Recovery of forearm movement remains a largely unmet need for cervical spinal cord injury patients. We recently demonstrated that the drug 4-Aminopyridine (4-AP) is capable of raising significant levels of neural excitabilty from circuits that are spared after injury. Such enhancements in neural excitabilty through other drugs and therapies have been found to improve the odds of functional recovery when combined with motor training, the current standard of care for SCI patients. In this proposal, we seek to understand if combining 4-AP with motor training will produce lasting forearm function recovery. Past efforts to translate the potential of this promising drug have largely remained unsuccessful. We argue that the reason for this failure is due to lack of proper understanding of the neural circuits involved and the mechanisms of interactions when combining 4-AP and motor training. We propose to determine physiological and anatomical effects of combining 4-AP with motor training and test whether promoting excitability of forelimb circuits with this drug can potentiate the effects of motor training.
Our main goal is to optimally combine 4-AP and motor training to produce lasting motor recovery in arm and hand function. Our main objective is to identify which neural circuits are involved and understand the mechanisms of functional recovery when combining 4-AP with motor training.
The results from this proposal are poised to provide a new rationale for using an FDA-approved drug which is safe in people with SCI to potentiate the effects of motor training.