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Production and Characterization of a Recombinant Alpha--acetyl Glucosaminidase Enzyme in the Yeast by Heidy Johana Triana; Oscar Fernando Sánchez; Carlos Javier Alméciga-Diaz; Angela Johana Espejo-Mojica is a Medicine article available to read on EtoBox.

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transcytosis of transferrin, to reach the brain parenchyma. Biodistribution and pharmacodynamics of JR-441 were evaluated in mice and monkeys. Delivery to CNS and peripheral tissues was examined by immunochemical methods and HS concentrations in these tissues were determined by a validated LC-MS/MS method. After a single intravenous administration, JR-441 was detected in the brain as well as in peripheral tissues of the hTfR-knock-in mice. Distribution of the drug to the brain was also confirmed in cynomolgus monkeys after a single intravenous dose. Immunohistochemical analysis showed that JR-441 was delivered to neuronal cells. We then evaluated the efficacy of repetitive intravenous administration of JR-441 in the reduction of accumulated HS in CNS and peripheral tissues of hTfR-knockin/Sgsh-knockout mice, an animal model of MPS IIIA. JR-441 markedly reduced HS concentrations in both CNS and peripheral tissues. These results demonstrate that the anti-hTfR antibody-fused SGSH penetrates to the brain by crossing the BBB and reduces the accumulated substrate when administered intravenously, and thereby suggest that JR-441 has the potential to exert therapeutic benefit on the CNS seq

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Author

Heidy Johana Triana; Oscar Fernando Sánchez; Carlos Javier Alméciga-Diaz; Angela Johana Espejo-Mojica

Publisher

Elsevier BV

Published

2021

Language

EN

Field

Medicine (Health Sciences)