Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial.

Child Humans Infant Muscular Atrophy, Spinal / genetics Spinal Muscular Atrophies of Childhood / genetics Survival of Motor Neuron 2 Protein / genetics

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
07 2022
Historique:
received: 18 02 2022
accepted: 10 05 2022
pubmed: 18 6 2022
medline: 27 7 2022
entrez: 17 6 2022
Statut: ppublish

Résumé

Most children with biallelic SMN1 deletions and three SMN2 copies develop spinal muscular atrophy (SMA) type 2. SPR1NT ( NCT03505099 ), a Phase III, multicenter, single-arm trial, investigated the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated within six postnatal weeks. Of 15 children with three SMN2 copies treated before symptom onset, all stood independently before 24 months (P < 0.0001; 14 within normal developmental window), and 14 walked independently (P < 0.0001; 11 within normal developmental window). All survived without permanent ventilation at 14 months; ten (67%) maintained body weight (≥3rd WHO percentile) without feeding support through 24 months; and none required nutritional or respiratory support. No serious adverse events were considered treatment-related by the investigator. Onasemnogene abeparvovec was effective and well-tolerated for presymptomatic infants at risk of SMA type 2, underscoring the urgency of early identification and intervention.

Identifiants

DOI: 10.1038/s41591-022-01867-3 PMID: 35715567 PMC: PMC9205287
pubmed: 35715567
doi: 10.1038/s41591-022-01867-3
pii: 10.1038/s41591-022-01867-3
pmc: PMC9205287
doi:

Substances chimiques

SMN2 protein, human 0
Survival of Motor Neuron 2 Protein 0
Zolgensma 0

Banques de données

ClinicalTrials.gov
['NCT03505099']

Types de publication

Clinical Trial, Phase III Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1390-1397

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

© 2022. The Author(s).

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Auteurs

Kevin A Strauss (KA)

Clinic for Special Children, Strasburg, PA, USA. kstrauss@clinicforspecialchildren.org.
Penn Medicine-Lancaster General Hospital, Lancaster, PA, USA. kstrauss@clinicforspecialchildren.org.
Departments of Pediatrics and Molecular, Cell & Cancer Biology, University of Massachusetts School of Medicine, Worcester, MA, USA. kstrauss@clinicforspecialchildren.org.
ORCID: 0000-0002-6429-8657

Michelle A Farrar (MA)

Department of Neurology, Sydney Children's Hospital Network, Sydney, NSW, Australia.
School of Clinical Medicine, UNSW Medicine and Health, UNSW Sydney, Sydney, NSW, Australia.
ORCID: 0000-0002-4472-0902

Francesco Muntoni (F)

The Dubowitz Neuromuscular Centre, University College London, Great Ormond Street Institute of Child Health & Great Ormond Street Hospital, London, UK.
National Institute of Health Research, Great Ormond Street Hospital Biomedical Research Centre, London, UK.

Kayoko Saito (K)

Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
ORCID: 0000-0003-2632-0873

Jerry R Mendell (JR)

Center for Gene Therapy, Nationwide Children's Hospital, Columbus, OH, USA.
Department of Pediatrics and Department of Neurology, The Ohio State University, Columbus, OH, USA.

Laurent Servais (L)

Department of Paediatrics, MDUK Oxford Neuromuscular Centre, Oxford, UK.
Neuromuscular Reference Center, Department of Pediatrics, CHU & University of Liège, Liège, Belgium.
ORCID: 0000-0001-9270-4061

Hugh J McMillan (HJ)

Department of Pediatrics, Neurology & Neurosurgery, Montreal Children's Hospital, McGill University, Montreal, QC, Canada.
ORCID: 0000-0001-8927-2018

Richard S Finkel (RS)

Department of Pediatrics, Nemours Children's Hospital, Orlando, FL, USA.
Center for Experimental Neurotherapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.
ORCID: 0000-0002-9351-7054

Kathryn J Swoboda (KJ)

Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
ORCID: 0000-0002-4593-6342

Jennifer M Kwon (JM)

Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

Craig M Zaidman (CM)

Washington University School of Medicine, St. Louis, MO, USA.

Claudia A Chiriboga (CA)

Division of Pediatric Neurology, Columbia University Medical Center, New York, NY, USA.

Susan T Iannaccone (ST)

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
ORCID: 0000-0003-0851-3516

Jena M Krueger (JM)

Department of Neurology, Helen DeVos Children's Hospital, Grand Rapids, MI, USA.

Julie A Parsons (JA)

Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.

Perry B Shieh (PB)

Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

Sarah Kavanagh (S)

Novartis Gene Therapies, Inc., Bannockburn, IL, USA.

Melissa Wigderson (M)

Novartis Gene Therapies, Inc., Bannockburn, IL, USA.

Sitra Tauscher-Wisniewski (S)

Novartis Gene Therapies, Inc., Bannockburn, IL, USA.

Bryan E McGill (BE)

Translational Medicine, Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
ORCID: 0000-0002-3552-7369

Thomas A Macek (TA)

Novartis Gene Therapies, Inc., Bannockburn, IL, USA.
ORCID: 0000-0001-7688-1818

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Classifications MeSH

Recherchemedicale.com › Personnes › Tranches d'âge › Enfant › Onasemnogene abeparvovec for presymptomatic...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Onasemnogene abeparvovec for presymptomatic...
Recherchemedicale.com › Personnes › Tranches d'âge › Nourrisson › Onasemnogene abeparvovec for presymptomatic...
Recherchemedicale.com › Maladies du système nerveux › Maladies neuromusculaires › Maladies du motoneurone › Amyotrophie spinale › Onasemnogene abeparvovec for presymptomatic...
Recherchemedicale.com › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Maladies neurodégénératives héréditaires › Amyotrophies spinales infantiles › Onasemnogene abeparvovec for presymptomatic...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines de liaison à l'ARN › Protéines du complexe SMN › Protéine-2 de survie du motoneurone › Onasemnogene abeparvovec for presymptomatic...