Molecular Diagnostics and In Utero Therapeutics for Orofacial Clefts
| Autor: | Emma Turner, Leslie R Halpern, Shihai Jia, Jeremie D. Oliver, Rena N. D'Souza, Pascal Schneider |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cleft Lip Reviews Context (language use) Esthetics Dental Fibroblast growth factor Bioinformatics Bone morphogenetic protein 03 medical and health sciences 0302 clinical medicine Pregnancy Animals Humans Medicine Hedgehog Proteins Pathology Molecular Sonic hedgehog General Dentistry biology Palate business.industry Wnt signaling pathway Translational medicine Molecular diagnostics Cleft Lip/genetics Cleft Lip/surgery Cleft Palate/genetics Cleft Palate/surgery Female cleft palate craniofacial prenatal drug delivery replacement therapies signaling molecules translational medicine 3. Good health Cleft Palate 030104 developmental biology 030220 oncology & carcinogenesis biology.protein business Transforming growth factor |
| Zdroj: | J Dent Res Journal of dental research, vol. 99, no. 11, pp. 1221-1227 |
| ISSN: | 1544-0591 0022-0345 |
| DOI: | 10.1177/0022034520936245 |
| Popis: | Orofacial clefts and their management impose a substantial burden on patients, on their families, and on the health system. Under the current standard of care, affected patients are subjected to a lifelong journey of corrective surgeries and multidisciplinary management to replace bone and soft tissues, as well as restore esthetics and physiologic functions while restoring self-esteem and psychological health. Hence, a better understanding of the dynamic interplay of molecular signaling pathways at critical phases of palate development is necessary to pioneer novel prenatal interventions. Such pathways include transforming growth factor–β ( Tgfβ), sonic hedgehog ( Shh), wingless-integrated site ( Wnt)/β-catenin, bone morphogenetic protein ( Bmp), and fibroblast growth factor ( Fgf) and its associated receptors, among others. Here, we summarize commonly used surgical methods used to correct cleft defects postnatally. We also review the advances made in prenatal diagnostics of clefts through imaging and genomics and the various in utero surgical corrections that have been attempted thus far. An overview of how key mediators of signaling that drive palatogenesis are emphasized in the context of the framework and rationale for the development and testing of therapeutics in animal model systems and in humans is provided. The pros and cons of in utero therapies that can potentially restore molecular homeostasis needed for the proper growth and fusion of palatal shelves are presented. The theme advanced throughout this review is the need to develop preclinical molecular therapies that could ultimately be translated into human trials that can correct orofacial clefts at earlier stages of development. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|