Neuronal regeneration to restore hand and arm functions after paralysis

Cervical spinal cord injury (SCI) impairs hand and arm functions and carries with it devastating consequences in quality of life for affected individuals. Electrical stimulation of the spinal cord, in combination with rehabilitative training, improves hand and arm functions following cervical SCI, but is insufficient to fully restore functions. An eventual cure for SCI will therefore require biological repair strategies to promote axon growth through or around lesions. We recently leveraged our developmentally inspired regenerative gene therapy to restore walking after paralysis due to anatomically complete thoracic SCI. This therapy consists of 1) reactivation of dormant developmental growth programs in neurons above the injury, 2) production of axon growth permissive substrates within the core of the injury, and 3) chemoattraction to guide regrowing axons to their natural target region below the injury. We are now applying the same principles to target cervical SCI in mice. Initial results demonstrate that applying these principles to cervical SCI enables axon growth past SCI lesions and to natural target regions below the injury. Our goal is to regrow the axons of cervical propriospinal neurons past incomplete SCI lesions to promote biological repair and restoration of hand and arm functions in rodents, before assessing our gene therapy in non-human primates.