK’s Metro newspaper covered this story today. Key quote from Kang-Yell Choi, the main researcher involved:

“We have found a protein that controls the hair growth and developed a new substance that promotes hair regeneration by controlling the function of the protein. We expect that the newly developed substance will contribute to the development of a drug that not only treats hair loss but also regenerate damaged skin tissues”.

Mr. Kang-Yell Choi seems to have many patents related to the Wnt/β-catenin pathway to his name. He even has his own wikipedia entry.

Methyl Vanillate, Wnt/Beta-Catenin

Activation of the Wnt/β-catenin Pathway

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I have discussed the Wnt/β-catenin pathway and Wnt signaling numerous times on this blog in the past. This avenue of research is one of the most exciting ones in the hair loss world. It does not involve any kind of complicated cell multiplication and implantation type procedure.

If realized, the cure or treatment for hair loss that will arise from activating the Wnt signaling pathway (and subsequently maintaining the epithelial β-catenin signaling) will likely come from a topical product. A 2022 study from South Korea summarized the molecular mechanism behind various natural hair loss products that activate the Wnt/β-catenin signaling pathway.

Of note, defects in the workings of the Wnt pathway are implicated in numerous diseases and medical conditions. Therefore, there are numerous scientists around the world who are studying this important subject matter for non-alopecia related reasons.

Wnt/β-catenin Pathway Signaling and Hair Loss

  • By far the most well known company that is currently working on a topical hair loss drug via activating the Wnt pathway is Samumed. We eagerly await their publication of final Phase II clinical trial results and subsequent commencement of Phase III trials. I am on Samumed’s mailing list, but have received no recent updates. I am hoping it will happen any day now. Update: In 2022, Samumed (which became Biosplice) ended its work on the hair loss product. A massive disappointment.
  • In my last post, I mentioned that Dr. Antonella Tosti is presenting a paper titled “A new topical Wnt/beta-catenin activator in the treatment of men with male pattern hair loss”. I wondered what topical this would be, and commentator “Bob Ross’s Hair” hypothesized that it is methyl vanillate based on this study from 2016 in which Dr. Tosti is a co-author.
  • Related to the above, Dr. John Cole’s staff recently wrote a blog post on their new WNT Act product for sale in the US. This product contains methyl vanillate. Dr. Cole has collaborated with Dr. Tosti many times in the past and mentioned this in his interview on this blog. It seems like the Deltacrin WNT product sold in Italy is the exact same thing as the WNT Act product being sold in the US. On the US product’s Amazon page, they claim a 7% increase in hair density and a 10% increase in hair diameter.

JW Pharmaceutical

Update: July 2023 — See my new post on JW Pharmaceutical.

Commentator “Donitello” who often posts nonsense did surprise me and found a gem early last week. A South Korean company named JW Pharmaceutical (in partnership with the University of Pennsylvania and Dr. George Cotsarelis) is developing a topical Wnt signal activating product to tackle hair loss.

The product is currently known as CWL08006, and the company aims to start pre-clinical trials in 2019. Apparently JW Pharma has been conducting research on the Wnt pathway since the early 2000s, and currently holds numerous patents and rights to proprietary compounds in this area.

Update: October 2022 — JW Pharma will present preclinical results of its Wnt hair loss treatment “JW0061” at the Wnt 2022 conference to be held in Japan from November 15th. Note that these results are based on animal models.

JW0061 is a substance that promotes the differentiation and proliferation of hair follicle stem cells that are involved in hair growth. It does this by activating the Wnt signaling pathway, which stops working correctly during the process of hair loss.

Update: November 2022 — Above now confirmed. JW made a presentation on its newly identified Wnt-modulating small molecule “JW0061” at the “Wnt 2022 conference. It demonstrated preclinical efficacy for hair regeneration. According to preclinical data, JW0061 activates the Wnt signaling pathway by directly binding to the GFRA1 protein in dermal papilla cells.