Drs. Bunge and Bixby Research Demonstrates Positive Results for Spinal Cord Repair
March 2015 – Doctors John Bixby, Ph.D., Vice Provost for Research, Professor, Departments of Molecular & Cellular Pharmacology, Neurological Surgery and The Miami Project, Mary Bartlett Bunge, Ph.D., Christine E. Lynn Distinguished Professor in Neuroscience, Professor, Cell Biology, Neurological Surgery, Neurology and The Miami Project, Michael Norenberg, M.D., Director, Neuropathology, Professor, Department of Pathology, Biochemistry & Molecular Biology, Neurology, Neurosurgery, along with Miami Project Electron Microscopy Core Manager Margaret Bates were collaborators on a manuscript that was recently published in the prestigious journal Science. The paper demonstrates that the cancer drug, epothilone, promotes regeneration and locomotor recovery following spinal cord injury (SCI) in adult rats.
“Epothilone offers a novel and exciting new possibility for spinal cord repair—in one, non-invasive step scarring is reduced and axon growth and walking are improved. I would like to see more work in rat SCI models to test the combination of this agent with Schwann cells transplanted to fill the cavity that forms after contusive injury,” Mary B. Bunge.
One of the main barriers to regeneration in the damaged spinal cord is the formation of scar tissue in in and around the injury site. The paper shows that epothilone reduces the formation of this scar tissue by stabilizing microtubules, which form a scaffold-like structure within the cell, while at the same time promoting regeneration of neuron extensions in the injured spinal cord by fostering axonal growth. There also was an improvement in walking, which represents another positive development in gaining important knowledge in the field of SCI research.
Epothilone has the ability to cross the blood-brain barrier, which makes the administration of this intervention less invasive because it can be introduced systemically instead of through a surgical procedure. This is the first demonstration of an effective treatment in animal models with a microtubule stabilizer that can be delivered systemically.
The publication of this paper is another demonstration of Miller School and Miami Project researchers serving an important role as teachers and mentors to the next generation of neuroscientists. Lead author Joerg Ruschel, from the German Center for Neurodegenerative Diseases in Bonn, Germany, learned the injury model /from Dr. Caitlin Hill and performed experiments using local delivery of epothilone while he was a visiting student in the Lemmon-Bixby lab in Miami a few years ago.
Additionally, Dr. Bunge, Dr. Bixby, and Margaret Bates contributed to this paper by tapping into Miller School and Miami Project’s extensive injured human spinal cord tissue bank and providing electron microscopy expertise to search for microtubules in retraction bulbs in the injured spinal cord tissue from the bank. That the Electron Microscopy Core had made special arrangements to achieve especially good preservation of some injured human spinal cord made this contribution to the study possible. Dr. Norenberg identified and provided human spinal cord sections from a number of additional SCI tissue donors that could be stained for microtubules and retraction bulbs in the setting of chronic SCI.
Dr. Norenberg, along with Alex Marcillo M.D., oversees the human SCI tissue bank with The Miami Project. Through their continued work, the Miller School is able to provide this important resource to the SCI research field. Sections from the tissue bank are available to any scientists wishing to address specific research questions or to correlate human pathology to their laboratory findings. The tissue bank continues to provide a significant contribution to the development and appropriate targeting of interventions to repair the damaged spinal cord.