Gene therapy in advanced metachromatic leukodystrophy: tempering expectations

Daphne H. Schoenmakers; Shanice Beerepoot; Laura A. Adang; Marije A.B.C. Asbreuk; Caroline G. Bergner; Annette E. Bley; Jaap-Jan Boelens; Valeria Calbi; Alejandra Darling; Erik Eklund; Ángeles García Cazorla; Sabine W. Grønborg; Samuel Groeschel; Peter M. van Hasselt; Carla E.M. Hollak; Claire Horgan; Simon Jones; Tom de Koning; Lucia Laugwitz; Caroline Lindemans; Pascal Martin; Fanny Mochel; Andreas Øberg; Dipak Ram; Caroline Sevin; Ludger Schöls; Ayelet Zerem; Nicole I. Wolf; Francesca Fumagalli

doi:10.1093/procel/pwae065

Protein Cell ›› 2025, Vol. 16 ›› Issue (1) : 12 -15. DOI: 10.1093/procel/pwae065

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Gene therapy in advanced metachromatic leukodystrophy: tempering expectations

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¹. Department of Child Neurology, Amsterdam Leukodystrophy Center, Amsterdam UMC Location Vrije Universiteit Amsterdam, Emma’s Children’s Hospital, Boelelaan 1117, Amsterdam, The Netherlands

². Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Cellular and Molecular Mechanisms, Amsterdam Neuroscience, De Boelelaan 1117, Amsterdam, The Netherlands

³. Medicine for Society, Platform at Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands

⁴. Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, United States

⁵. Leukodystrophy Center, Clinic for Neurology, University hospital Leipzig, 04103 Leipzig, Germany

⁶. University Children’s Hospital, University Medical Center Hamburg Eppendorf, 20251 Hamburg, Germany

⁷. Department of Pediatrics, Stem Cell Transplantation and Cellular Therapies Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States

⁸. San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), Pediatric Immunohematology Unit, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, Milan 20132, Italy

⁹. Metabolic Unit, Neurology Department, Sant Joan de Déu Children’s Hospital, Barcelona, Spain

¹⁰. Section for Pediatric Neurology, Skåne University Hospital and Clinical Sciences, Lund University, Lund 221 84, Sweden

¹¹. Department of Pediatrics and Adolescent Medicine and Department of Clinical Genetics, Center for Inherited Metabolic Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

¹². Department of Paediatric Neurology and Developmental Medicine, University Children’s Hospital, Tübingen, Germany

¹³. Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands

¹⁴. Department of Endocrinology and Metabolism, Amsterdam UMC Location AMC, Amsterdam UMC, Meibergdreef 9, University of Amsterdam, Amsterdam, The Netherlands

¹⁵. Department of Paediatric Bone Marrow Transplant and Cellular Therapy, Royal Manchester Children’s Hospital, Manchester University NHS Foundation Trust, United Kingdom

¹⁶. Genomic Medicine, St Mary’s Hospital, Manchester University NHS Foundation Trust, United Kingdom

¹⁷. Neuropediatrics, General Pediatrics, Diabetology, Endocrinology and Social Pediatrics, University of Tuebingen, University Hospital Tübingen, Tübingen 72016, Germany

¹⁸. Institute for Medical Genetics and Applied Genomics, University of Tübingen, Tübingen 72070, Germany

¹⁹. Department of Pediatric Hematopoietic Stem Cell Transplantation, UMC Utrecht and Princess Maxima Center, The Netherlands

²⁰. Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen 72070, Germany

²¹. Sorbonne Université, Institut du Cerveau, Inserm, CNRS, AP-HP, Paris, France

²². Department of Genetics, AP-HP, Hôpital Pitié-Salpêtrière, DMU BioGeM, Paris, France

²³. Norwegian National Unit for Newborn Screening, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Norway

²⁴. Department of Paediatric Neurology, Royal Manchester Children’s Hospital, United Kingdom

²⁵. Pediatric Neurology Department, Reference Center for Leukodystrophies, Hôpital Bicêtre, Le Kremlin Bicêtre, France

²⁶. Department of Neurology and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen 72070, Germany

²⁷. German Center of Neurodegenerative Diseases (DZNE), Tübingen, Germany

²⁸. Faculty of Medicine and Health Sciences, Tel Aviv Sourasky Medical Center, Pediatric Neurology Institute, Dana-Dwek Children’s Hospital, Tel Aviv University, Tel Aviv, Israel

²⁹. Pediatric Immunohematology Unit and Neurology and Neurophysiology Unit, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, Milan 20132, Italy

d.h.schoenmakers@amsterdamumc.nl

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Daphne H. Schoenmakers, Shanice Beerepoot, Laura A. Adang, Marije A.B.C. Asbreuk, Caroline G. Bergner, Annette E. Bley, Jaap-Jan Boelens, Valeria Calbi, Alejandra Darling, Erik Eklund, Ángeles García Cazorla, Sabine W. Grønborg, Samuel Groeschel, Peter M. van Hasselt, Carla E.M. Hollak, Claire Horgan, Simon Jones, Tom de Koning, Lucia Laugwitz, Caroline Lindemans, Pascal Martin, Fanny Mochel, Andreas Øberg, Dipak Ram, Caroline Sevin, Ludger Schöls, Ayelet Zerem, Nicole I. Wolf, Francesca Fumagalli. Gene therapy in advanced metachromatic leukodystrophy: tempering expectations. Protein Cell, 2025, 16(1): 12-15 DOI:10.1093/procel/pwae065

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References

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