Research & Economic Development

Office of the Vice Chancellor


IGF2R Specific Peptide Ligands for Liver Fibrosis

Need:

Liver Fibrosis is caused by chronic diseases such as hepatitis, liver cirrhosis caused by alcohol abuse and nonalcoholic steatohepatitis or fatty liver disease.  The prevalence of liver fibrosis is ever-increasing and effects approximately 30 million people in the United States alone.  Over 11% of people with liver fibrosis will progress to the more severe condition of cirrhosis, in which the liver begins to decompensate and lose overall function. The fibrotic stage is considered a key inflection point where baseline liver function can still be salvaged with adequate treatment. However, no approved treatment exists that ameliorates or reverses the course of fibrosis. 

Invention Details:

Liver Fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) in the liver. Hepatic stellate cells (HSCs) are responsible for the excessive production of ECM in a fibrotic liver.  A protein found on the surface of HSCs is insulin-like growth factor 2 receptor (IGFR2), which is upregulated in HSCs during liver fibrogenesis.  One of the major functions of IGFR2 is to internalize extracellular ligands; therefore IGFR2 could be used as a delivery system for small molecules into HSCs.

The proposed invention is an IGF2R-binding peptide identified by protein-based and whole-cell-based phage display with high binding affinity and target specificity. The proposed peptide (a.a. sequence - VHWDFRQWWQPS) exhibits high binding affinity and specificity toward IGF2R.  The peptide acts via two distinct mechanisms of action, 1) it acts as a carrier to deliver conjugated small molecule agents to HSCs; and 2) it acts as a targeting ligand for nanoparticles encapsulating antifibrotic agents.

Advantages:

Conventional methods for delivering drugs to HSCs have limitations, including inefficient uptake.  IGF2R is ubiquitously expressed on HSCs and facilitates entry of extracellular molecules at a relatively rapid rate.  Identifying peptide ligands that target IGF2R and bind with high affinity is imperative to the development of a HSC-targeted drug delivery system.  The identification of the IGF2R-specific peptide can be used to develop targeted therapeutics or imaging agents for liver fibrosis.

Suggested Uses:

To treat liver fibrosis as well as other diseases in which IGF2R plays an important role.

Patent Pending


IGF2R Peptide Ligands