ADHESION MOLECULE-1 TO ENHANCE DELIVERY OF THERAPEUTIC ENZYMES FOR TREATMENT OF LYSOSOMAL STORAGE DISEASES

Lysosomal storage diseases (LSDs) are a group of more than 40 genetically inherited diseases that result from dysfunction of specific proteins, often an enzyme, located in lysosomes within cells which leads to abnormal lysosomal accumulation of specific macromolecules. As a result, cell malfunction occurs and escalates into multi-tissue and multi-organ failures, often resulting in premature death. For several early onset LSDs, the central nervous system (CNS) is also affected and manifests fatal neuropathic and/or neurodegenerative symptoms. Within the last two decades, treatment for selective LSDs has become clinically available. Specifically, enzyme replacement therapy (ERT) by intravenous injection of recombinant enzymes holds relevant promise. Yet current ERT results in suboptimal enzyme biodistribution to many target organs, including the peripheral organs and also the CNS. Delivery to the CNS is particularly impeded due to the tight blood-brain barrier (BBB) that strictly regulates passage between the circulation system and the brain tissue. We explored the use of targeted drug delivery systems to address this issue. Specifically, we focused on targeting intercellular adhesion molecule-1 (ICAM-1), a cell surfac