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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Lim, H-H; Yi, H; Kishimoto, TK; Gao, F; Sun, B; Kishnani, PS

Published Date

  • December 2017

Published In

Volume / Issue

  • 13 /

Start / End Page

  • 18 - 22

PubMed ID

  • 28761815

Pubmed Central ID

  • 28761815

International Standard Serial Number (ISSN)

  • 2214-4269

Digital Object Identifier (DOI)

  • 10.1016/j.ymgmr.2017.03.005


  • eng

Conference Location

  • United States