Neural cell based assays derived from human ES cells

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DESCRIPTION (provided by applicant): Neurons send instructions to other cells in the form of electrical signals that allow movement, sensation, memory, learning and countless other activities that are taken for granted in daily life. Loss of neural cell function results from traumatic injuries such as gunshots wounds or car accidents and from neurodegenerative diseases. The scale of this health problem is virtually immeasurable: 4 million Americans alone are now diagnosed with Alzheimer's and another 500,000 with Parkinson's disease. Most neurons are produced during embryonic development by neural stem cells or neuroprogenitor cells. Biomedical researchers have derived neuroprogenitor cells from human embryonic stem cells (hESCs), providing a potential source of human neurons and glial cells for biomedical research through in vitro differentiation. Existing sources of human neuroprogenitors are propagated as suspensions of neurospheres that cannot be easily adapted for quantitative analysis or use in high-throughput or high-content screens for therapeutic compounds or for tests of neurotoxicity. Biomedical research to relieve the burden of neurological disorders is hampered by the lack of an adequate human neural cell-based model. Aruna Biomedical proposes to develop turn-key kits containing the needed reagents to propagate and reliably differentiate WA09 hESC (NIH registered) derived neuroprogenitors into primary cultures of neurons and glial cells. The potential technical innovation is the ability to proliferate and differentiate Aruna's neuroprogenitors in adherent monolayer cultures. The expected outcome is that researchers will have increased access to quantitative studies. In the Phase I portion of this Fast Track STTR project, human neuroprogenitors will be derived from WA09 hESCs. Immunochemical methods and flow cell cytometry will verify expansion into cultures that are s 90% pure and retain a normal diploid karyotype. To demonstrate proof of concept, neuroprogenitors will be differentiated in vitro and the yield of motor neurons in differentiated cell cultures will be established by confocal immunofluorescence microscopy, quantified in three trials, and tested with statistical methods. The results of Phase I studies will provide the groundwork for a Fast Track Phase II proposal to optimize methods for commercial production and to enhance the utility of neuroprogenitor cells and their derivatives by the end user. The vision of Aruna Biomedical is that commercialization of our products in Phase III will significantly advance the field by enhancing the ability of academic and commercial researchers to perform quantitative analysis with hESC derived neural cell-based assays.