Darpins: A New Generation of Protein Therapeutics in Neurodegenerative Diseases

Type of Award: catalyst
Award Number:
Award Period: February 2016 - January 2018
Amount Awarded: $ 200,000.00
PI(s): Raymond Roos, UChicago; Brian Kay, UIC;

Abstract: For many neurodegenerative diseases, antibodies have been used to knockdown cognate proteins that are thought to be pathogenic because they misfold and aggregate; however, antibodies have several shortcomings that limit their effectiveness. This proposal focuses on designed ankyrin repeat proteins (DARPins), which lack many of the shortcomings of antibodies. We recently generated DARPins against mutant (mt) SOD1, which is believed to misfold and cause 20% of cases of familial amyotrophic lateral sclerosis (FALS). We aim to characterize the DARPins and determine whether they prolong survival of ALS in mtSOD1 transgenic mice. We will also test whether mtSOD1 DARPins can react with the normal SOD1 in sporadic ALS, since recent data suggest that sporadic ALS involves abnormalities in the SOD1 protein similar to that seen with mtSOD1. Our studies may lead to new therapeutic directions in ALS and provide a proof of principle concerning the use of DARPins in neurodegenerative diseases.