Restoring breathing function
Inhale. Exhale. Whether we’re awake or asleep, breathing is a function that rarely gets a second thought. But when there’s a break in the respiratory system’s circuit, say with a spinal cord injury, breathing may not be so natural.
David Fuller, Ph.D., is studying how the nervous system and respiratory muscles control breathing in the hope that his research may lead to treatments that restore respiratory function damaged by disease or injury, and reduce patients’ respiratory problems or even dependence on ventilators.
Spinal cord injury can break the connection between the cells in the brainstem responsible for respiratory rhythm and the neurons in the spinal cord that control the respiratory muscles, like the diaphragm.
“Any injury or disconnection between the brainstem and the spinal cord can cause a big problem with breathing because the brainstem can’t tell the respiratory muscles to contract and the muscles become weakened or paralyzed,” said Fuller, an associate professor in the department of physical therapy.
Fuller’s work draws on the concept of neuroplasticity — the brain and spinal cord’s ability to adopt new functions or reorganize existing ones. In the case of spinal cord injury, that could mean helping the nervous system create a new pathway so the brainstem can continue to send signals to respiratory muscles, or increasing the effectiveness of existing pathways.
Fuller and co-investigators Paul Reier, Ph.D., a professor in the College of Medicine’s department of neuroscience, and Heather Ross, Ph.D., a research assistant professor in the department of physical therapy, are currently conducting cell transplantation studies in laboratory rats aimed at repairing damaged respiratory circuits. They are working on promising approaches to this problem, including transplanting stem cells to replace or enhance the cells damaged by spinal cord injury. In another set of studies, they are grafting cells that produce the neurochemical serotonin, which can make neurons more active and improve the circuit’s functioning.
“Scientists have been transplanting cells into the spinal cord for 20 or 30 years so that’s not particularly new, but we’re trying to understand how we can recreate a circuit once a cell has been taken from one source and put into the spinal cord. Just having transplanted cells there might not help,” said Fuller, who also leads studies to determine if rehabilitation can enhance the connections between transplanted cells and the spinal cord.
In another study, Fuller and collaborator Barry Byrne, M.D., Ph.D., the director of UF’s Powell Gene Therapy Center, have done pioneering research on how the brain and the spinal cord influence breathing in patients with Pompe disease, a rare form of muscular dystrophy that causes severe respiratory problems. Their research in mice has helped lay the groundwork for the first gene therapy clinical trial for Pompe-related breathing problems. Byrne leads the study, which is currently being conducted with a group of children who have Pompe disease. Researchers hope the gene therapy will restore function in the patients’ respiratory muscles and nervous system.
“We don’t know the outcome, but this study has the potential to be a real translational success story because it is based on things that have been learned from basic science research,” Fuller said.