Effect of nusinersen after 3 years of treatment in 57 young children with SMA in terms of SMN2 copy number or type.

Nusinersen SMN2 Spinal muscular atrophy

Journal

Archives de pediatrie : organe officiel de la Societe francaise de pediatrie
ISSN: 1769-664X
Titre abrégé: Arch Pediatr
Pays: France
ID NLM: 9421356

Informations de publication

Date de publication:
21 Dec 2023
Historique:
received: 30 01 2023
revised: 20 10 2023
accepted: 21 10 2023
medline: 23 12 2023
pubmed: 23 12 2023
entrez: 22 12 2023
Statut: aheadofprint

Résumé

Spinal muscular atrophy (SMA) is a rare genetic neuromuscular disorder due to an autosomal recessive mutation in the survival motor neuron 1 gene (SMN1), causing degeneration of the anterior horn cells of the spinal cord and resulting in muscle atrophy. This study aimed to report on the 36-month follow-up of children with SMA treated with nusinersen before the age of 3 years. Changes in motor function, nutritional and ventilatory support, and orthopedic outcomes were evaluated at baseline and 36 months after intrathecal administration of nusinersen and correlated with SMA type and SMN2 copy number. We found that 93% of the patients gained new motor skills during the 3 years-standing without help for 12 of 37 and walking with help for 11 of 37 patients harboring three SMN2 copies. No patients with two copies of SMN2 can stand alone or walk. Patients bearing three copies of SMN2 are more likely to be spared from respiratory, nutritional, and orthopedic complications than patients with two SMN2 copies. Children with SMA treated with nusinersen continue to make motor acquisitions at 3 years after initiation of treatment. Children with two SMN2 copies had worse motor, respiratory, and orthopedic outcomes after 3 years of treatment than children with three copies.

Sections du résumé

BACKGROUND BACKGROUND
Spinal muscular atrophy (SMA) is a rare genetic neuromuscular disorder due to an autosomal recessive mutation in the survival motor neuron 1 gene (SMN1), causing degeneration of the anterior horn cells of the spinal cord and resulting in muscle atrophy. This study aimed to report on the 36-month follow-up of children with SMA treated with nusinersen before the age of 3 years. Changes in motor function, nutritional and ventilatory support, and orthopedic outcomes were evaluated at baseline and 36 months after intrathecal administration of nusinersen and correlated with SMA type and SMN2 copy number.
RESULTS RESULTS
We found that 93% of the patients gained new motor skills during the 3 years-standing without help for 12 of 37 and walking with help for 11 of 37 patients harboring three SMN2 copies. No patients with two copies of SMN2 can stand alone or walk. Patients bearing three copies of SMN2 are more likely to be spared from respiratory, nutritional, and orthopedic complications than patients with two SMN2 copies.
CONCLUSION CONCLUSIONS
Children with SMA treated with nusinersen continue to make motor acquisitions at 3 years after initiation of treatment. Children with two SMN2 copies had worse motor, respiratory, and orthopedic outcomes after 3 years of treatment than children with three copies.

Identifiants

pubmed: 38135619
pii: S0929-693X(23)00211-7
doi: 10.1016/j.arcped.2023.10.009
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023. Published by Elsevier Masson SAS.

Déclaration de conflit d'intérêts

Declaration of Competing Interest JD, CV, MGGB, and UWL received funding as scientific advisory boards member from Biogen. VL, FA, JD, AI, MCN, JBD, CET, MGGB, and UWL received funding as scientific advisory boards member from Novartis. JD, CC, MGGB, and ID received funding as scientific advisory boards member from Roche. ID received funding as scientific advisory boards member from PTC therapeutics. CC, CET, and UWL received funding as scientific advisory boards member from Pfizer. VL, FA, CB, AI, JBD, CS, and ID received compensations for presentation from Novartis. FA, CB, JBD, CV, and CET received compensations for presentation from Biogen. CC received compensations for presentation from Roche. CS received compensations for presentation from PTC therapeutics and Sanofi Adventis. CC and ID received compensations for presentation from Pfizer. JBD is investigator for ongoing Roche clinical trials. MGGB is sub-investigator in SMA studies for Biogen, Novartis, and Roche. SMD, MC, and MB, declare that they have no competing interests.

Auteurs

Frédérique Audic (F)

Centre de Référence des Maladies Neuromusculaires de l'enfant PACARARE, Service de Neuropédiatrie, Hôpital Timone Enfants, 264 rue Saint Pierre, 13385, Marseille Cedex 5, France. Electronic address: frederique.audic@ap-hm.fr.

Sonia M Dubois (SM)

Centre de Référence des Maladies Neuromusculaires de l'enfant PACARARE, Service de Neuropédiatrie, Hôpital Timone Enfants, 264 rue Saint Pierre, 13385, Marseille Cedex 5, France.

Julien Durigneux (J)

Centre de Référence des Maladies Neuromusculaires AOC, CHU d'Angers, Angers, France.

Christine Barnerias (C)

Centre de Référence des Maladies Neuromusculaires Nord/Ile de France/Est, Service de Neurologie pédiatrique, Hôpital Necker-Enfants Malades, APHP, Paris, France.

Arnaud Isapof (A)

Centre de Référence des Maladies Neuromusculaires Nord/Ile de France/Est, Service de Neuropédiatrie, Hôpital Trousseau, APHP, Paris, France.

Marie-Christine Nougues (MC)

Centre de Référence des Maladies Neuromusculaires Nord/Ile de France/Est, Service de Neuropédiatrie, Hôpital Trousseau, APHP, Paris, France.

Jean-Baptiste Davion (JB)

Centre de Référence des Maladies Neuromusculaires Nord/Ile de France/Est, Service de Neuropédiatrie, Hôpital Salengro CHU Lille, Lille, France.

Christian Richelme (C)

Centre de Référence des Maladies Neuromusculaires PACARARE, Hôpitaux Pédiatriques de Nice CHU - Lenval, Nice, France.

Carole Vuillerot (C)

Centre de Référence des Maladies Neuromusculaires de l'enfant PACARARE, Service de MPR pédiatrique L'Escale Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France.

Laure Legoff (L)

Centre de Référence des Maladies Neuromusculaires de l'enfant PACARARE, Service de MPR pédiatrique L'Escale Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France.

Pascal Sabouraud (P)

Centre de Référence des Maladies Neuromusculaires Nord/Ile de France/Est, Site Reims enfant AMH, CHU Reims, Reims, France.

Claude Cances (C)

Centre de Référence des Maladies Neuromusculaires AOC, Unité de Neurologie Pédiatrique, Hôpital des Enfants CHU Toulouse, Toulouse, France.

Vincent Laugel (V)

Centre de Référence des Maladies Neuromusculaires Nord/Ile de France/Est, Pédiatrie médico-chirurgicale, CHU de Strasbourg - Hôpital de Hautepierre, Strasbourg, France.

Juliette Ropars (J)

Centre de Référence des Maladies Neuromusculaires AOC, Service de Pédiatrie, CHRU de Brest, Brest, France.

Caroline Espil-Taris (C)

Centre de Référence des Maladies Neuromusculaires AOC, Unité de Neurologie pédiatrique, CHU Pellegrin, Bordeaux, France.

Valérie Trommsdorff (V)

Centre de Référence des Maladies Neuromusculaires PACARARE, Service de Pédiatrie, CHU La Réunion, Saint-Pierre, France.

Anne Pervillé (A)

Centre de Compétence des Maladies Neuromusculaires PACARARE, Service de Pédiatrie, CHU La Réunion, Saint-Denis, France.

Marta Gomez Garcia-de-la-Banda (MG)

Centre de Référence des Maladies Neuromusculaires Nord/Ile de France/Est, Hôpital Raymond Poincaré, APHP, Garches, France.

Hervé Testard (H)

Centre de Compétence des Maladies Neuromusculaires PACARARE, Neuropédiatrie, Clinique Universitaire Pédiatrique, Hôpital Couple Enfant - CHU Grenoble, Grenoble, France.

Mondher Chouchane (M)

Centre de Compétence des Maladies Neuromusculaires Nord/Ile de France/Est, Service de pédiatrie 1, Hôpital d'Enfants, CHU Dijon Bourgogne, Dijon, France.

Ulrike Walther-Louvier (U)

Centre de Référence des Maladies Neuromusculaires AOC, Service de Neuropédiatrie CHU Montpellier, Montpellier, France.

Cyril Schweizer (C)

Centre de Référence des Maladies Neuromusculaires Nord/Ile de France/Est, CHRU de Nancy, Hôpital d'Enfants, Vandoeuvre-Lès, Nancy, France.

Cécile Halbert (C)

Centre de Référence des Maladies Neuromusculaires de l'enfant PACARARE, Service de Neuropédiatrie, Hôpital Timone Enfants, 264 rue Saint Pierre, 13385, Marseille Cedex 5, France.

Myriam Badri (M)

Centre de Référence des Maladies Neuromusculaires de l'enfant PACARARE, Service de Neuropédiatrie, Hôpital Timone Enfants, 264 rue Saint Pierre, 13385, Marseille Cedex 5, France.

Susana Quijano-Roy (S)

Centre de Référence des Maladies Neuromusculaires Nord/Ile de France/Est, Hôpital Raymond Poincaré, APHP, Garches, France.

Brigitte Chabrol (B)

Centre de Référence des Maladies Neuromusculaires de l'enfant PACARARE, Service de Neuropédiatrie, Hôpital Timone Enfants, 264 rue Saint Pierre, 13385, Marseille Cedex 5, France.

Isabelle Desguerre (I)

Centre de Référence des Maladies Neuromusculaires Nord/Ile de France/Est, Service de Neurologie pédiatrique, Hôpital Necker-Enfants Malades, APHP, Paris, France.

Classifications MeSH