Medication Summary

In December 2016, the FDA approved nusinersen, the first drug approved to treat children (including newborns) and adults with spinal muscular atrophy (SMA). The recombinant AAV9-based gene therapy, onasemnogene abeparvovec, was approved in May 2019 for SMA type 1 in children aged 2 years or younger. Risdiplam, a SMN2 splicing modifier, was approved in August 2020 for spinal muscular atrophy, including types 1, 2, and 3, in adults and children aged 2 months or older. Risdiplam gain FDA approval for children younger than 2 months in May 2022.

Class Summary

Antisense oligonucleotides (ASO) designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency may be considered for treatment.

Nusinersen (Spinraza)

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In studies in transgenic animal models of SMA, nusinersen was shown to increase exon 7 inclusion in SMN2 messenger ribonucleic acid (mRNA) transcripts and production of full-length SMN protein. It is indicated for SMA in pediatric and adults patients.

Class Summary

Recombinant gene therapy provides specificity to precisely treat gene deficiency.

Onasemnogene abeparvovec (Zolgensma)

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Recombinant AAV9-based gene therapy designed to deliver a copy of the gene encoding the human survival motor neuron (SMN) protein. It is indicated for gene replacement therapy in children aged 2 years or younger with spinal muscular atrophy (SMA) type 1 (also called Werdnig-Hoffman disease) who have biallelic mutation in the survival motor neuron 1 (SMN1) gene.

Class Summary

Survival of motor neuron 2 (SMN2) mRNA splicing modifiers are designed to treat mutations in chromosome 5q that lead to SMN protein deficiency.

Risdiplam (Evrysdi)

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Risdiplam is indicated for spinal muscular atrophy, including types 1, 2, and 3, in adults and children.

Follow-up

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Author

Jeffrey Rosenfeld, MD, PhD, FAAN Professor of Neurology, Associate Chairman, Department of Neurology, Director, Neuromuscular ALS/MND Program, Medical Director, The Center for Restorative Neurology, Loma Linda University Health Systems

Jeffrey Rosenfeld, MD, PhD, FAAN is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Neurological Association, Society for Neuroscience

Disclosure: Nothing to disclose.

Coauthor(s)

Carmel Armon, MD, MSc, MHS Chair, Department of Neurology, Assaf Harofeh Medical Center, Tel Aviv University Sackler Faculty of Medicine, Israel

Carmel Armon, MD, MSc, MHS is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American College of Physicians, American Epilepsy Society, American Medical Association, American Neurological Association, American Stroke Association, Massachusetts Medical Society, Sigma Xi, The Scientific Research Honor Society

Disclosure: Received research grant from: Neuronix Ltd, Yoqnea'm, Israel<br/>Received income in an amount equal to or greater than $250 from: JNS - Associate Editor. UpToDate - Author Royalties.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA Professor of Pediatrics, Neurology, Neurosurgery, and Psychiatry, Medical Director, Tulane Center for Autism and Related Disorders, Tulane University School of Medicine; Pediatric Neurologist and Epileptologist, Ochsner Hospital for Children; Professor of Neurology, Louisiana State University School of Medicine

Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, American Medical Association, American Neurological Association, Association of Military Surgeons of the US, Child Neurology Society, Southern Pediatric Neurology Society

Disclosure: Nothing to disclose.

Additional Contributors

Bryan Tsao, MD Associate Professor, Department of Neurology, Loma Linda University; Chair and Service Chief, Department of Neurology, Loma Linda University Medical Center

Bryan Tsao, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Robert J Baumann, MD Professor of Neurology and Pediatrics, Department of Neurology, University of Kentucky College of Medicine

Robert J Baumann, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society

Disclosure: Nothing to disclose.

Theresa L LaBarte, DO Resident Physician, Department of Neurology, Loma Linda University Medical Center

Theresa L LaBarte, DO is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Sections Spinal Muscular Atrophy
Overview
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Spinal Muscular Atrophy Medication

Medication Summary

Antisense Oligonucleotides