Miller School Researchers Collaborate in Use of Cancer Drug for Spinal Cord Repair
A team of Miller School of Medicine researchers, collaborating with investigators at other institutions, has demonstrated that the cancer drug epothilone promotes regeneration and locomotor recovery following spinal cord injury in adult rats. The research was recently published in Science.
“Epothilone offers a novel and exciting new possibility for spinal cord repair,” said Mary Bartlett Bunge, Ph.D., Christine E. Lynn Distinguished Professor in Neuroscience, and professor of cell biology, neurological surgery and neurology. “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.”
Bunge’s research colleagues at The Miami Project to Cure Paralysis were John Bixby, Ph.D., Vice Provost for Research and professor of molecular and cellular pharmacology, and neurological surgery; Michael Norenberg, M.D., Director of Neuropathology and professor of pathology, biochemistry and molecular biology, neurology and neurosurgery; and Miami Project Electron Microscopy Core Manager Margaret Bates.
One of the main barriers to regeneration in the damaged spinal cord is the formation of scar tissue in and around the injury site. The research demonstrates 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. Another important development noted by the researchers was improvement in walking.
Epothilone has the ability to cross the blood-brain barrier, which makes it less invasive because it can be introduced systemically instead of through a surgical procedure. The researchers achieved the first effective treatment in animal models with a microtubule stabilizer that can be delivered systemically.
The Miami Project’s extensive bank of injured human spinal cord tissue was key to the study. Special efforts were made to achieve extremely good preservation of the samples taken from tissue donors. The Electron Microscopy Core’s expertise was then put to use searching the stained samples for the presence of microtubules in retraction bulbs.
The research also demonstrated how Miller School and Miami Project investigators play an important role as teachers and mentors to the next generation of neuroscientists. Lead author Joerg Ruschel, now at the German Center for Neurodegenerative Diseases in Bonn, Germany, learned the injury model and performed experiments using local delivery of epothilone while a visiting student in Bixby’s laboratory several years ago.