Development of a new antibody drug to treat congenital tooth agenesis.
Congenital tooth agenesis
Tooth regeneration
USAG-1 neutralizing antibody
Wnt10A
Journal
Journal of oral biosciences
ISSN: 1880-3865
Titre abrégé: J Oral Biosci
Pays: Netherlands
ID NLM: 101226721
Informations de publication
Date de publication:
08 Oct 2024
08 Oct 2024
Historique:
received:
17
08
2024
revised:
04
10
2024
accepted:
07
10
2024
medline:
11
10
2024
pubmed:
11
10
2024
entrez:
10
10
2024
Statut:
aheadofprint
Résumé
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.
Sections du résumé
BACKGROUND
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
CONCLUSIONS
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
CONCLUSIONS
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.
Identifiants
pubmed: 39389160
pii: S1349-0079(24)00204-4
doi: 10.1016/j.job.2024.10.002
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024. Published by Elsevier B.V.