rexresearch1
Dr. Katsu TAKAHASHI
USAG-1 Protein Tooth Regeneration
USAG-1 Protein Tooth Regeneration
https://www.youtube.com/watch?v=6FXVyV3l0I0
Regrow Your Teeth | The End of Dental Implants // Medical Miracle
Led by Dr. Katsu Takahashi at Kitano Hospital (Osaka) in collaboration with Kyoto University, this groundbreaking research targets the USAG-1 protein that normally prevents additional tooth development. By blocking this "biological stop sign," dormant tooth buds can be reactivated to grow fully functional natural teeth.
https://newatlas.com/medical/tooth-regrowing-human-trial/
World-first tooth-regrowing drug will be given to humans in September
https://newatlas.com/medical/humans-grow-new-teeth-drug-trial/?itm_source=newatlas&itm_medium=article-body
Humans may soon grow new teeth, with promising drug trial set
...In an earlier study, the researchers landed on an antibody for uterine sensitization-associated gene-1 (USAG-1), which could stimulate new tooth growth in mice with tooth agenesis.
Essentially, the scientists found that USAG-1 interacts with other proteins to suppress tooth growth. Blocking the interaction can lead to bone morphogenetic protein (BMP) signaling, which triggers new tooth growth.
https://pubmed.ncbi.nlm.nih.gov/32922570/
Development of tooth regenerative medicine strategies by controlling the number of teeth using targeted molecular therapy
Katsu Takahashi 1 , et al.
Abstract -- Analysis of various genetically modified mice, with supernumerary teeth, has revealed the following two intrinsic molecular mechanisms that increase the number of teeth. One plausible explanation for supernumerary tooth formation is the rescue of tooth rudiments. Topical application of candidate molecules could lead to whole tooth formation under suitable conditions. Congenital tooth agenesis is caused by the cessation of tooth development due to the deletion of the causative gene and suppression of its function. The arrest of tooth development in Runx2 knockout mice, a mouse model of congenital tooth agenesis, is rescued in double knockout mice of Runx2 and Usag-1. The Usag-1 knockout mouse is a supernumerary model mouse. Targeted molecular therapy could be used to generate teeth in patients with congenital tooth agenesis by stimulating arrested tooth germs. The third dentition begins to develop when the second successional lamina is formed from the developing permanent tooth in humans and usually regresses apoptotically. Targeted molecular therapy, therefore, seems to be a suitable approach in whole-tooth regeneration by the stimulation of the third dentition. A second mechanism of supernumerary teeth formation involves the contribution of odontogenic epithelial stem cells in adults. Cebpb has been shown to be involved in maintaining the stemness of odontogenic epithelial stem cells and suppressing epithelial-mesenchymal transition. Odontogenic epithelial stem cells are differentiated from one of the tissue stem cells, enamel epithelial stem cells, and odontogenic mesenchymal cells are formed from odontogenic epithelial cells by epithelial-mesenchymal transition. Both odontogenic epithelial cells and odontogenic mesenchymal cells required to form teeth from enamel epithelial stem cells were directly induced to form excess teeth in adults. An approach for the development of targeted therapeutics has been the local application of monoclonal neutralizing antibody/siRNA with cationic gelatin for USAG-1 or small molecule for Cebpb.
https://pubmed.ncbi.nlm.nih.gov/39389160/
Development of a new antibody drug to treat congenital tooth agenesis // K Takahashi, et al.
Abstract -- Background: This study aimed to develop a therapeutic agent promoting teeth regeneration from autologous tissues for congenital tooth agenesis, specifically for hypodontia (?5 missing congenital teeth, 10% prevalence) and oligodontia (?6 missing congenital teeth, 0.1% prevalence).
Highlight: We studied mice genetically deficient in the USAG-1 protein, an antagonist of BMP/Wnt which forms excessive teeth. We identified USAG-1 as a target molecule for increasing the number of teeth. Crossing USAG-1-deficient mice with a congenital tooth agenesis model restored tooth formation. We produced anti-USAG-1 neutralizing antibodies as potential therapeutic agents for the treatment of congenital tooth agenesis. Mice anti-USAG-1 neutralizing antibodies can potentially rescue the developmentally arrested tooth germ programmed to a certain tooth type. A humanized anti-USAG-1 antibody was developed as the final candidate.
Conclusion: Targeting USAG-1 shows promise for treating missing congenital tooth. Anti-USAG-1 neutralizing antibodies have been developed and will progress towards clinical trials, which may regenerate missing congenital teeth in conditions, such as hypodontia and oligodontia. The protocol framework for a phase 1 study has been finalized, and preparation for future studies is underway.
https://pubmed.ncbi.nlm.nih.gov/39389160/
J Oral Biosci. 2024 Dec;66(4):1-9.
doi: 10.1016/j.job.2024.10.002. Epub 2024 Oct 9.
Development of a new antibody drug to treat congenital tooth agenesis
K Takahashi, et al.
Abstract
Background: This study aimed to develop a therapeutic agent promoting teeth regeneration from autologous tissues for congenital tooth agenesis, specifically for hypodontia (≤5 missing congenital teeth, 10% prevalence) and oligodontia (≥6 missing congenital teeth, 0.1% prevalence).
Highlight: We studied mice genetically deficient in the USAG-1 protein, an antagonist of BMP/Wnt which forms excessive teeth. We identified USAG-1 as a target molecule for increasing the number of teeth. Crossing USAG-1-deficient mice with a congenital tooth agenesis model restored tooth formation. We produced anti-USAG-1 neutralizing antibodies as potential therapeutic agents for the treatment of congenital tooth agenesis. Mice anti-USAG-1 neutralizing antibodies can potentially rescue the developmentally arrested tooth germ programmed to a certain tooth type. A humanized anti-USAG-1 antibody was developed as the final candidate.
Conclusion: Targeting USAG-1 shows promise for treating missing congenital tooth. Anti-USAG-1 neutralizing antibodies have been developed and will progress towards clinical trials, which may regenerate missing congenital teeth in conditions, such as hypodontia and oligodontia. The protocol framework for a phase 1 study has been finalized, and preparation for future studies is underway.
https://toregem.co.jp/en/
Toregem BioPharma
For the realization of a society where people are not afraid of losing their teeth
We are developing a regenerative treatment for tooth defects called “teething medicine”. We are working for the people who are genetically incapable of growing teeth or who have lost their teeth for some reason will regain their “own teeth”. We will contribute to the extension of people's healthy life span by developing and promoting innovative technologies that will enable them to continue chewing with their own teeth forever.
USAG-1 MOLECULE-TARGETING NEUTRALIZING ANTIBODY FOR TOOTH REGENERATION TREATMENT
US2025136674 (A1)
[ PDF ]
Provided are: an antibody which specifically binds to and neutralizes USAG-1 or an antigen-binding fragment thereof; and a pharmaceutical composition containing the antibody or the antigen-binding fragment.
Medicine Containing USAG-1-Targeting RNA Molecule for Tooth Regeneration Therapy
US2024043841
[ PDF ]
Provided is a medicinal composition to be topically administered for tooth regeneration therapy, said composition comprising an RNA molecule targeting USAG-1 or a nucleic acid molecule capable of yielding the RNA molecule and a pharmaceutically acceptable carrier.
Neutralizing Antibody for Tooth Regeneration Treatment Targeting USAG-1 Molecule
US2022259298
[ PDF ]
Provided are: an antibody which specifically binds to and neutralizes USAG-1 or an antigen-binding fragment thereof; and a pharmaceutical composition containing the antibody or the antigen-binding fragment.
IMPLANT BODY AND DENTAL IMPLANT
JP2023028834
[ PDF ]
To provide an implant body that can be favorably implanted above a newly growing tooth such as a permanent tooth and a regenerative tooth in an alveolar bone.SOLUTION: An implant body 130 is implanted above a newly growing tooth in an alveolar bone. The implant body 130 includes, on an upper part 131, an abutment 120 integrally formed therewith or the abutment 120 fixed thereto. At least a part of a lower part 132 of the implant body 130 is formed of a bioabsorbable material such that with the growth of the newly developing tooth, the implant body 130 becomes shorter from the tip thereof.