Researchers from Drexel University and the University of Miami Miller School of Medicine have discovered a new target for treating spinal cord injury.
In a recent study published in the Journal of Neuroscience, the scientists showed that the genetic deletion of a fatty acid receptor, CD36, improved motor function in mice. The genetic deletion appears to work by preventing inflammatory cells from ingesting myelin — the sheath that surrounds and protects nerve fibers.
“This study identifies a completely new way to potentially treat spinal cord injury,” said co-author Kara Spiller, PhD, an assistant professor at Drexel’s School of Biomedical Engineering, Science and Health Systems.
In the United States, about 300,000 people are living with spinal cord injuries, and there are about 17,000 new cases each year, according to the National Spinal Cord Injury Statistical Center.
The researchers were able to pinpoint the receptor by investigating the role of key immune system cells called macrophages, which are Spiller’s primary research focus. It has been well documented that, after a spinal cord injury breaks the body’s important blood-brain barrier, macrophages infiltrate the central nervous system, causing a cascade of pathological processes. It’s unclear exactly what macrophages may do that is beneficial or detrimental at this point. What is for sure, is that macrophage behavior can change rapidly depending on the cells’ environment.
To find out how macrophages influence injury, Yunjiao Zhu and Kirill Lyapichev, of the Miami Project to Cure Paralysis, first obtained macrophage-specific mRNA from injured spinal cords in mice, and then performed sequencing to investigate their transcriptional profile — a kind of log of their behavior. Those results showed that at seven days after injury, the most dramatic changes in macrophage gene expression pertained to lipid catabolism (the breaking down of fats and other similar materials).
Surprisingly, the molecular pathways of the macrophages were very similar to those described in foam cells, which are seen in atherosclerosis, or clogged arteries. They are formed when the body sends macrophages to the location of a fatty deposit on the blood vessel walls.
Spiller and her research team then analyzed the macrophage dataset in order to match their profile with other types of macrophages. Indeed, compared to 18 other types of macrophages, they saw that the cells’ gene expression most closely matched foam cells.
The research team hypothesized that macrophages transformed into foam cells, because they were actually absorbing the lipid-rich myelin coat that protects nerves in the central nervous system. So perhaps blocking the macrophages’ ability to ingest the myelin could help safeguard the spinal cord.
This is exactly what happened when University of Miami researchers used genetic tools to knock out the lipoprotein receptor CD36 in mice with spinal cord injuries. Once the macrophages were no longer able to consume the fatty myelin, the animals’ ability to move was improved 4 weeks after injury.
“However, the precise contribution of CD36 requires further investigation, since it has multiple ligands and is present in many different cell types,” said principal investigator Jae Lee, PhD, an associate professor at the University of Miami.
The results represent an exciting breakthrough in spinal cord injury research. According to Spiller, the researchers next hope to develop a drug that could target CD36 in human patients.
This study’s co-authors include John Bethea, PhD, a professor in the College of Arts and Sciences and Nicole Ferraro, a PhD candidate at Stanford University.
Spiller, Bethea and other Drexel faculty are pursuing similar lines of research as part of the new Drexel Neuroinflammation and Gender Research Program. The interdisciplinary collaboration is a product of the Drexel Areas of Research Excellence (DARE) awards and will investigate the biological basis of male/female differences in neuroinflammation and chronic pain.
For media inquiries, contact Lauren Ingeno at lingeno@drexel.edu or 215.895.2614.
