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Medicines update
Gene therapy for spinal muscular atrophy
  1. Vasantha Lakshmi Gowda1,
  2. Heinz Jungbluth1,2,
  3. Elizabeth Wraige1
  1. 1 Department of Paediatric Neurology, Evelina London Children's Hospital, London, UK
  2. 2 Randall Division for Cell and Molecular Biophysics, Muscle Signalling Section, King's College, London, UK
  1. Correspondence to Dr Vasantha Lakshmi Gowda, Paediatric Neurosciences, Evelina London Children's Hospital, London, SE1 7EH, UK; vasantha.gowda{at}gstt.nhs.uk

https://doi.org/10.1136/archdischild-2023-325359

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    Glossary

    • Vg/kg = vector genomes/kilogram

    • SMA = Spinal Muscular Atrophy

    • AAV9 = Adeno-associated virus serotype 9

    • CHOP-INTEND: Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders, a motor assessment tool devised for infants with SMA. This has 16 items graded on a scale of 0 to 4, with 0 being no response and 4 being complete response.

    Introduction

    Spinal muscular atrophy (SMA) is a severe neurodegenerative condition resulting from recessive mutations in the SMN1 gene and insufficient survival motor neuron (SMN) protein production.1 Lack of SMN protein causes irreversible degeneration of lower motor neurons and consequential muscle atrophy and weakness. Onasemnogene abeparvovec, marketed under the name Zolgensma, directly replaces the SMN1 gene using a non-replicating, non-pathogenic modified adeno-associated virus serotype-9 (AAV9). In this article, we outline the patient selection process for treatment with onasemnogene abeparvovec, with some illustrative clinical examples.

    Indications

    In the USA, onasemnogene abeparvovec has been approved for the treatment of children with SMA, (including SMA type 2) up to the age of 2 years; in Europe including the UK, it has been approved for treatment of patients with 5q SMA with a biallelic mutation in the SMN1 gene and a clinical diagnosis of SMA type 1, or patients with 5q SMA with a biallelic mutation in the SMN1 gene and up to three copies of the SMN2 gene and presymptomatic infants with up to three SMN2 copies. In Australia, the drug is indicated for the treatment of children less than 9 months of age with symptomatic or presymptomatic SMA with biallelic mutations in the SMN1 gene and one to three copies of the SMN2 gene. In Japan, this is approved for the treatment of SMA in patients under the age of 2 years, including those who are presymptomatic at diagnosis.

    Mechanism of action/pharmacology

    Onasemnogene abeparvovec is infused intravenously over 1 hour. The dose …

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    Footnotes

    • Twitter @vasanthagowda

    • Contributors First and senior author VLG drafted the manuscript. HJ and EW have revised it critically.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests VLG has received consultancy/speaker honoraria from Novartis, Roche, Biogen, PTC Therapeutics, Pfizer and Sarepta Therapeutics. EW has received consultancy/speaker honoraria from Pfizer, Biogen and Novartis. HJ has received consultancy/honoraria from Pfizer.

    • Provenance and peer review Commissioned; externally peer reviewed.