Real-world multidisciplinary outcomes of onasemnogene abeparvovec monotherapy in patients with spinal muscular atrophy type 1: experience of the French cohort in the first three years of treatment.

Autor: Desguerre I; IHU Imagine, Paris University, 24, Boulevard du Montparnasse, 75015, Paris, France.; Department of Pediatric Neurology, French Reference Center for Neuromuscular Diseases, AP-HP, Hôpital Necker-Enfants Malades, 149 rue de sèvres, 75015, Paris, France., Barrois R; Department of Pediatric Neurology, French Reference Center for Neuromuscular Diseases, AP-HP, Hôpital Necker-Enfants Malades, 149 rue de sèvres, 75015, Paris, France. remi.barrois@aphp.fr., Audic F; Department of Pediatric Neurology, French Reference Center for Neuromuscular Diseases, Hôpital Timone Enfants, 264 rue Saint-Pierre, 13385, Marseille, France., Barnerias C; Department of Pediatric Neurology, French Reference Center for Neuromuscular Diseases, AP-HP, Hôpital Necker-Enfants Malades, 149 rue de sèvres, 75015, Paris, France., Chabrol B; Department of Pediatric Neurology, French Reference Center for Neuromuscular Diseases, Hôpital Timone Enfants, 264 rue Saint-Pierre, 13385, Marseille, France., Davion JB; Department of Pediatric Neurology, French Reference Center for Neuromuscular Diseases, Lille University Hospital Center, 2 avenue Oscar Lambret, 59000, Lille, France., Durigneux J; Department of Pediatric Neurology, French Reference Center for Neuromuscular Diseases, Angers University Hospital Center, 4 rue Larrey, 49933, Angers, France., Espil-Taris C; Department of Pediatric Neurology, French Reference Center for Neuromuscular Diseases, Pellegrin University Hospital Center, Hôpital des Enfants, place Amélie-Raba-Léon, 33086, Bordeaux, France., Gomez-Garcia de la Banda M; Pediatric Neurology and ICU Department, Garches Reference Center for Neuromuscular Diseases (NEIF for FILNEMUS; RPC for Euro-NMD ERN), AP-HP Paris-Saclay Université, Hôpital Raymond Poincaré (UVSQ), 104 boulevard Raymond Poincaré, 92380, Garches, France., Guichard M; Department of Pediatric Neurology and Handicaps, French Competence Center for Neuromuscular Diseases, Boulevard Tonnellé, Hôpital Clocheville, 2 Boulevard Tonnellé, 37000, Tours, France., Isapof A; Department of Pediatric Neurology, AP-HP, French Reference Center for Neuromuscular Diseases, Hôpital Armand Trousseau, 26 avenue du Docteur Arnold-Netter, 75012, Paris, France., Nougues MC; Department of Pediatric Neurology, AP-HP, French Reference Center for Neuromuscular Diseases, Hôpital Armand Trousseau, 26 avenue du Docteur Arnold-Netter, 75012, Paris, France., Laugel V; Department of Pediatric Neurology, French Reference Center for Neuromuscular Diseases, Strasbourg University Hospital Center, Hôpital de Hautepierre, 1 avenue Molière, 67098, Strasbourg, France., Le Goff L; Department of Neuromuscular Pathology, French Reference Center for Neuromuscular Diseases, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, -Bron, 59 boulevard Pinel, 69677, Lyon-Bron, France., Mercier S; Department of Medical Genetics, French Reference Center for Neuromuscular Diseases, Nantes University Hospital Center, 1 Place Alexis-Ricordeau, 44093, Nantes, France., Pervillé A; Department of Pediatrics, French Competence Center for Neuromuscular Diseases, Hôpital d'Enfants ASFA, CS 81010, 97404, Saint Denis Cedex, Réunion, France., Richelme C; Department of Pediatric Neurology, French Reference Center for Neuromuscular Diseases, Nice University Hospital Center, Hôpital Lenval, 57 Avenue de la Californie, 06200, Nice, France., Thibaud M; Department of Pediatrics, French Reference Center for Neuromuscular Diseases, American Memorial Hospital, Reims University Hospital Center, 49 Rue Cognacq Jay, 51092, Reims, France., Sarret C; CMR Neuromusculaire, French Reference Center for Neuromuscular Diseases, Clermont-Ferrand University Hospital Center, Clermont-Ferrand, France., Schweitzer C; Department of Infant Medicine, French Reference Center for Neuromuscular Diseases, Nancy University Hospital Center, Rue du Morvan, 54511, Vandoeuvre lès Nancy, France., Testard H; Department of Pediatric Neurology, French Competence Center for Neuromuscular Diseases, Grenoble University Hospital Center, Hôpital Couple Enfant, Quai Yermolof, 38700, Grenoble, France., Trommsdorff V; Department of Pediatrics, French Reference Center for Neuromuscular Diseases, University Hospital Center, Avenue François Mitterrand, BP 350, 97448, Saint Pierre Cedex, Réunion, France., Vanhulle C; Department of Pediatrics, French Competence Center for Neuromuscular Diseases, Rouen University Hospital Center, Charles Nicolle, 1 Rue de Germont, 76031, Rouen, France., Walther-Louvier U; Department of Pediatric Neurology, French Greater South‒West Reference Center for Neuromuscular Diseases, Hôpital Gui de Chauliac, University Hospital Center Montpellier, 80 Avenue Augustin Fliche, 34295, Montpellier, France., Altuzarra C; Department of Pediatrics, French Reference Center for Neuromuscular Diseases, Besançon University Hospital Center - Hôpital Jean Minjoz, 3 boulevard A. Fleming, 25030, Besançon, France., Chouchane M; Department of Pediatric Neurology, French Competence Center for Neuromuscular Diseases, Dijon University Hospital Center, Hôpital d'Enfants, 14 rue Paul Gaffarel, 21079, Dijon, France., Ropars J; LaTIM INSERM UMR 1101, French Reference Center for Neuromuscular Diseases Brest University Hospital Center, Hôpital Morvan, Boulevard Tanguy Prigent, 29609, Brest, France., Quijano-Roy S; Pediatric Neurology and ICU Department, Garches Reference Center for Neuromuscular Diseases (NEIF for FILNEMUS; RPC for Euro-NMD ERN), AP-HP Paris-Saclay Université, Hôpital Raymond Poincaré (UVSQ), 104 boulevard Raymond Poincaré, 92380, Garches, France., Cances C; Department of Pediatric Neurology, French Greater South‒West Reference Center for Neuromuscular Diseases, Hôpital des Enfants, University Hospital Center Toulouse, 330 av de Grande Bretagne-TSA, 31059, Toulouse, France.
Jazyk: angličtina
Zdroj: Orphanet journal of rare diseases [Orphanet J Rare Dis] 2024 Sep 13; Vol. 19 (1), pp. 344. Date of Electronic Publication: 2024 Sep 13.
DOI: 10.1186/s13023-024-03326-3
Abstrakt: Background: Spinal muscular atrophy type 1 (SMA1) is the most severe and early form of SMA, a genetic disease with motor neuron degeneration. Onasemnogene abeparvovec gene transfer therapy (GT) has changed the natural history of SMA1, but real-world data are scarce.
Methods: A French national expert committee identified 95 newly diagnosed treatment-naive SMA1 patients between June 2019 and June 2022. We prospectively report on children treated with GT as the first and only therapy who had more than one-year of follow-up.
Results: Forty-six SMA1 patients received GT. Twelve patients received other treatments. Patients with respiratory insufficiency were oriented toward palliative care after discussion with families. Twenty-nine of the treated patients with more than 12 months of follow-up were included in the follow-up analysis. Among them, 17 had 24 months of follow-up. The mean age at treatment was 7.5 (2.1-12.5) months. Twenty-two patients had two SMN2 copies, and seven had three copies. One infant died in the month following GT due to severe thrombotic microangiopathy, and another died due to respiratory distress. Among the 17 patients with 24 months of follow-up, 90% required spinal bracing (15/17), three patients required nocturnal noninvasive ventilation, and two needed gastrostomy. Concerning motor milestones at the 24-month follow-up, all patients held their head, 15/17 sat for 30 s unassisted, and 12/17 stood with aid. Motor scores (CHOPINTEND and HINE-2) and thoracic circumference significantly improved in all patients.
Conclusions: Our study shows favorable motor outcomes and preserved respiratory and feeding functions in treatment-naive SMA1 infants treated by GT as the first and only therapy before respiratory and bulbar dysfunctions occurred. Nevertheless, almost all patients developed spinal deformities.
(© 2024. The Author(s).)
Databáze: MEDLINE
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