Therapeutic antibody for anorexia nervosa Abstract Anorexia nervosa (AN) is a psychiatric condition characterized by changes in eating habits eventually leading to weight loss of more than 15% and up to 85% in comparison to a healthy population. The natural course is variable, and long-term mortality is one of the highest of any psychiatric disorder. Treatment relies on nutritional and psychotherapy, and no specific drug treatment has been identified for AN. Growth differentiation factor 15 (GDF15) is well documented as a critical mediator of body weight loss, and high GDF15 levels are associated with AN. Administration of GDF15 causes weight loss in mice, rats, and primates. We have identified a high- affinity human monoclonal antibody that neutralizes GDF15 in animal models of tumor-associated cachexia. During this Phase 1 project, we will demonstrate activity of this antibody in murine models of AN. Phase 2 studies will advance preclinical testing, including pharmacokinetics and toxicology, in preparation for an IND. The therapeutic antibody to be developed in this project will directly block a major cause of weight loss to improve quality of life in AN patients.