Abstract # 2080 The development of novel approaches for diagnostics and pre-clinical therapy for tauopathies using transport peptides for drugs and antibodies into the brain

Abstract

Delivery to the brain is a major challenge in central nervous system (CNS) drug development. The blood–brain barrier (BBB) prevents access of biotherapeutics to their targets in the CNS and therefore prohibit the effective treatment of neurological disorders. To find BBB-shuttle peptides that target to the brain, we performed a phage display method against a primary rat BBB cellular model which mimics the characteristics of the BBB. From the panning experiment of a 12-mer library, several novel peptide sequences were discovered and their permeability was evaluated. The permeability of peptides was measured by ultra-performance liquid chromatography – tandem mass spectrometry coupled to a triple-quadrupole mass spectrometer (UHPLC-MS/MS). Our results showed the importance of in vitro BBB model for the discovery of BBB- shuttle peptides through phage display libraries. The results indicate that the peptides identified by the in vitro phage selection approach could be useful transporters for systemically administrated biofarmaceuticals into the brain with therapeutic benefits.