Trial of

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
01 Feb 2024
Historique:
medline: 31 1 2024
pubmed: 31 1 2024
entrez: 31 1 2024
Statut: ppublish

Résumé

Niemann-Pick disease type C is a rare lysosomal storage disorder. We evaluated the safety and efficacy of In this double-blind, placebo-controlled, crossover trial, we randomly assigned patients 4 years of age or older with genetically confirmed Niemann-Pick disease type C in a 1:1 ratio to receive NALL for 12 weeks, followed by placebo for 12 weeks, or to receive placebo for 12 weeks, followed by NALL for 12 weeks. NALL or matching placebo was administered orally two to three times per day, with patients 4 to 12 years of age receiving weight-based doses (2 to 4 g per day) and those 13 years of age or older receiving a dose of 4 g per day. The primary end point was the total score on the Scale for the Assessment and Rating of Ataxia (SARA; range, 0 to 40, with lower scores indicating better neurologic status). Secondary end points included scores on the Clinical Global Impression of Improvement, the Spinocerebellar Ataxia Functional Index, and the Modified Disability Rating Scale. Crossover data from the two 12-week periods in each group were included in the comparisons of NALL with placebo. A total of 60 patients 5 to 67 years of age were enrolled. The mean baseline SARA total scores used in the primary analysis were 15.88 before receipt of the first dose of NALL (60 patients) and 15.68 before receipt of the first dose of placebo (59 patients; 1 patient never received placebo). The mean (±SD) change from baseline in the SARA total score was -1.97±2.43 points after 12 weeks of receiving NALL and -0.60±2.39 points after 12 weeks of receiving placebo (least-squares mean difference, -1.28 points; 95% confidence interval, -1.91 to -0.65; P<0.001). The results for the secondary end points were generally supportive of the findings in the primary analysis, but these were not adjusted for multiple comparisons. The incidence of adverse events was similar with NALL and placebo, and no treatment-related serious adverse events occurred. Among patients with Niemann-Pick disease type C, treatment with NALL for 12 weeks led to better neurologic status than placebo. A longer period is needed to determine the long-term effects of this agent in patients with Niemann-Pick disease type C. (Funded by IntraBio; ClinicalTrials.gov number, NCT05163288; EudraCT number, 2021-005356-10.).

Sections du résumé

BACKGROUND BACKGROUND
Niemann-Pick disease type C is a rare lysosomal storage disorder. We evaluated the safety and efficacy of
METHODS METHODS
In this double-blind, placebo-controlled, crossover trial, we randomly assigned patients 4 years of age or older with genetically confirmed Niemann-Pick disease type C in a 1:1 ratio to receive NALL for 12 weeks, followed by placebo for 12 weeks, or to receive placebo for 12 weeks, followed by NALL for 12 weeks. NALL or matching placebo was administered orally two to three times per day, with patients 4 to 12 years of age receiving weight-based doses (2 to 4 g per day) and those 13 years of age or older receiving a dose of 4 g per day. The primary end point was the total score on the Scale for the Assessment and Rating of Ataxia (SARA; range, 0 to 40, with lower scores indicating better neurologic status). Secondary end points included scores on the Clinical Global Impression of Improvement, the Spinocerebellar Ataxia Functional Index, and the Modified Disability Rating Scale. Crossover data from the two 12-week periods in each group were included in the comparisons of NALL with placebo.
RESULTS RESULTS
A total of 60 patients 5 to 67 years of age were enrolled. The mean baseline SARA total scores used in the primary analysis were 15.88 before receipt of the first dose of NALL (60 patients) and 15.68 before receipt of the first dose of placebo (59 patients; 1 patient never received placebo). The mean (±SD) change from baseline in the SARA total score was -1.97±2.43 points after 12 weeks of receiving NALL and -0.60±2.39 points after 12 weeks of receiving placebo (least-squares mean difference, -1.28 points; 95% confidence interval, -1.91 to -0.65; P<0.001). The results for the secondary end points were generally supportive of the findings in the primary analysis, but these were not adjusted for multiple comparisons. The incidence of adverse events was similar with NALL and placebo, and no treatment-related serious adverse events occurred.
CONCLUSIONS CONCLUSIONS
Among patients with Niemann-Pick disease type C, treatment with NALL for 12 weeks led to better neurologic status than placebo. A longer period is needed to determine the long-term effects of this agent in patients with Niemann-Pick disease type C. (Funded by IntraBio; ClinicalTrials.gov number, NCT05163288; EudraCT number, 2021-005356-10.).

Identifiants

DOI: 10.1056/NEJMoa2310151 PMID: 38294974
pubmed: 38294974
doi: 10.1056/NEJMoa2310151
doi:

Banques de données

ClinicalTrials.gov
['NCT05163288']
EudraCT
['2021-005356-10']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

421-431

Informations de copyright

Copyright © 2024 Massachusetts Medical Society.

Auteurs

Tatiana Bremova-Ertl (T)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).
ORCID: 0000-0002-7397-045X

Uma Ramaswami (U)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).
ORCID: 0000-0002-4703-7447

Marion Brands (M)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).
ORCID: 0000-0002-2025-5997

Tomas Foltan (T)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).

Matthias Gautschi (M)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).
ORCID: 0000-0003-1358-1759

Paul Gissen (P)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).
ORCID: 0000-0002-9712-6122

Francesca Gowing (F)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).

Andreas Hahn (A)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).
ORCID: 0000-0001-9727-7580

Simon Jones (S)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).

Richard Kay (R)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).

Miriam Kolnikova (M)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).
ORCID: 0000-0002-9211-4456

Laila Arash-Kaps (L)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).

Thorsten Marquardt (T)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).
ORCID: 0000-0002-9982-2981

Eugen Mengel (E)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).
ORCID: 0000-0001-8967-2951

Julien H Park (JH)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).
ORCID: 0000-0003-2305-9948

Stella Reichmannová (S)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).
ORCID: 0000-0002-3719-8650

Susanne A Schneider (SA)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).
ORCID: 0000-0001-7283-1995

Siyamini Sivananthan (S)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).
ORCID: 0009-0008-2555-7282

Mark Walterfang (M)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).
ORCID: 0000-0002-1389-3691

Pierre Wibawa (P)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).
ORCID: 0000-0002-7120-6984

Michael Strupp (M)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).
ORCID: 0000-0002-9544-2279

Kyriakos Martakis (K)

From University Hospital Bern, Bern, Switzerland (T.B.-E., M.G.); Royal Free London NHS Foundation Trust (U.R., F.G.), University College London (U.R.), and Great Ormond Street Hospital, University College London (P.G., S.S.), London, Royal Manchester Children's Hospital, University of Manchester, Manchester (S.J.), and RK Statistics, Bakewell (R.K.) - all in the United Kingdom; Emma Children's Hospital-Amsterdam, University Medical Center, Amsterdam (M.B.); the National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovakia (T.F., M.K.); Justus Liebig University, Giessen (A.H., K.M.), SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim (L.A.-K., E.M.), University of Münster, Münster (T.M., J.H.P.), Ludwig Maximilian University, Munich (S.A.S., M.S.), and University of Cologne, Cologne (K.M.) - all in Germany; First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic (S.R.); and the Royal Melbourne Hospital, Melbourne, VIC, Australia (M.W., P.W.).
ORCID: 0000-0003-3982-0914

Classifications MeSH