Noor Ul Ain, Armaan Saith, Audrey Ruan, Ruhua Yang, Aaron Burton, Pramod K Mistry
{"title":"Eliglustat substrate reduction therapy in children with Gaucher disease type 1.","authors":"Noor Ul Ain, Armaan Saith, Audrey Ruan, Ruhua Yang, Aaron Burton, Pramod K Mistry","doi":"10.3389/fped.2025.1543136","DOIUrl":null,"url":null,"abstract":"<p><strong>Importance: </strong>Gaucher disease (GD) is a rare lysosomal storage disorder with limited treatment options for pediatric patients. Oral substrate reduction therapy (SRT) with eliglustat offers a potential alternative, particularly for those with barriers to enzyme replacement therapy (ERT).</p><p><strong>Objective: </strong>Evaluate the safety and efficacy of eliglustat SRT in pediatric patients with type 1 Gaucher disease (GD1), both as initial therapy and as a switch from intravenous ERT.</p><p><strong>Design: </strong>A prospective case series was conducted from 2017 to 2024.</p><p><strong>Setting: </strong>Yale's National Gaucher Disease Treatment Center, New Haven, CT, United States.</p><p><strong>Participants: </strong>Fourteen pediatric GD1 patients with significant barriers to receiving ERT.</p><p><strong>Intervention: </strong>Eliglustat SRT was dosed pharmacogenomically based on CYP2D6 metabolizer status.</p><p><strong>Primary outcomes and measures: </strong>Primary outcomes included safety and efficacy in reversing indicators of disease activity. Secondary outcomes involved changes in patient and parent-reported quality of life, assessed using PROMIS questionnaires.</p><p><strong>Results: </strong>Eliglustat was initiated at a mean age of 12.5 years (range: 6-17 years) and administered for a mean duration of 3.6 years (range: 1-7 years). All patients remained on treatment and exhibited sustained reductions in glucosylsphingosine (GlcSph) levels compared to baseline (<i>p</i> = 0.005). Other disease indicators demonstrated corresponding improvements. Adverse effects were limited to transient gastroesophageal reflux in 3/14 patients (21%). Serial electrocardiograms (EKGs) were normal. Growth and developmental milestones were appropriate for age in all patients. Patients and their parents reported a global improvement in quality of life.</p><p><strong>Conclusions: </strong>Eliglustat demonstrated significant clinical benefits in pediatric GD1 patients, as evidenced by reductions in GlcSph levels and other disease indicators. The therapy showed a favorable safety profile comparable to that observed in adults. These findings suggest eliglustat is a promising therapeutic option for pediatric GD1 patients, providing an effective alternative to ERT.</p>","PeriodicalId":12637,"journal":{"name":"Frontiers in Pediatrics","volume":"13 ","pages":"1543136"},"PeriodicalIF":2.1000,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903696/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Pediatrics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fped.2025.1543136","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"PEDIATRICS","Score":null,"Total":0}
Eliglustat substrate reduction therapy in children with Gaucher disease type 1.
Importance: Gaucher disease (GD) is a rare lysosomal storage disorder with limited treatment options for pediatric patients. Oral substrate reduction therapy (SRT) with eliglustat offers a potential alternative, particularly for those with barriers to enzyme replacement therapy (ERT).
Objective: Evaluate the safety and efficacy of eliglustat SRT in pediatric patients with type 1 Gaucher disease (GD1), both as initial therapy and as a switch from intravenous ERT.
Design: A prospective case series was conducted from 2017 to 2024.
Setting: Yale's National Gaucher Disease Treatment Center, New Haven, CT, United States.
Participants: Fourteen pediatric GD1 patients with significant barriers to receiving ERT.
Intervention: Eliglustat SRT was dosed pharmacogenomically based on CYP2D6 metabolizer status.
Primary outcomes and measures: Primary outcomes included safety and efficacy in reversing indicators of disease activity. Secondary outcomes involved changes in patient and parent-reported quality of life, assessed using PROMIS questionnaires.
Results: Eliglustat was initiated at a mean age of 12.5 years (range: 6-17 years) and administered for a mean duration of 3.6 years (range: 1-7 years). All patients remained on treatment and exhibited sustained reductions in glucosylsphingosine (GlcSph) levels compared to baseline (p = 0.005). Other disease indicators demonstrated corresponding improvements. Adverse effects were limited to transient gastroesophageal reflux in 3/14 patients (21%). Serial electrocardiograms (EKGs) were normal. Growth and developmental milestones were appropriate for age in all patients. Patients and their parents reported a global improvement in quality of life.
Conclusions: Eliglustat demonstrated significant clinical benefits in pediatric GD1 patients, as evidenced by reductions in GlcSph levels and other disease indicators. The therapy showed a favorable safety profile comparable to that observed in adults. These findings suggest eliglustat is a promising therapeutic option for pediatric GD1 patients, providing an effective alternative to ERT.
期刊介绍：
Frontiers in Pediatrics (Impact Factor 2.33) publishes rigorously peer-reviewed research broadly across the field, from basic to clinical research that meets ongoing challenges in pediatric patient care and child health. Field Chief Editors Arjan Te Pas at Leiden University and Michael L. Moritz at the Children''s Hospital of Pittsburgh are supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Pediatrics also features Research Topics, Frontiers special theme-focused issues managed by Guest Associate Editors, addressing important areas in pediatrics. In this fashion, Frontiers serves as an outlet to publish the broadest aspects of pediatrics in both basic and clinical research, including high-quality reviews, case reports, editorials and commentaries related to all aspects of pediatrics.
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