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E1. A method of testing or determining in vivo
acute neurotoxicity of a molecule comprising measuring calcium oscillations in vitro
in neuronal cells which are in contact with the molecule.
The present disclosure provides a method of testing or determining
in vivo acute neurotoxicity of a molecule comprising measuring oscillations in intracellular free calcium concentration (“calcium oscillations”) in vitro in neuronal
cells which are in contact with the molecule.
The present methods can also improve efficiency (i.e.,
shorten) the evaluation period of candidate molecules by reducing the
screening time period for selection of molecules that do not
exhibit in vivo acute neurotoxicity. The present disclosure provides methods for testing
or determining the toxicity (e.g., in vivo acute neurotoxicity) of
a molecule by measuring certain characteristics of
the molecule. The present invention relates to methods for
selecting therapeutic molecules that have reduced toxic side
effects. In yet other embodiments, a therapeutic molecule of the invention binds to a molecule which is
useful in treating a neurological disease or disorder.
The above methods of the present invention can further comprise measuring tubulin intensity in a culture of neuronal cells, expression of a target protein,
or behavioral performance of the molecule. The present disclosure also
provides methods for selecting a molecule having reduced toxic side effects.
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