Search and Neutralize Factors (Cspgs) that Induce Decline in Transmission to Motoneurons from Spared Fibers after Chronic Spinal Cord Injury.

摘要

During the 3-years of Grant period plus 6-month no-cost extension we have accomplished all specific aims of the proposal and published six papers in highly rated scientific Journals. Briefly, we have conducted single-cell electrophysiological examination of individual CSPGs, i.e. inhibitory molecules which levels are up-regulated around glial scar after SCI. These experiments identified that NG2, but not other CSPGs, blocked axonal conduction. Then we demonstrated that monoclonal NG2-Antibody delivered via osmotic mini-pump can neutralize NG2-induced blockade of axonal conduction, in addition to improving axonal regeneration after SCI. As a result, SCI animals that received treatment with NG2-Ab secreted from minipump exhibited improved transmission and retrograde transport of anatomical tracer; this was associated with improved locomotor function revealed by a battery of behavioral tests. Moreover, in order to deliver NG2-Ab in less invasive method, during the last stage of the Proposal we have created the entirely novel construct, AAV-NG2-Ab, for AAV viral vector-based transgene delivery of NG2-Ab. Current experiments prove that this could be novel and effective gene therapy for SCI.