Therapeutic antibody for anorexia nervosaAnorexia nervosa (AN) is a psychiatric condition characterized by changes in eating habits eventually leading toweight loss of more than 15% and up to 85% in comparison to a healthy population. The natural course isvariable, and long-term mortality is one of the highest of any psychiatric disorder. Treatment relies on nutritionaland 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 associatedwith 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 studieswill advance preclinical testing, including pharmacokinetics and toxicology, in preparation for an IND. Thetherapeutic antibody to be developed in this project will directly block a major cause of weight loss to improvequality of life in AN patients.
Public Health Relevance Statement: Narrative
Anorexia nervosa is a severe eating disorder leading to poor quality of life, with one of the highest mortality
rates of any psychiatric disorder. Treatment relies on nutritional modification and psychotherapy, and no specific
drugs are approved for AN. We have identified a monoclonal antibody that targets a pathway involved in appetite
and body weight homeostasis. During this study, we will evaluate this antibody in laboratory models of AN. With
further development, this treatment has the potential to be the first efficacious targeted therapeutic for AN.
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