• English
  • Español


Drug combination analysis is getting relevance in many fields such as agriculture, cancer research, and aging studies. Some of the challenges when performing these kinds of experiments are the experimental design and number of samples to test to perform a string dose-response combinatorial analysis.

Dr. Gonzalo Suarez, Ignacio Alcántara and Gustavo Salinas from Universidad de la República and Institut Pasteur de Montevideo, Uruguay, has recently reported (2022) one of the first anthelmintic drug-drug interaction study in C. elegans, applying WMicrotracker technology as a readout (Front. Pharmacol. 13:984905. doi: 10.3389/fphar.2022.984905)

Here we describe some of the main advantages of using C. elegans as an animal model for drug combination and the use of 96 well plates as a convenient format.

A successful case of WMicrotracker ONE application for combinational toxicology analysis and its complementation with WMicrotracker SMART

Caenorhabditis elegans is a free-living nematode that has been validated for anthelmintic drug screening. However, this model has not been used to address anthelmintic dose-response-time and drug-drug interactions through matrix array methodology. In Dr. Suarez’s study, they assessed the pharmacodynamics and drug-drug interactions of two anthelmintic drugs Eprinomectin (EPM) and Ivermectin (IVM). Since the action of these drugs causes worm paralysis, the infrared motility assay WMicrotracker ONE has been used to measure EPM and IVM effects on worm movement over time.

The results showed that EPM was slightly more potent than IVM, that drug potency increased with drug time exposure, and that once paralyzed, worms did not recover. Different EPM/IVM concentration ratios were used and synergy and combination sensitivity scores were determined at different exposure times, applying Highest Single Agent (HSA), Loewe additivity, Bliss and Zero Interaction Potency (ZIP) models. The acquired data allowed to perform 3D Isobologram Analysis to characterize Synergy SCORE (Figure 1).

Figure1. 3D surface of Synergy Scores for EPM and IVM drug-drug interaction. For all models, EPM and IVM interaction landscapes are shown in 3D (A). Highest Single Agent model (HAS) (B). Bliss Independence model (BLISS) (C). Loewe model (LOEWE) (D). Zero Interaction Potency model (ZIP). 90 min exposure time is shown in all cases. The mean value of Synergy Score is indicated in the SD surface (p value compared to 0% inhibition). No significant synergy (red) or antagonism (green) between EPM and IVM at all concentrations.Front. Pharmacol. 13:984905

Beyond Toxicology Quantification: Advancing Phenotypic Characterization Using the WMicrotracker SMART Imaging System

During our conversation with the author, Suárez provided insights into the mode of action of various anthelmintics and the differential killing of worms in terms of kinetics and observed phenotypes. Currently, he is employing advanced imaging techniques, including WMicrotracker SMART experiments, to gain a deeper understanding of the combinatorial effects of drugs and determine which drugs prevail in each interaction study.

Figure 2 displays graphical tracks of a population of worms exposed to Levamisole 100uM. WMicrotracker SMART software was utilized to generate a Z-Stack image from a 5-minute recording. Source: Phylumtech.

In line with this research direction, Phylumtech is actively collaborating with Suárez to enhance the throughput capability of the SMART system (Figure 2) for multi-plate reading. This development will provide a convenient methodology for analyzing dozens of plates per day.

We eagerly anticipate the forthcoming revelation of Suarez´s results and the valuable insights they will offer.


About the author:

Gonzalo Suárez is a researcher from Universidad de la Republica, Uruguay, and associated professor of the Faculty of Pharmacology UDELAR. His studies have been specialized on PKPD, Bioavailability, Bioequivalence and Veterinary Chemical disposal treatment, by using diverse animal models.