ZeEfficacy – Efficacy Services


ZeEfficacy: Getting the right insights

The ZeEfficacy platform is a portfolio of zebrafish solutions including ready-to-use disease models and high throughput phenotypic screening, for drug discovery and genetic functional studies.

Development of  new drugs costs >€2,5 bn and takes 10-15 years to complete. Preclinical development of compounds is a long and expensive process and represents 30% of the drug development cost. Huge failure rates are behind these high costs, as thousands of compounds are screened early in the R&D process, but only a few will ultimately receive approval. Optimization of the compound screening process using cost-efficient models and high performance approaches would have a major impact on reducing drug development costs.

Different preclinical strategies can be used to identify potential drug candidates. A study of approved drugs revealed that phenotypic screening has been more successful than others in the discovery of new drugs. Looking broadly back over the last decades, the phenotypic-based approaches have resulted in twice as many approved new drugs as target-centric assays.

Those insights indicate that Biopharmaceutical companies can benefit from expanding their phenotype-based drug discovery programs. By focusing on the phenotype, efficacious drugs are identified in a more cost- and time-efficient manner.

Phenotype-based approaches are particularly well suited for:

Compound Efficacy Evaluation

AIM: screening compounds to determine the functional efficacy ameliorating disease phenotypes.

Experimental steps:

  1. Dose range determination: determine test dosage through toxicity and solubility evaluations.
  2. Set up assays and models: genetically or pharmacologically reproduce disease state or condition in zebrafish. 
  3. Compound effects assessment: use a functional phenotype to generate data about compound efficacy.
  4. Data analysis: to reveal if candidate therapeutic compounds are effective, identifying those compounds that rescue the wild-type phenotype in a validated disease model.
Genetic Functional Studies 

AIM: to understand the biological functions of a gene in a given condition, for target validation.

Experimental steps:

  1. Model generation: stable genetic models can be generated by using CRISPR or other genome editing methods. Alternatively, transient genetic perturbations can be performed by using RNA downregulation and overexpression techniques.
  2. Phenotypic profiling: use functional phenotypes (e.g., behavioral, metabolic) and transcriptional analysis to generate data about the effect of the genetic modification. 
  3. Understand the mechanism of actions (MoA): analyzed data delivers information about molecular targets, biochemical pathways, and other MoAs.

Zebrafish, a highly informative model

The Zebrafish model has been revealed as a powerful in vivo system for modeling human diseases and drug discovery. Its advantages include: 

High homology: zebrafish have a similar genetic structure to humans.  More than 70% of human genes have a zebrafish orthologue gene. This percentage goes up to 82% if we only consider genes that are associated with human diseases.

High conservation: most zebrafish and human genes have a conserved function. As a result, most organs have a comparable histological organization and sustain the same function in the two species.

Biological translatability of pathological phenotypes to human disease biology. Zebrafish disease characteristics, etiology and progression, and molecular mechanisms are highly conserved and clinically relevant.

Our offerings

Custom Phenotyping

Our phenotypic characterization assays use zebrafish to bridge the gap between in vitro and murine models. Using this phenotype-based screening, drug discovery can be target-independent and whole organism outputs based from the beginning. This approach focuses on ameliorating phenotypes to discover efficacious compounds, ultimately accelerating and reducing the cost of identifying new drugs.

Phenotypic assays are also suited for the identification of disease-relevant genes (target validation), and for mechanism of action studies.

Our imaging and high throughput capabilities, plus our expertise in several therapeutic areas, allow us to offer a wide range of organ-specific analyses, which can be customized to suit your needs.

See more details about our custom phenotyping offerings:

Disease models

We are specialized in the generation of zebrafish disease models to be used in the early stages of drug discovery. You can take advantage of our ready-to-use models covering multiple research fields, or ask for your tailor-made disease model in a specific therapeutic area. 

Because genetic advances allow us to reliably express human proteins in zebrafish, these in vivo models are more translational than ever before. These humanized model systems can serve as efficient tools to study human diseases and to screen for potential therapeutic compounds.

Unlike cell-based platforms, zebrafish enables modeling a wider range of disease-associated phenotypes, and can better mimic the genetic heterogeneity of human patients, as well as the physiological outputs of human conditions.

Our ready-to-use zebrafish disease models include: