FXR agonists for MASH therapy: Lessons and perspectives from obeticholic acid.
Med Res Rev
; 44(2): 568-586, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-37899676
ABSTRACT
Nonalcoholic fatty liver disease, also called metabolic dysfunction-associated steatotic liver disease, is the most common liver disease worldwide and has no approved pharmacotherapy. Due to its beneficial effects on metabolic regulation, inflammation suppression, cell death prevention, and fibrogenesis inhibition, farnesoid X receptor (FXR) is widely accepted as a promising therapeutic target for nonalcoholic steatosis (NASH) or called metabolic dysfunction-associated steatohepatitis (MASH). Many FXR agonists have been developed for NASH/MASH therapy. Obeticholic acid (OCA) is the pioneering frontrunner FXR agonist and the first demonstrating success in clinical trials. Unfortunately, OCA did not receive regulatory approval as a NASH pharmacotherapy because its moderate benefits did not outweigh its safety risks, which may cast a shadow over FXR-based drug development for NASH/MASH. This review summarizes the milestones in the development of OCA for NASH/MASH and discuss its limitations, including moderate hepatoprotection and the undesirable side effects of dyslipidemia, pruritus, cholelithiasis, and liver toxicity risk, in depth. More importantly, we provide perspectives on FXR-based therapy for NASH/MASH, hoping to support a successful bench-to-clinic transition.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Hepatopatia Gordurosa não Alcoólica
Limite:
Humans
Idioma:
En
Revista:
Med Res Rev
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China