Translating atherosclerosis research from bench to bedside: navigating the barriers for effective preclinical drug discovery

Lauren T. May, Belinda A. Bartolo, David G. Harrison, Tomasz Guzik, Grant R. Drummond, Gemma A. Figtree, Rebecca H. Ritchie, Kerry Anne Rye, Judy B. de Haan

Research output: Contribution to journalReview ArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Cardiovascular disease (CVD) remains the leading cause of death worldwide. An ongoing challenge remains the development of novel pharmacotherapies to treat CVD, particularly atherosclerosis. Effective mechanism-informed development and translation of new drugs requires a deep understanding of the known and currently unknown biological mechanisms underpinning atherosclerosis, accompanied by optimization of traditional drug discovery approaches. Current animal models do not precisely recapitulate the pathobiology underpinning human CVD. Accordingly, a fundamental limitation in early-stage drug discovery has been the lack of consensus regarding an appropriate experimental in vivo model that can mimic human atherosclerosis. However, when coupled with a clear understanding of the specific advantages and limitations of the model employed, preclinical animal models remain a crucial component for evaluating pharmacological interventions. Within this perspective, we will provide an overview of the mechanisms and modalities of atherosclerotic drugs, including those in the preclinical and early clinical development stage. Additionally, we highlight recent preclinical models that have improved our understanding of atherosclerosis and associated clinical consequences and propose model adaptations to facilitate the development of new and effective treatments.

Original languageEnglish
Pages (from-to)1731-1758
Number of pages28
JournalClinical Science
Volume136
Issue number23
DOIs
Publication statusPublished - 9 Dec 2022

Keywords

  • atherosclerosis
  • cardiovascular disease
  • coronary artery disease
  • drug discovery and design
  • model organisms

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