ZFIN ID: ZDB-PUB-190308-1
Screening drugs for myocardial disease in vivo with zebrafish: an expert update
Zhao, Y., Zhang, K., Sips, P., MacRae, C.A.
Date: 2019
Source: Expert opinion on drug discovery   14(4): 343-353 (Review)
Registered Authors: MacRae, Calum A.
Keywords: Zebrafish, cardiovascular, phenotype, screening
MeSH Terms:
  • Animals
  • Cardiomyopathies/drug therapy*
  • Cardiomyopathies/physiopathology
  • Cardiovascular Agents/administration & dosage
  • Cardiovascular Agents/pharmacology
  • Cardiovascular Diseases/drug therapy*
  • Cardiovascular Diseases/physiopathology
  • Disease Models, Animal
  • Drug Discovery/methods*
  • Drug Evaluation, Preclinical/methods
  • High-Throughput Screening Assays
  • Humans
  • Systems Biology/methods
  • Zebrafish
PubMed: 30836799 Full text @ Expert Opin. Drug Discov.
Our understanding of the complexity of cardiovascular disease pathophysiology remains very incomplete and has hampered cardiovascular drug development over recent decades. The prevalence of cardiovascular diseases and their increasing global burden call for novel strategies to address disease biology and drug discovery. Areas covered: This review describes the recent history of cardiovascular drug discovery using in vivo phenotype-based screening in zebrafish. The rationale for the use of this model is highlighted and the initial efforts in the fields of disease modeling and high-throughput screening are illustrated. Finally, the advantages and limitations of in vivo zebrafish screening are discussed, highlighting newer approaches, such as genome editing technologies, to accelerate our understanding of disease biology and the development of precise disease models. Expert opinion: Full understanding and faithful modeling of specific cardiovascular disease is a rate-limiting step for cardiovascular drug discovery. The resurgence of in vivo phenotype screening together with the advancement of systems biology approaches allows for the identification of lead compounds which show efficacy on integrative disease biology in the absence of validated targets. This strategy bypasses current gaps in knowledge of disease biology and paves the way for successful drug discovery and downstream molecular target identification.