Macrophage-Specific Drug Targets for Treating SCI
Abstract
Up to half a million people suffer a spinal cord injury (SCI) every year. The frequency of SCI is significantly higher in military Service Members. Statistics show that 4 out of every 100,000 Service Members sustained an SCI between the years 2005 and 2009. At present, there are no Food and Drug Administration-approved drugs that can effectively treat SCI. Reducing inflammation at the injury site is one of the most promising therapeutic strategies. Unfortunately, existing anti-inflammatory drugs have shown little benefit. While controlled inflammation is typically good for wound healing, the process persists chronically in SCI and results in irreversible damage to spinal cord tissue. We discovered that a type of immune cells, called macrophages, drive this inflammatory process in a manner that is specific to the SCI environment. Macrophages typically migrate to wounds and contribute to the healing process by engulfing contaminants and tissue debris. In the SCI site, they engulf a type of fat (or lipid) that typically coats healthy nerves, called myelin. This causes the macrophages to become laden with lipid droplets, giving them a foamy appearance. The foamy macrophages start to release signals that recruit additional macrophages to the site of injury, thereby triggering the vicious cycle of inflammation that persists chronically. Our goal is to identify specific components that can be targeted by novel drugs (or drug targets) to block the process of foamy macrophage formation and stymie the inflammatory process early on. The process of identifying drug targets is historically very difficult, and constitutes one of the biggest bottlenecks for the drug development process. To overcome this challenge, we will use to powerful technologies that we developed out our labs. The first one is an assay that uses macrophage cells exposed to myelin in the lab setting, which allows us to mimic the transformation of macrophages into the foamy state and dissect their behavior. The second is a biotechnology platform that uses machine learning to analyze the data obtained from the macrophage assay and identify novel drug targets for preventing foamy macrophage formation in SCI.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110940
Entities
People
- Jae Lee
Organizations
- United States Army
- University of Miami