PTD-DBM 5mg

PTD-DBM is a hybrid polypeptide sequence that consists of two functional subunits: PTD and DBM. PTDs or Protein Transduction Domains are short polypeptide sequences capable of passing through the cell membrane and transporting certain macromolecules (that otherwise aren’t able to pass through on their own) into a cell. These macromolecules include proteins, sugars, nucleic acids, and active substances of certain medications. A common example of a PTD is a TAT peptide derived from the Trans-Activator of Transcription (TAT) of Human Immunodeficiency Virus (HIV).

DBMs or Dishevelled Binding Motifs are polypeptide sequences designed specifically to bind to the Dishevelled proteins (Dvl), which are crucial for the Wnt/beta-catenin signaling pathway. These motifs are usually found in certain proteins that interact with Dvl in order to influence the Wnt signaling. DBMs are often small and conserved sequences recognized by the binding domains of the Dvl proteins. After binding to them, DBMs influence the activation or inhibition of the Wnt/beta-catenin pathway. 

By combining a PTD and a DBM, we get a PTD-DBM, a polypeptide that has numerous beneficial qualities, such as cell proliferation, bone regeneration, and tissue-repairing abilities. 

PTD-DBM Research Benefits

PTD-DBM and Hair Follicles

The most notable benefit of this peptide is fighting hair loss by slowing down the shedding process of the existing hair follicles while stimulating the regrowth of the new hair follicles. PTD-DBM achieves this by blocking the binding of CXXC5 (CXXC-type zinc finger protein 5, an endogenous protein that is directly linked to hair loss) to the Dvl proteins. By doing so, PTD-DBM activates the Wnt/beta-catenin pathway. When applied topically, PTD-DBM has been shown to be highly effective for treating hair loss, significantly slowing down the shedding of the hair follicles while inducing a rapid growth of new ones. When used in combination with VPA (Valproic Acid, an agent that acts as an additional activator of the Wnt/beta-catenin pathway), PTD-DBM can induce the regrowth of hair follicles in the previously bald areas of the scalp.

Benefits Of Using PTD-DBM For Treating Hair Loss Compared To The Alternatives

 Ever since its discovery, PTD-DBM has shown multiple benefits, most notable being its cell proliferation and regeneration capabilities. As previously mentioned, by reducing the interactions between CXXC5 and Dvl proteins and, therefore, preventing them from binding, PTD-DBM activates the Wnt/beta-catenin pathway and thus enhances the overall cell activity. This particular property has shown to be revolutionary for treating hair loss, providing us with a completely new approach. By stimulating their cell activity, PTD-DBM is able to shift the hair follicles from the resting phase to the growth phase, which is highly beneficial for those suffering from conditions such as androgenic alopecia or telogen effluvium, both of which can present themselves with miniaturized or completely dormant hair follicles. After the stem cells of the hair follicles have been stimulated, they enter the state of anagen, a phase of the hair growth cycle when the activity of hair follicles is the highest. When in anagen, hair follicles produce thicker and longer hair.

The PTD component of PTD-DBM plays a crucial role in achieving its desired effects. Being able to precisely target desired cells and penetrate their membrane while carrying necessary proteins, PTD allows us a completely non-invasive approach, which is of great significance when dealing with delicate structures such as hair follicles. It has shown major advantages compared to the more invasive alternatives, such as hair transplant by surgically grafting individual follicles, and less effective drug delivery methods, such as oral medications or systematic treatments.

Another major benefit of using PTD-DBM for treating hair loss is its non-hormonal approach to hair regrowth. Compared to the more popular hormone-based alternatives such as minoxidil and finasteride, using PTD-DBM excludes the side effects of hormonal treatments, such as scalp irritation, sexual dysfunction, mood swings, and depression.

Current Research On PTD-DBM

Being a relatively new concept, PTD-DBM has been growingly researched in various areas of medical development for its remarkable cell activity stimulation and regeneration properties. These properties directly result from PTD-DBM blocking the binding of CXXC5 to the Dvl protein and its negative effects on the cell population with certain tissues where cells are densely grouped, such as skin or bones.

Research from 2015 has evaluated the negative effects of the CXXC5 on the skin healing capabilities and confirmed that using PTD-DBM to block it from binding to the Dvl is highly beneficial for the speed of wound healing and the overall regeneration rate of the skin cell population.

Another research from 2023 has demonstrated that the CXXC5 is a direct mediator of DHT-induced alopecia via PGD2, as well as the positive effect of PTD-DBM for hair regrowth. Dihydrotestosterone (DHT), an androgenic hormone that plays a crucial role in the sexual development of males, is greatly responsible for androgenetic alopecia, also known as male-pattern baldness. The whole process is carried out by the Prostaglandin D2 (PGD2), although its direct influence on the androgenetic alopecia is far less understood. This research has successfully shown the connection between the activity of CXXC5 and the PGD2 and their effect on the overall severity of DHT-induced hair loss. Simultaneously, a rapid hair regrowth was observed after the use of PTD-DBM, which directly blocks the activity of CXXC5 by activating the Wnt/beta-catenin pathway and, therefore, minimizing the negative effects of PGD2 as well.

Summary

PTD-DBM is a hybrid, artificial polypeptide used for manipulating cellular signaling pathways (Wnt/beta-catenin pathway in particular) and precisely delivering DBM to the target cells. Despite still being a developing concept that is yet to be widely commercialized and popularized, PTD-DBM has already shown so many positive effects on the overall metabolism and lifecycle of certain cell populations, most notable of them being the hair follicles. Therefore, it presents a revolutionary approach to the widespread issue of hair loss and its treatment. Extensive research has been done, and so far, the studies only affirm the positive effects of PTD-DBM on the quality of hair follicles, as well as its potential to improve the quality and quantity of other cell populations, such as skin and bone cells.

Resources:

•     Lee SH, Seo SH, Lee DH, Pi LQ, Lee WS, Choi KY. Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis. J Invest Dermatol. 2017 Nov;137(11):2260-2269. doi: 10.1016/j.jid.2017.04.038. Epub 2017 Jun 6. PMID: 28595998. https://pubmed.ncbi.nlm.nih.gov/28595998/
•     National Center for Biotechnology Information. "PubChem Substance Record for SID 476298902, PTD-DBM Acetate, Source: CreativePeptides" PubChem, https://pubchem.ncbi.nlm.nih.gov/substance/476298902. Accessed 3 May, 2024.
•     Ryu YC, Park J, Kim YR, Choi S, Kim GU, Kim E, Hwang Y, Kim H, Han G, Lee SH, Choi KY. CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD2. Cells. 2023 Feb 9;12(4):555. doi: 10.3390/cells12040555. PMID: 36831222; PMCID: PMC9954685.
•     Ryu YC, Lee DH, Shim J, Park J, Kim YR, Choi S, Bak SS, Sung YK, Lee SH, Choi KY. KY19382, a novel activator of Wnt/β-catenin signalling, promotes hair regrowth and hair follicle neogenesis. Br J Pharmacol. 2021 Jun;178(12):2533-2546. doi: 10.1111/bph.15438. Epub 2021 May 5. PMID: 33751552; PMCID: PMC8251890.
•     Hyun-Yi Kim, Sehee Choi, Ji-Hye Yoon, Hwan Jung Lim, Hyuk Lee, Jiwon Choi, Eun Ji Ro, Jung-Nyoung Heo, Weontae Lee, Kyoung Tai No, Kang-Yell Choi, Small molecule inhibitors of the Dishevelled-CXXC5 interaction are new drug candidates for bone anabolic osteoporosis therapy, EMBO Mol Med (2016)8:375-387. https://doi.org/10.15252/emmm.201505714
•     Choi S, Yoon M, Choi KY. Approaches for Regenerative Healing of Cutaneous Wound with an Emphasis on Strategies Activating the Wnt/β-Catenin Pathway. Adv Wound Care (New Rochelle). 2022 Feb;11(2):70-86. doi: 10.1089/wound.2020.1284. Epub 2021 Apr 20. PMID: 33573472; PMCID: PMC9831250.
•     Lee SH, Kim MY, Kim HY, Lee YM, Kim H, Nam KA, Roh MR, Min do S, Chung KY, Choi KY. The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing. J Exp Med. 2015 Jun 29;212(7):1061-80. doi: 10.1084/jem.20141601. Epub 2015 Jun 8. PMID: 26056233; PMCID: PMC4493411. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493411/