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WARF: P130310US02

Non-Natural Peptides for Treating Diabetes


INVENTORS -

Samuel Gellman, Lisa Johnson, Alan Attie, Alan Saghatelian, Mark Keller

The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing peptide analogs of GLP-1 with prolonged effects in vivo.
OVERVIEWDiabetes mellitus continues to be a chronic public health issue despite the availability of injectable insulin since the 1920s. Finding alternative treatments is the subject of intense research. In recent years, efforts have focused on a potent anti-hyperglycemic hormone called glucagon-like peptide-1 (GLP-1).

GLP-1 is the natural agonist (activator) of a receptor found on the surface of pancreatic beta cells. Activation of this receptor promotes insulin release and survival of the beta cells. Such properties are attractive for treating type 2 diabetes. Unfortunately, GLP-1 is rapidly degraded by peptidase enzymes in the body. In fact, its half-life is less than two minutes.

There is interest in creating synthetic GLP-1 peptide analogs that resist degradation.
THE INVENTIONUW–Madison researchers have developed a new approach for designing GLP-1 receptor agonists that could be used to treat diabetes. The agonists retain GLP-1-like function but have prolonged activity in vivo.

The method includes strategically replacing native α-amino acid residues with conformationally constrained β-amino acid resides. The new α/β peptides mimic GLP-1 in terms of interacting with pancreatic beta cells and regulating blood glucose levels. The peptides are less susceptible to enzyme degradation due in part to the multiple β residue replacements.
BUSINESS OPPORTUNITY
  • Two GLP-1 receptor agonists have been approved for treating type 2 diabetes: exenatide (first patent expires in 2016) and liraglutide (patent expires in 2017).
APPLICATIONS
  • Non-natural peptides for potentially treating diabetes and hyperglycemia
KEY BENEFITS
  • Longer half-life in vivo than natural GLP-1
  • Glucose-lowering effects may compete with drugs currently on the market.
STAGE OF DEVELOPMENTThe researchers have assessed protease resistance in vitro, the effects of the peptide on glucose-dependent insulin secretion in cell culture, and performed a glucose tolerance test in mice.
Contact Information
For current licensing status, please contact Rafael Diaz at rdiaz@warf.org or (608) 265-9861.
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