{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T08:13:14Z","timestamp":1777882394001,"version":"3.51.4"},"reference-count":63,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100015362","name":"Amicus Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015362","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Rare Disease"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:p>\n                    Late-onset Pompe disease (LOPD) is a rare inherited disorder caused by deficiency of the lysosomal enzyme acid \u03b1-glucosidase (GAA), leading to an accumulation of lysosomal glycogen in tissues, profoundly affecting muscles. Patients with LOPD typically have some residual GAA activity but experience progressive skeletal muscle dysfunction resulting in muscle weakness and respiratory failure. Enzyme replacement therapy (ERT) with alglucosidase alfa, a recombinant human GAA (rhGAA), was the first disease-specific therapy for Pompe disease. Despite efficacy in the first years of use, many patients receiving alglucosidase alfa experience a decline in function over time. This may reflect the inherent challenges associated with rhGAA ERT, such as enzyme inactivation at the near-neutral pH of blood, inefficient target cell uptake, and a necessity for complete lysosomal processing once inside target cells. Cipaglucosidase alfa, a second-generation rhGAA, aims to address these challenges through natural enrichment with bis-mannose-6-phosphate-containing\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    -glycans to enhance cellular uptake while retaining capacity for complete postdelivery processing. Co-administration of cipaglucosidase alfa with the small molecule stabilizer miglustat (N-butyldeoxynojirimycin) enhances cipaglucosidase alfa stability in the bloodstream after infusion. We discuss published and new preclinical and clinical data on the efficacy and safety of miglustat in combination with cipaglucosidase alfa for treating LOPD. Studies in Pompe mouse models and patients with Pompe disease showed that stabilization by miglustat improved cipaglucosidase alfa exposure and availability for uptake into target tissues and was associated with improved functional outcomes and biomarker levels compared with cipaglucosidase alfa alone. In patients with Pompe disease, the once every 2\u2009weeks dosing regimen of miglustat was well tolerated, with a low frequency of miglustat-related gastrointestinal events compared with daily miglustat regimens at higher doses used in the treatment of other diseases.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Trial registration<\/jats:italic>\n                      :\n                    <\/jats:bold>\n                    New data are reported for NCT02675465 (ATB200-02), NCT03729362 (PROPEL), and NCT04138277 (PROPEL open-label extension, ATB200-07); all registered at ClinicalTrials.gov (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\">https:\/\/clinicaltrials.gov<\/jats:ext-link>\n                    ).\n                  <\/jats:p>","DOI":"10.1177\/26330040261425686","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:44:27Z","timestamp":1772153067000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Miglustat: a first-in-class enzyme stabilizer for cipaglucosidase alfa for the treatment of late-onset Pompe disease"],"prefix":"10.1177","volume":"7","author":[{"given":"Robert J.","family":"Hopkin","sequence":"first","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics Cincinnati Children\u2019s Hospital Medical Center, College of Medicine, Cincinnati Children\u2019s Hospital, University of Cincinnati, Burnet Campus, 3333 Burnet Avenue, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry J.","family":"Byrne","sequence":"additional","affiliation":[{"name":"University of Florida, Gainesville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mazen M.","family":"Dimachkie","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priya S.","family":"Kishnani","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tahseen","family":"Mozaffar","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, Irvine, Irvine, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Roberts","sequence":"additional","affiliation":[{"name":"Salford Royal NHS Foundation Trust, Salford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedikt","family":"Schoser","sequence":"additional","affiliation":[{"name":"Friedrich-Baur-Institute, Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine A. M. E.","family":"van der Beek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ans T.","family":"van der Ploeg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Wenninger","sequence":"additional","affiliation":[{"name":"Friedrich-Baur-Institute, Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon","family":"Brudvig","sequence":"additional","affiliation":[{"name":"Amicus Therapeutics, Inc., Princeton, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Fox","sequence":"additional","affiliation":[{"name":"Amicus Therapeutics, Inc., Princeton, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred","family":"Holdbrook","sequence":"additional","affiliation":[{"name":"Amicus Therapeutics, Inc., Princeton, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vipul","family":"Jain","sequence":"additional","affiliation":[{"name":"Amicus Therapeutics, Inc., Princeton, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franklin","family":"Johnson","sequence":"additional","affiliation":[{"name":"Amicus Therapeutics, Inc., Princeton, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Zhang","sequence":"additional","affiliation":[{"name":"Amicus Therapeutics, Inc., Princeton, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giancarlo","family":"Parenti","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.2147\/ODRR.S69109"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2018.10.59"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.gim.0000218152.87434.f3"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.04.15"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2024.1451512"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.125358"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-021-10409-9"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12272"},{"key":"e_1_3_4_10_2","unstructured":"Amicus Therapeutics Inc. 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