Associate Professor of Anesthesia, Critical Care & Pain Medicine, and Neurology
Massachusetts General Hospital and Harvard Medical School
Associate Member, Broad Institute of MIT and Harvard
Justine Brown, MD
Associate Professor of Neurosurgery, Harvard Medical School
Spinal Motor Neuron Transplantation to Enhance Reconstruction Strategies Following Traumatic Nervous System Injury
Restoring function following peripheral nerve and spinal cord trauma is exceptionally challenging. While the peripheral nervous system does have some regenerative capability, the central nervous system is often irreversibly damaged following traumatic injury. Surgeons have developed nerve transfers as a method to reassign nerves that are still working after injury to control critical muscles. Patients can learn to control these muscles and gain function, but some critical muscle groups are not amenable to this strategy, as they are too far away (distal) from the site of injury, and oncoming regenerating nerves are too slow to reach the muscle before atrophy becomes permanent. A valuable tool in the surgeon’s arsenal is to use a nerve to “babysit” the distal muscle group until the regenerating nerve arrives. However, available nerves are scarce in these significant injuries.
With Stepping Strong Center funding, Wainger’s team proposes the use of motor neurons derived from induced pluripotent stem cells to provide support to distal muscles in a logical extension of the “babysitter” concept. In the past, motor neurons have been used in rodent models to preserve and activate muscles. Now, stem cells from human sources can be reliably turned into motor neurons to preserve muscles.
This research addresses key limitations to the clinical introduction of cell therapy. By providing the optimal dose of motor neurons to effectively innervate and preserve muscle, and with optimized parameters, this preservation leads to better nerve transfers in an injury animal model. Successful completion of this project establishes essential parameters for this and other stem cell therapies, creates a path to clinical introduction, and opens the door for more advanced rehabilitation and prosthetic technology.
Brian Wainger, MD, PhD, is an associate professor in anesthesiology and neurology at Harvard Medical School and an attending physician at Massachusetts General Hospital. He studied molecular biology as an undergraduate at Princeton University and ion channel physiology in the MD/PhD program at Columbia University. He then completed a medical residency in the Mass General Brigham Neurology Program followed by a clinical fellowship in Pain Medicine at MGH; a research fellowship with Clifford Woolf at Boston Children’s Hospital; and clinical investigator training through the Harvard master’s program in clinical and translational investigation. His clinical expertise spans the intersection of neurology and pain medicine.