Case Number 112005 - Appetite Stimulating Proteins

Contact: Jill Uhl
Phone: 513-558-5621

Description:  Dr. Glenn Millhauser and his lab at the University of California, Santa Cruz (UCSC) in collaboration with Dr. Stephen Benoit at the University of Cincinnati have discovered a group of proteins that will ultimately be of value in treating extreme cases of eating disorders such as anorexia or cachexia.

The agouti-related protein (AgRP) is produced in the brain and is a potent appetite stimulant. The normal 50 amino acid polypeptide is produced in the hypothalamus and binds with high affinity to the melanocortin 3 and 4 receptors (MC3R and MC4R). Along with alpha-melanocyte stimulating hormone (apha-MSH) and neuropeptide Y, AgRP plays a central role in the regulation of mammalian feeding and metabolism. From intracerebroventricular (ICV) injection studies, AgRP is well documented to enhance feeding for one to two days following a single injection, and is probably longer acting than any other known hormone or drug.

UCSC researchers have previously isolated the specific region of AgRP that is required to bind to the MC receptors. New studies show regions adjacent to those that make receptor contact are rich with positive charges, and while they do not influence receptor affinity, they’re critical for AgRP's long acting activity. UCSC researchers have now designed non-natural proteins where they’ve selectively enhanced certain charge characteristics and are able to greatly extend the time over which a single AgRP injection stimulates feeding. Normally, from ICV injections in rats, AgRP stimulates feeding over a 24 - 72 hour period, one to three days. UCSC researchers show that the newly designed protein stimulates feeding for six days. Moreover, the cumulative food intake stimulated by UCSC’s designed AgRP is approximately double that of control over the lifetime of the experiment. The animals increase their body weight by 15% in a one week period, compared to 5% in animals treated with wild type AgRP.

A patent is pending.

More technical information can be found in this article: Agouti-Related Protein Segments Outside of the Receptor Binding Core Are Required for Enhanced Short- and Long-term Feeding Stimulation.

More information can also be found through UCSC's Office for Management of Intellectual Property here.