Extracellular Vesicles as Drug Carriers for Enzyme Replacement Therapy to Treat CLN2 Batten Disease: Optimization of Drug Administration Routes.

ABSTRACT: CLN2 Batten disease (BD) is one of a broad class of lysosomal storage disorders that is characterized by the deficiency of lysosomal enzyme, TPP1, resulting in a build-up of toxic intracellular storage material in all organs and subsequent damage. A major challenge for BD therapeutics is delivery of enzymatically active TPP1 to the brain to attenuate progressive loss of neurological functions. To accomplish this daunting task, we propose the harnessing of naturally occurring nanoparticles, extracellular vesicles (EVs). Herein, we incorporated TPP1 into EVs released by immune cells, macrophages, and examined biodistribution and therapeutic efficacy of EV-TPP1 in BD mouse model, using various routes of administration. Administration through intrathecal and intranasal routes resulted in high

SUBMITTER: Haney MJ 

PROVIDER: S-EPMC7290714 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature