IGF::OT::IGF-SCRIPPS RESEARCH INSTITUTE HHSN275201500006I HHSN275200001

Scripps Research Institute, The, La Jolla CA

Investigators

Abstract

This contract is to address the present and anticipated future needs of NIAAA?s Medication Development Program specific to the use of ghrelin vaccines. This contract will support the production, quality testing and shipping of ghrelin vaccines to NIH-supported investigators for research purposes. Ghrelin is a hormone predominantly secreted by endocrine cells in the stomach shown to stimulate hunger and eating, and as a key regulator of metabolism and energy homeostasis. Therefore, the ghrelin receptor has been pursued as a target for obesity medications. Further, recent studies have shown ghrelin to stimulate alcohol craving in alcohol dependent drinkers linking it to the desire to drink alcohol and alcohol dependence. In addition preclinical tests confirm that drugs acting upon the ghrelin receptor reduce alcohol reward and drinking. As a result, NIAAA clinical investigators are examining whether an orally administered ghrelin receptor antagonist, previously tested in humans for obesity, is safe for testing in alcohol dependent patients. Although small molecules targeting the ghrelin receptor have been examined in animals and humans, vaccines have until now only been proposed as a novel alternative for studying the role of ghrelin in feeding and obesity. It is now proposed that ghrelin vaccines may be a useful tool for investigating the role of ghrelin in alcohol craving, ingestion, and dependence. Antibodies to the ghrelin peptide affect its ghrelin-receptor mediated actions as well as other potential effects of ghrelin. They also eliminate potential off-target effects found in small molecules. Important to the possible development of ghrelin vaccines as a therapy for alcohol use disorder is that vaccine effects are long lasting and would eliminate the need for daily dosing and the associated issues concerning dosing regimen compliance. Establishing that ghrelin vaccines are an effective and safe method for reducing alcohol cravings in alcohol dependent subjects would be an important step in the discovery of medications for alcoholism. To achieve this aim, this task order will support the synthesis of ghrelin vaccines against rat hormone and distribute to NIH-supported investigators for research purposes.