University of Florida researchers have received a $2.3 million grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health, to investigate strategies to treat muscle wasting and weakness caused by pancreatic cancer.
Andrew Judge, Ph.D., a UF Health Cancer Center member and professor in the department of physical therapy in the College of Public Health & Health Professions, is collaborating on the project with co-principal investigator Carl Atkinson, Ph.D., professor in the division of pulmonary, critical care & sleep medicine in the College of Medicine, and co-investigator Sarah Judge, Ph.D., a Cancer Center member and research assistant professor in the department of physical therapy.
The project will focus on unraveling the mechanisms of a condition called cachexia, which is characterized by progressive skeletal muscle and body weight loss and affects up to 80% of patients with cancer. When patients with cancer lose muscle mass and body weight, it can cause distressing changes to their physical appearance and make patients weak and fatigued. As a result, everyday activities can become monumental tasks. Cachexia can also change the cancer treatment plan and/or tolerance to treatments, decreasing both quality and length of life. There are currently no effective treatments, making it important to understand the underlying mechanisms so that such treatments can be developed.
Andrew Judge’s lab recently found that the complement system is associated with the development of cachexia in both mice and people with pancreatic cancer. The complement system is part of the body’s innate immune system.
“Our lab has been studying cellular mechanisms that are causative in cancer cachexia for more than a decade,” Judge said. “Our early work focused exclusively on preclinical models, but in more recent years, through ongoing collaborations with clinical colleagues here at UF and beyond, we have dedicated a significant amount of time to exploring the skeletal muscle phenotypes and molecular mediators linked to cachexia in pancreatic cancer patients. These studies are what led to the identification of the complement system as a potential driver of cancer-induced muscle atrophy and weakness.”
Recently, the lab has found that whole body deletion of complement component C3, which is the convergent point for all complement cascades, protects against pancreatic cancer-induced muscle atrophy and weakness in preclinical models. However, systemic inhibition of complement in diseases where local complement activity is the major concern is not without risk.
In the current project, the team will build on these findings by using mouse models to first identify the specific complement system activation and effector pathways involved and then to test targeted complement therapeutics to these specific pathways.
“The goal of the current work is to pinpoint the specific arm(s) of the complement cascade that are causative in cancer-induced muscle atrophy and weakness and then target those arms locally,” Judge said. “Although there are currently no effective treatments for cancer cachexia, the field is making significant progress. We believe this project has great potential because it was guided by findings in patients themselves, pre-establishing the clinical significance.”