A pilot study on using rapamycin-carrying synthetic vaccine particles (SVP) in conjunction with enzyme replacement therapy to induce immune tolerance in Pompe disease

dc.contributor.author

Lim, H-H

dc.contributor.author

Yi, H

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Kishimoto, TK

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Gao, F

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Sun, B

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Kishnani, PS

dc.date.accessioned

2017-07-24T16:30:32Z

dc.date.available

2017-07-24T16:30:32Z

dc.date.issued

2017-07-24

dc.description.abstract

A major obstacle to enzyme replacement therapy (ERT) with recombinant human acid-α-glucosidase (rhGAA) for Pompe disease is the development of high titers of anti-rhGAA antibodies in a subset of patients, which often leads to a loss of treatment efficacy. In an effort to induce sustained immune tolerance to rhGAA, we supplemented the rhGAA therapy with a weekly intravenous injection of synthetic vaccine particles carrying rapamycin (SVP-Rapa) during the first 3 weeks of a 12-week course of ERT in GAA-KO mice, and compared this with three intraperitoneal injections of methotrexate (MTX) per week for the first 3 weeks. Empty nanoparticles (NP) were used as negative control for SVP-Rapa. Co-administration of SVP-Rapa with rhGAA resulted in more durable inhibition of anti-rhGAA antibody responses, higher efficacy in glycogen clearance in skeletal muscles, and greater improvement of motor function than mice treated with empty NP or MTX. Body weight loss was observed during the MTX-treatment but not SVP-Rapa-treatment. Our data suggest that co-administration of SVP-Rapa may be an innovative and safe strategy to induce durable immune tolerance to rhGAA during the ERT in patients with Pompe disease, leading to improved clinical outcomes.

dc.identifier.issn

2214-4269

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https://hdl.handle.net/10161/15092

dc.language

English

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Elsevier BV

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Molecular Genetics and Metabolism Reports

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10.1016/j.ymgmr.2017.03.005

dc.subject

Pompe disease

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Acid alpha-glucosidase

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Enzyme replacement therapy

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Tolerogenic nanoparticles

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Rapamycin

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A pilot study on using rapamycin-carrying synthetic vaccine particles (SVP) in conjunction with enzyme replacement therapy to induce immune tolerance in Pompe disease

dc.type

Journal article

duke.contributor.orcid

Sun, B|0000-0002-2191-0025

duke.contributor.orcid

Kishnani, PS|0000-0001-8251-909X

pubs.begin-page

18

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22

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Clinical Science Departments

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Duke

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Pediatrics

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Pediatrics, Medical Genetics

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School of Medicine

pubs.publication-status

Published online

pubs.publisher-url

http://www.sciencedirect.com/science/article/pii/S2214426917300320

pubs.volume

13

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