Zebrafish larvae have evolved into a very attractive model for drug discovery. Recently published methods facilitate genetical engineering of zebrafish, allowing the study of targets of interest in an easily accessible vertebrate system: a multiorgan culture model. Zebrafish is being used in Roche research and early development for both safety and efficacy studies.
At Roche, we are excited about the zebrafish as an alternative model for supporting our '3R' efforts, the refinement, reduction and replacement of animal studies
Facts and figures: Zebrafish are
Genes and stripes
The Zebrafish has been defined as “science’s new supermodel,” and as befitting a supermodel, it has already made the cover of prestigious magazines, including Science, Nature, New Scientist and others of similar caliber. While it may have to work on its runway walk, it makes up for it with a unique combination of scope and relevance.
Zebrafish larvae can be bred in big numbers, are transparent, tiny and motionless. Very recently, a number of methods have been optimised that simplify the genetic engineering of these little fish, and allow them to express a variety of human and/or disease relevant genes in zebrafish larvae. Contrary to the fruit fly, Drosophila, and the worm, C. Elegans, which have been pivotal in our understanding of genes and phenotypes, zebrafish are vertebrates, and therefore much more relevant for human physiology in health and disease.
Roche is at the head of the class when it comes to the school of zebrafish research, and is pursuing the use of zebrafish in both safety and efficacy testing.
In vivo models
In Vivo Models are key components of the drug discovery value chain. Testing in living organisms is still the only way to fully evaluate the efficacy, pharmacology, pharmacokinetic and safety of a potential drug candidate before starting clinical studies in humans. Moreover, highly normed studies in living organisms are explicitly required by regulatory authorities all across the world to guarantee that no safety concerns exist for the healthy volunteers or the patients involved in the testing of a new therapeutic agent. At Roche, we strive to minimise the use of animal studies and gain the most relevant information from any study we conduct or any model we develop. We also strive to achieve the highest standard of animal welfare and to switch to non-invasive studies or substitute in vivo with in silico, in vitro or alternative models whenever possible. The zebrafish is an alternative in vivo model which is currently being evaluated at Roche to study the effects of compounds on target organ toxicities.