Aruna Biomedical Inc., has been awarded more than $79,000 from the Environmental Protection Agency (EPA) Small Business Innovation Research (SBIR) program to study developmental neurotox assay using scalable neurons and astrocytes in high-content imaging.
The objective of this proposed project and the EPA Computational Toxicology program’s goals are aligned in assessing chemicals for potential risk to human health and the environment through the use of more representative multicellular human developmental neurotoxicology assays. ArunA Biomedical will develop a rapid, scalable, human pluripotent stem cell-derived cell-based coculture assay system to address a critical gap where animal developmental neurotoxicity testing for a single compound can be financially prohibitive (in excess of $1 million) and time consuming (up to 1.5 yrs). ArunA will manufacture pluripotent stem cell-derived neural cells using a patented system to generate functional neurons and astrocyte cultures, more closely mimicking the developing human nervous system than single cell-type assays.
In Phase I, object 1, ArunA will further refine a scalable and rapid means of generating enriched astrocytes form ArunA-based hNP1™ technology and cryopreserve them for use with hN2™ neurons, all within 48 hours post thaw. In objective 2 assays, specifically controlling the neuron to astrocyte ratio will occur, providing a flexible platform to more closely mimic ratios observed in the developing nervous system. In the last task, these co-cultures will be exposed to increasing doses of Pb acetate given its known effects on astrocytes and in light of EPA published direct effects on hN2™ neurons. The number of chemicals in the neurotoxicity training set will be increased in Phase II and contemporary comparisons made to commercial animal and human primary cell sources of neuron and astrocyte products to further validate ArunA’s developmental neurotoxicity assay.
The number of chemicals in the neurotoxicity training set will be increased in Phase II and contemporary comparisons made to commercial animal and human primary cell sources of neuron and astrocyte products to further validate ArunA’s developmental neurotoxicity assay. It is important to realize that primary sourced cells are good sources of cells for early studies; however, these cells are rarely scalable for throughput assays.
Finally, by employing adult sourced pluripotent stem cells (induced pluripotent cells) for more susceptible genetic and varied background in Phase II, we can develop products to help address a potential genetic influence on the developing human nervous system susceptibility to neurotoxicants.
After ArunA’s validated human neurite outgrowth assay is developed, the value and savings to industry and government will be significant because a validated assay service will augment or prioritize chemicals for expensive and time-consuming animal developmental neurotoxicity assays. We anticipate sales and services to exceed $10 million for near-term products and services developed through Phase I and Phase II funding and assay validation. In addition, validated assays performed by ArunA will drive the use of related assays, including, but not limited to, blood brain barrier assays and neural metabolomics studies. Toxicologists believe that complex tissue relevant, validated and informative human assays are needed in the foreseeable future (> 5 yrs) and ArunA will be responsive to current and future EPA needs and guidelines in this area.