Exalys Therapeutics has awarded Duke Anesthesiology’s Niccolò Terrando, PhD, a $200,479 grant for his project, “Test the Efficacy of Exalys EP4 Antagonist to Prevent Neuroinflammation and Delirium in a Preclinical Model.” The project will study the efficacy and safety of Exalys’ lead Prostaglandin E2 receptor 4 (EP4) antagonist in preventing cognitive decline (inattentiveness) and associated inflammatory biomarkers in a surgical preclinical model of delirium (orthopedic fracture). Results from this study could advance the development of a new immune-drug target to combat delirium. Terrando and Dr. Ting Yang of Duke Medicine serve as co-principal investigators.
Postoperative delirium, also referred to as “acute brain failure,” is a common and serious surgical complication in older patients that can lead to increased hospital costs and poor post-discharge outcomes. The ongoing pandemic due to COVID-19 has further highlighted the multiple challenges related to treating patients with delirium, especially given the limited therapeutic options available. Despite the prevalence of delirium in multiple settings, ranging from critical illness to elective surgical procedures, there are currently no therapies to possibly prevent delirium.
Delirium is a challenging, multifactorial pathology, with several mechanisms impacting the brain functioning of vulnerable patients. The Neuroinflammation and Cognitive Outcomes Laboratory, directed by Terrando at Duke Anesthesiology, has identified a critical role of systemic inflammation in driving “acute brain failure” and causing pathologic and behavioral changes in rodent models that resemble features of human delirium.
“Inflammation truly is a double edge sword in the setting of perioperative recovery,” says Terrando, associate professor in anesthesiology. “We know many of the deleterious effects that pro-inflammatory molecules can exert on the brain. We also know that blocking these molecules can impair the recovery of postoperative patients, for example by impairing healing.” Yang and Terrando recently contributed a review in Nature Immunology discussing the role of innate immunity in driving perioperative neurocognitive disorders, such as delirium.
“We are thrilled for the opportunity provided by Exalys to test and expand the potential application of this new compound to prevent delirium,” Yang adds. Her laboratory is actively studying the role of EP4 signaling in cardiovascular disorders, including hypertension and brain inflammation.