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

Haney, Matthew J.; Zhao, Yuling; Jin, Yeon S.; Batrakova, Elena V.

doi:10.3390/cells9051273

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

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Center for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

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Cells 2020, 9(5), 1273; https://doi.org/10.3390/cells9051273

Received: 25 March 2020 / Revised: 14 May 2020 / Accepted: 19 May 2020 / Published: 20 May 2020

(This article belongs to the Special Issue Therapeutic Applications of Extracellular Vesicles)

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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 TPP1 accumulation in the brain, decreased neurodegeneration and neuroinflammation, and reduced aggregation of lysosomal storage material in BD mouse model, CLN2 knock-out mice. Parenteral intravenous and intraperitoneal administrations led to TPP1 delivery to peripheral organs: liver, kidney, spleen, and lungs. A combination of intrathecal and intraperitoneal EV-TPP1 injections significantly prolonged lifespan in BD mice. Overall, the optimization of treatment strategies is crucial for successful applications of EVs-based therapeutics for BD. View Full-Text

Keywords: Batten disease; brain bioavailability; drug delivery; extracellular vesicles; neuroinflammation

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Haney, M.J.; Zhao, Y.; Jin, Y.S.; Batrakova, E.V. Extracellular Vesicles as Drug Carriers for Enzyme Replacement Therapy to Treat CLN2 Batten Disease: Optimization of Drug Administration Routes. Cells 2020, 9, 1273. https://doi.org/10.3390/cells9051273

AMA Style

Haney MJ, Zhao Y, Jin YS, Batrakova EV. Extracellular Vesicles as Drug Carriers for Enzyme Replacement Therapy to Treat CLN2 Batten Disease: Optimization of Drug Administration Routes. Cells. 2020; 9(5):1273. https://doi.org/10.3390/cells9051273

Chicago/Turabian Style

Haney, Matthew J., Yuling Zhao, Yeon S. Jin, and Elena V. Batrakova. 2020. "Extracellular Vesicles as Drug Carriers for Enzyme Replacement Therapy to Treat CLN2 Batten Disease: Optimization of Drug Administration Routes" Cells 9, no. 5: 1273. https://doi.org/10.3390/cells9051273

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

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