Dentistry & Oral Surgery, Medical Research Institute KITANO HOSPITAL, PIIF Tazuke-kofukai, Osaka, Japan; Toregem Toregem BioPharma, Co.,Ltd, Kyoto, Japan.
Toregem Toregem BioPharma, Co.,Ltd, Kyoto, Japan.
J Oral Biosci. 2024 Dec;66(4):1-9. doi: 10.1016/j.job.2024.10.002. Epub 2024 Oct 9.
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).
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.
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.
本研究旨在开发一种促进自体组织牙齿再生的治疗剂，用于治疗先天性牙齿缺失，特别是先天性缺牙（≤5 颗缺失牙，患病率 10%）和少牙（≥6 颗缺失牙，患病率 0.1%）。
我们研究了 USAG-1 蛋白基因缺失的小鼠，该蛋白是 BMP/Wnt 的拮抗剂，可形成过多的牙齿。我们将 USAG-1 鉴定为增加牙齿数量的靶分子。将 USAG-1 缺陷小鼠与先天性牙齿缺失模型杂交可恢复牙齿形成。我们产生了抗 USAG-1 的中和抗体作为治疗先天性牙齿缺失的潜在治疗剂。小鼠抗 USAG-1 的中和抗体可能有潜力拯救发育停滞的牙胚，使其程序化形成特定类型的牙齿。一种人源化的抗 USAG-1 抗体已被开发为最终候选药物。
针对 USAG-1 具有治疗缺失的先天性牙齿的潜力。已经开发出抗 USAG-1 的中和抗体，并将推进临床试验，这可能会在先天性缺牙和少牙等情况下再生缺失的先天性牙齿。已完成 1 期研究的方案框架制定，正在为未来的研究做准备。
