New tools to activate and silence neural circuits (2012-2014)

Many human neurological disorders are caused by aberrant levels of neuronal activity. We have engineered a new receptor for controlling this activity in humans. This receptor is based on a minimally mutated human 1 glycine receptor chloride channel that incorporates a mutation that renders it highly sensitive to activation by the FDA-approved antiparasitic drug, ivermectin. Our plan is to express this construct in spinal motor neurons and activate it via oral delivery of ivermectin. Its advantages over existing methods include its human origin and ability to be activated by a safe orally administered drug. We aim to improve this receptor and validate it as a potential treatment for neurological disorders such as motor neuron disease.