Category Archives: Wnt/Beta-Catenin

Ear Hair Cells, Frequency Therapeutics, Progenitor Cells, Wnt/Beta-Catenin

Ear Hair Cell Regeneration and Frequency Therapeutics

98 Comments

Update: April 19, 2022 — Scientists from Harvard Medical School have managed to regenerate inner ear hair cells that enable hearing (h/t “Rali”). They claim to have moved closer to a gene therapy solution for sensorineural hearing loss, although no human clinical trials have started as yet.

The research team was led by Dr. Zheng-Yi Chen. They reported creating a drug-like cocktail of different molecules that successfully regenerated hair cells in a mouse model by reprogramming a series of genetic pathways within the inner ear. The full study was published on April 17, 2023 in PNAS.

Note that the team identified and used a combination (cocktail) of drug-like molecules that was composed of small molecules and siRNAs. Make sure to read my past related posts on siRNA as well as on creating the ultimate hair loss drug cocktail.

Frequency Therapeutics

Update: April 21, 2023 — Frequency Therapeutics phase IIb clinical trial results for FX-322 have been officially posted. A total of 142 adult patients were involved, 72 of whom got the placebo. The remaining 70 got a single intratympanic injection of FX-322 (laduviglusib 0.628 mg/sodium valproate 17.72 mg) into their hearing loss affected ear.

In February, the company announced that these trials did not succeed and the company’s stock price subsequently collapsed.

Update: March 29, 2022 — Update on MIT spinout Frequency Therapeutics and its drug candidate that stimulates inner ear hair cell growth.

February 21, 2017

An interesting new article titled “Drug treatment could combat hearing loss” seems to have little bearing with scalp hair loss. However, hearing loss is usually caused by permanent damage to many of the 15,000 hair cells in each inner ear. Regenerating those with this new drug therapy could also indicate a similar potential for regenerating scalp hair cells.

In the article, the author discusses a new paper that is published in the February 21 issue of Cell Reports. In fact, the findings of this paper are so important that the cover page of the journal has a photo taken directly from the research. Note that the lead scientists are also working on this technology via a new company called Frequency Therapeutics.

Ear Hair Cell Growth

Ear Hair Follicle Regeneration

In this paper, a team of scientists (from MIT, Brigham and Women’s Hospital, and Massachusetts Eye and Ear) have found a way to regenerate tiny inner ear hair follicles via a drug combination treatment.

This combination is a two step process where in the first step, a combination of drugs expands the progenitor cell population. In the second step, another combination of drugs induces the new cells to differentiate into hair cells.

In one variation of the experiment, the second step was not even necessary because “once the progenitor cells were formed, they were naturally exposed to signals that stimulated them to become mature hair cells”.

I am pretty certain that I have read articles in the past about ear hair cell regeneration. I might even have mentioned one or two of them in passing on this blog before. However, this particular article and associated study warranted its own separate post and stuck out for two key reasons:

  1. The researchers succeeded in regenerating mouse ear hair cells via creating new progenitor cells. This is quite astounding to me because in regular scalp hair loss, scientists have found that hair is not lost due to the death of hair cells, but rather, due to the death of progenitor cells. So if these scientists can create new progenitor cells in the ear that lead to ear hair regeneration, I do not see how they can not try to use the same method to create new progenitor cells in the scalp.
  2. The researchers accomplished their potentially ground breaking achievement via stimulating the Wnt signaling pathway. I have discussed that pathway numerous times on this blog in the past, since it seems to be crucial for scalp hair growth. Moreover, well known company Samumed’s hair loss drug is targeting that same pathway.

Will ear hair cell research and findings become applicable towards scalp hair cell research? I really hope so, and this new work is encouraging due to the involvement of the Wnt/Beta-Catenin pathway.

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

CK Regeon and its Hair Loss Peptide

3 Comments

In 2017, I covered the development of a new biochemical peptide material called PTD-DDM that would grow hair. The peptide targets the CXXC5 gene, resulting in activation of the Wnt/β-catenin pathway. This is turn leads to accelerated hair regrowth.

The South Korean team that conducted this research was led by Dr. Kang-Yell Choi, who even has a wikipedia entry. I previously also covered Dr. Choi in my post on valproic acid and hair growth.

CK Regeon

To bring this hair growth peptide (KY19382) to market, Dr. Choi started a company named CK Biotech that I mentioned in my original post. However, in 2021, it was renamed to CK Regeon.

Recently, I heard again about this company due its presentation at a June 30, 2022 South Korean symposium on the development of innovative new drugs for hair loss. This conference was led by Epibiotech and Yonsei University. On an interesting side note, Inventage Lab also presented at this conference, indicating that finasteride injections are still on track.

CK Regeon
CK Regeon. Dr. Kang-Yell Choi’s new company targeting CXXX5 inhibition in order to restore Wnt/beta-catenin signaling.

Make sure to read CK Regeon’s regular press releases. On Linkedin, the company currently has 8 employees. On the company’s Twitter page, they keep sharing an updated infographic on the benefits of Wnt pathway activation. The latest heading:

“WNT Pathway restoration, a therapeutic target for tissue regeneration, diabetic wound healing, hair growth, non-alcoholic steatohepatitis (NASH), obesity and diabetes.”

On the company’s target diseases page and pipeline page, they include the above conditions as well as “countering short stature” and treating Alzheimer’s disease.

While I doubt that CK Regeon can cover all these bases, it is not surprising that the Wnt/Beta-Catenin signaling pathway is so crucial to human health.

Blocking CXXC5 and Improved Wnt/Beta-Catenin Signaling

Previously, we got excited about the potential of Samumed in curing hair loss by activating the Wnt pathway. Unfortunately, this company did not pan out after years of favorable publicity.

Another company named Frequency Therapeutics is trying to regrow inner ear hair cells via stimulating the Wnt signaling pathway. Fractional lasers and wounding also work on the same pathway, leading to a regrowth of scalp hair in some who are lucky.

CK Regeon’s overall technology entails blocking the CXXC5-Dishevelled (Dvl) protein-protein interaction (PPI). This is accomplished via the creation of new small molecules or peptides. This inhibition of CXXC5 results in restored Wnt/beta-catenin signaling and hair regrowth.

Note that CXXC5 is overexpressed in men with androgenetic alopecia (aka male pattern baldness). CXXC5 is a negative feedback regulator of the Wnt/beta-catenin pathway.