vivoVerse is excited to announce it has been awarded a Phase I SBIR grant from the National Institute of Environmental Health Sciences (NIEHS) for the continued development of the company’s in vivo imaging and screening technologies.
Product safety profiling, of which developmental neurotoxicity (DNT) testing is an important component, is necessary to determine and continually ensure safe dosage or exposure levels of every chemical that comes into contact with humans. Toxicity testing is mostly done in genetically inbred mammals such as rats and rabbits, but public and regulatory pressure has led to directives eliminating the use of animals in safety testing where possible. vivoVerse is developing a DNT assay using a microscopic soil worm, C. elegans, to provide a faster, cheaper, and more ethical alternative to testing on mammals.
Animal testing is being replaced by New Approach Methodologies in many countries
Neurodevelopmental disorders such as ADHD, autism, and learning disabilities are on the rise globally. In the US, 1 in 6 children suffer from some form of developmental disability. One potentially important factor in their increase is exposure to chemicals of unknown toxicity in the environment. It is estimated that over a quarter of these cases may be caused partially or fully by chemical exposure. While there are over 350,000 chemicals in commercial uses and around 13,000 produced in large amounts, only a small percentage have toxicological data known. It is therefore vital to fully understand the risks of commonly encountered chemicals to minimize young people’s exposure to the most hazardous substances affecting sensitive developmental pathways.
These studies are prohibitively time consuming and expensive for testing the huge backlog of commercial chemicals, and may produce hard to interpret results due to the complexity of observed endpoints and differences between multiple laboratories. Additionally, many jurisdictions are limiting the numbers of animals that can be used for testing. New approach methodologies (NAMs) are a new paradigm in toxicology testing that bring together alternative approaches such as in in silico predictions, cell culture and microphysiological systems based assays, plus alternative model animals such as zebrafish, Drosophila and C. elegans.
The vivoChip-24x can immobilize ~1,000 animals in 24 different populations for high-resolution phenotypic imaging
vivoVerse will develop a comprehensive test battery for developmental neurotoxicity (DNT) utilizing the nematode model system, C. elegans. This battery will be able to assess the potential neurotoxic effects of various chemicals using a multiparametric approach tracking neuronal defects (neuronal loss, membrane beading, mislocalization etc.), synaptogenesis changes (missing or defective synapses), and behavioral changes (body bending and kinetics) over an animal’s development from late larval to early adult stage.
We propose to use C. elegans in a comprehensive DNT test battery where we will track neuronal, synaptic, and behavioral changes as the organism develops from late larval to adult stage after early exposure to DNT toxicants. We will develop novel reporter strains with fluorescent markers for GABAergic and dopaminergic neurons and synapses, expose them to reference chemicals and monitor the behavior of growing animals in culture before imaging them on our high-content microfluidic imaging platform at L4 and D1 stages. Specific behavioral endpoints will be analyzed by ML-based approaches from the behavioral videos. The high-resolution whole body 3D images from on-chip imaging will be analyzed by semi-automated methods for key DNT indicators such as neuronal loss and mislocalization, membrane blebbing, and defective or missing synapses. All these endpoints will be combined to find the dose of chemical at which the point of departure from the control occurs. Additionally, we plan to investigate potential modes of action using expression analysis of developmental and stress genes. Once our test battery is established, we will test a representative subset of chemicals from the DNT-DIVERS library to establish confidence in our model and lay the foundations for a fully automated low-cost, high-throughput DNT testing method to help assess the risks of common chemicals.
Growth and development of neurons and their synaptic connections can be affected by developmentally neurotoxic chemicals.
vivoVerse’s core focus is to facilitate the use of C. elegans as a model organism for life-science research and drug and toxicology screening through its innovative microfluidics-based platform. This platform allows researchers to rapidly immobilize thousands of microscopic animals for fast and high-resolution imaging within minutes. The high-density information and an automated image acquisition approach facilitate the quantification of different phenotypes caused by chemical exposures or disease-related mutations. Using high-content C. elegans screens, vivoVerse offers in vivo developmental and reproductive toxicology (DART) and developmental neurotoxicology (DNT) testing of chemicals in a dose-dependent manner.
vivoVerse’s in vivo toxicity services using the vivoChip® screening platform and C. elegans models will serve various industries including pharmaceutical, petrochemical, agricultural, cosmetics, and household consumer products. High-throughput toxicology screening services for new chemicals will be offered to commercial clients to identify any potential toxicity issues and accelerate the pathway to market for new products.
