{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:13:32Z","timestamp":1785543212200,"version":"3.56.0"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T00:00:00Z","timestamp":1592524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:p>Gaucher\u2019s disease type 1 (GD1) leads to significant morbidity and mortality through clinical manifestations, such as splenomegaly, hematological complications, and bone disease. Two types of therapies are currently approved for GD1: enzyme replacement therapy (ERT), and substrate reduction therapy (SRT). In this study, we have developed a quantitative systems pharmacology (QSP) model, which recapitulates the effects of eliglustat, the only first\u2010line SRT approved for GD1, on treatment\u2010na\u00efve or patients with ERT\u2010stabilized adult GD1. This multiscale model represents the mechanism of action of eliglustat that leads toward reduction of spleen volume. Model capabilities were illustrated through the application of the model to predict ERT and eliglustat responses in virtual populations of adult patients with GD1, representing patients across a spectrum of disease severity as defined by genotype\u2010phenotype relationships. In summary, the QSP model provides a mechanistic computational platform for predicting treatment response via different modalities within the heterogeneous GD1 patient population.<\/jats:p>","DOI":"10.1002\/psp4.12506","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T11:40:13Z","timestamp":1592566813000},"page":"374-383","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["A Quantitative Systems Pharmacology Model of Gaucher Disease Type 1 Provides Mechanistic Insight Into the Response to Substrate Reduction Therapy With Eliglustat"],"prefix":"10.1002","volume":"9","author":[{"given":"Ruth","family":"Abrams","sequence":"first","affiliation":[{"name":"Translational Disease Modelling Digital Data Science Sanofi Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanchala D.","family":"Kaddi","sequence":"additional","affiliation":[{"name":"Translational Disease Modelling Digital Data Science Sanofi Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdi","family":"Tao","sequence":"additional","affiliation":[{"name":"Translational Disease Modelling Digital Data Science Sanofi Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randolph J.","family":"Leiser","sequence":"additional","affiliation":[{"name":"Translational Disease Modelling Digital Data Science Sanofi Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Simoni","sequence":"additional","affiliation":[{"name":"Fondazione The Microsoft Research \u2010 University of Trento Centre for Computational and Systems Biology (COSBI) Rovereto Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7891-5695","authenticated-orcid":false,"given":"Federico","family":"Reali","sequence":"additional","affiliation":[{"name":"Fondazione The Microsoft Research \u2010 University of Trento Centre for Computational and Systems Biology (COSBI) Rovereto Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Tolsma","sequence":"additional","affiliation":[{"name":"RES Group Inc Needham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Jasper","sequence":"additional","affiliation":[{"name":"RES Group Inc Needham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"van Rijn","sequence":"additional","affiliation":[{"name":"Translational Disease Modelling Digital Data Science Sanofi Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Translational Disease Modelling Digital Data Science Sanofi Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Niesner","sequence":"additional","affiliation":[{"name":"Translational Disease Modelling Digital Data Science Sanofi Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Barrett","sequence":"additional","affiliation":[{"name":"Translational Disease Modelling Digital Data Science Sanofi Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Marchetti","sequence":"additional","affiliation":[{"name":"Fondazione The Microsoft Research \u2010 University of Trento Centre for Computational and Systems Biology (COSBI) Rovereto Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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