Developmental Neurotoxicity

What is DNT?

Developmental neurotoxicity (DNT) testing is an important part of product safety assessments, looking at their potential effects on the developing nervous system. Conventional DNT assays mostly use mammalian models, which are time-consuming and costly. Moreover, many jurisdictions including in Europe and North America are phasing out animal testing in approvals of new chemical entities.

Alternatively, in vitro cell based assays with cultured neurons or microphysiological systems can be used. However, these in vitro systems do not represent a complete, developed, connected nervous system and lack anatomical structure and full animal physiology. They are also still relatively expensive and complicated to maintain.

Our unique approach

vivoVerse’s solution to this challenge is to use the well-studied nematode model organism C. elegans as a cost effective, rapid alternative in vivo model. Like rodent models, C. elegans has a fully characterized developmental timeline and a complete nervous system, including all the major neurotransmitter cell types found in humans e.g., dopamine, GABA, acetylcholine, and serotonin. Unlike rodent models, C. elegans develops from hatched larvae to mature adult in <3 days, has an easily studied transparent body, and is not subject to any welfare regulations.

Our DNT assay measures multiple neurodegeneration phenotypes to indicate potential adverse outcomes in exposed organisms. We treat populations of age synchronized C. elegans with one or more doses of the substances of interest and allow them to develop and show relevant phenotypes. Using our proprietary automated imaging platform and rapid GUI based image analysis pipeline, we can image and quantify these phenotypes in thousands of C. elegans to provide multi-parametric dose response assessments from large numbers of treated animals in weeks, not months.

What we can provide

  • Customized assay parameters e.g. number of chemicals, doses, strains
  • Quantification of multiple DNT relevant neurodegeneration phenotypes such as neuronal blebbing and deformation
  • Comparisons of the relative effect of multiple individual chemicals and their mixtures on DART endpoints, for lead candidate prioritization or demonstrating safety profile improvement over alternatives
  • Effective concentration and LOAEL values for multiple endpoints using dose curves
  • Behavioural endpoints such as animal movement speed and food uptake

Key benefits

  • Better value for money: Multiparametric in vivo endpoints quantified for a lower cost than a single acute toxicity study in mouse
  • Rapid results: A typical assay can be performed in as little as 6 weeks versus several months to >1 year for mammalian studies
  • Comparable results to mammalian models: C. elegans has ~83% homology with the human proteome and shows high concordance with toxicology results from mammals (~89% with rats in most chemical spaces for developmental toxicity).
  • Ethically compatible: We use an alternative model organism not subject to animal welfare regulations
  • Expert guidance: An experienced multi-disciplinary team with expertise in assay design and toxicology to help design your study

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