Delivery System of Extracellular Matrix (ECM) Remodelers and their Inhibitors

Matrix-metalloproteinase 9 (MMP-9) is a secreted protease, which under dysregulated conditions leads to various pathologies. In the brain, MMP-9 mediates structural deformation of the extracellular matrix (ECM) and neuronal plasticity. This research focuses on the neurological disorder Fragile X syndrome (FXS) which is characterized by altered expression levels and proteolytic activity of MMP-9. To date, many drugs developed to cure brain pathologies face great challenges due to the blood-brain barrier (BBB) which tightly regulates the flow of all molecules entering the central nervous system. We use brain-targeted liposomal nanoparticles (NPs) also called neurosomes which are designed to deliver specific cargo to distinct areas in the brain. As a cargo, we utilize ECM modulators that were developed in the Sagi group and shown to impact the disease state. Here we present the first steps in designing and generating ECM remodeling brain-specific NPs.