Office of Technology Transfer – University of Michigan

Glucagon-like Peptide-1 Fusion Protein for Treating Diabetes and Cardiovascular Diseases

Technology #6539

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Categories
Researchers
Yuqing (Eugene) Chen
Managed By
Tiefei Dong
Senior Licensing Specialist, Life Sciences 734-763-5332
Publications
Glucagon-Like Peptide-1(9-37) Fusion Proteins Suppress Hepatic Gluconeogenesis in Zebrafish Larva and Mice
Canadian Journal of Diabetes. October 2014Volume 38, Issue 5, Supplement, Page S67, 2014
In vivo expression of GLP-1/IgG-Fc fusion protein enhances beta-cell mass and protects against streptozotocin-induced diabetes
Gene Ther. 2007 Jun;14(12):981-8. Epub 2007 Apr 5, 2007
Novel GLP-1 fusion chimera as potent long acting GLP-1 receptor agonist,
PLoS One. 2010 Sep 15;5(9):e12734. doi: 10.1371/journal.pone.0012734, 2010

The prevalence of type 2 diabetes is growing in the United States and around the world. The disease afflicts an estimated 504 million individuals globally, including 20.9 million Americans. Because of its characteristic insulin resistance, type 2 diabetes not only leads to short-term problems with glucose uptake, but it can also lead to long-term complications including other metabolic problems, cardiovascular disease, renal disease, loss of lower limb circulation/mobility, visual impairment, and eventually death. One culprit behind type 2 diabetes is the body’s reduced responsiveness to a hormone called glucagon-like peptide-1 (GLP-1), which normally stimulates insulin secretion. While GLP-1 treatment improves insulin secretion in studies of patients with type 2 diabetes, the short half-life of the active form of the hormone (less than 2 minutes) indicates that it is degraded rapidly, requiring continuous administration of high concentrations over the course of hours. To avoid the impracticalities of this strategy, a treatment that mimics the effects of the active form of GLP-1 but that remains intact longer would be highly desirable.

A metabolized variant of GLP-1 fused with an immunoglobulin increases insulin secretion and has cardiovascular protective effects

Recent research demonstrates that a breakdown product of the active form of GLP-1 holds promise as a potential treatment for type 2 diabetes. Because the product, which was originally thought to be an inactive form of GLP-1, is already broken down, it is less susceptible to degradation. It therefore lasts longer than the “active” form. When fused to an immunoglobulin, this GLP-1 variant is a potent stimulator of glucose-dependent insulin secretion in humans. Transgenic expression of this GLP-1/immunoglobulin fusion protein in mice increases serum insulin and enhances responsiveness to both glucose and insulin. As an added benefit, studies of the GLP-1 breakdown product have also shown cardiovascular protective effects in mouse models of either cardiac hypertrophy or myocardial infarction. Together, these data support the GLP-1/immunoglobulin fusion protein as a powerful potential treatment for both type 2 diabetes and cardiovascular disease.

Applications

  • Treatment for type 2 diabetes
  • Treatment for cardiovascular disease

Advantages

  • Stable
  • Long-lasting