Faculty Collaboration Database

Gene Therapy for Spinal Muscular Atrophy: Safety and Early Outcomes. Pediatrics 2020 Sep;146(3)

Date

08/28/2020

Pubmed ID

32843442

DOI

10.1542/peds.2020-0729

Scopus ID

2-s2.0-85090251066 (requires institutional sign-in at Scopus site)   78 Citations

Abstract

BACKGROUND AND OBJECTIVES: Historically, autosomal recessive 5q-linked spinal muscular atrophy (SMA) has been the leading inherited cause of infant death. SMA is caused by the absence of the SMN1 gene, and SMN1 gene replacement therapy, onasemnogene abeparvovec-xioi, was Food and Drug Administration approved in May 2019. Approval included all children with SMA age <2 years without end-stage weakness. However, gene transfer with onasemnogene abeparvovec-xioi has been only studied in children age ≤8 months.

METHODS: In this article, we report key safety and early outcome data from the first 21 children (age 1-23 months) treated in the state of Ohio.

RESULTS: In children ≤6 months, gene transfer was well tolerated. In this young group, serum transaminase (aspartate aminotransferase and alanine aminotransferase) elevations were modest and not associated with γ glutamyl transpeptidase elevations. Initial prednisolone administration matched that given in the clinical trials. In older children, elevations in aspartate aminotransferase, alanine aminotransferase and γ glutamyl transpeptidase were more common and required a higher dose of prednisolone, but all were without clinical symptoms. Nineteen of 21 (90%) children experienced an asymptomatic drop in platelets in the first week after treatment that recovered without intervention. Of the 19 children with repeated outcome assessments, 11% (n = 2) experienced stabilization and 89% (n = 17) experienced improvement in motor function.

CONCLUSIONS: In this population, with thorough screening and careful post-gene transfer management, replacement therapy with onasemnogene abeparvovec-xioi is safe and shows promise for early efficacy.

Author List

Waldrop MA, Karingada C, Storey MA, Powers B, Iammarino MA, Miller NF, Alfano LN, Noritz G, Rossman I, Ginsberg M, Mosher KA, Broomall E, Goldstein J, Bass N, Lowes LP, Tsao CY, Mendell JR, Connolly AM

Author

Nancy Bass MD Professor in the Neurology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenoviruses, Human
Age Factors
Alanine Transaminase
Aspartate Aminotransferases
Biological Products
Genetic Therapy
Genetic Vectors
Glucocorticoids
Humans
Infant
Ohio
Prednisolone
Recombinant Fusion Proteins
Spinal Muscular Atrophies of Childhood
Survival of Motor Neuron 1 Protein
gamma-Glutamyltransferase