The 3Ns of Preclinical Animal Models in Biomedical Research

Vela, José Miguel; Maldonado, Rafaël; Hamon, Michel

doi:10.1002/9783527679348.ch01

Cited by 1 publication

(1 citation statement)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, as with other animal models, there are limitations and drawbacks in the zebrafish model [17,198,210]. The main one is inherent to its ability as a model of drugresistant epilepsies: the potential of zebrafish to identify novel more effective drugs remains to be proven.…”

Section: Asmmentioning

confidence: 99%

Animal Models of Drug-Resistant Epilepsy as Tools for Deciphering the Cellular and Molecular Mechanisms of Pharmacoresistance and Discovering More Effective Treatments

Löscher

White

2023

Cells

View full text Add to dashboard Cite

In the last 30 years, over 20 new anti-seizure medicines (ASMs) have been introduced into the market for the treatment of epilepsy using well-established preclinical seizure and epilepsy models. Despite this success, approximately 20–30% of patients with epilepsy have drug-resistant epilepsy (DRE). The current approach to ASM discovery for DRE relies largely on drug testing in various preclinical model systems that display varying degrees of ASM drug resistance. In recent years, attempts have been made to include more etiologically relevant models in the preclinical evaluation of a new investigational drug. Such models have played an important role in advancing a greater understanding of DRE at a mechanistic level and for hypothesis testing as new experimental evidence becomes available. This review provides a critical discussion of the pharmacology of models of adult focal epilepsy that allow for the selection of ASM responders and nonresponders and those models that display a pharmacoresistance per se to two or more ASMs. In addition, the pharmacology of animal models of major genetic epilepsies is discussed. Importantly, in addition to testing chemical compounds, several of the models discussed here can be used to evaluate other potential therapies for epilepsy such as neurostimulation, dietary treatments, gene therapy, or cell transplantation. This review also discusses the challenges associated with identifying novel therapies in the absence of a greater understanding of the mechanisms that contribute to DRE. Finally, this review discusses the lessons learned from the profile of the recently approved highly efficacious and broad-spectrum ASM cenobamate.

show abstract

Section: Asmmentioning

confidence: 99%