Gene therapy for spinal muscular atrophy is considerably effective when administered as early as possible after birth

Takaaki Sawada; Jun Kido; Yukako Yae; Kotaro Yuge; Keiko Nomura; Kentaro Okada; Natsumi Fujiyama; Shiro Ozasa; Kimitoshi Nakamura

doi:10.1016/j.ymgmr.2023.100973

Gene therapy for spinal muscular atrophy is considerably effective when administered as early as possible after birth

Mol Genet Metab Rep. 2023 Apr 5:35:100973. doi: 10.1016/j.ymgmr.2023.100973. eCollection 2023 Jun.

Authors

Takaaki Sawada^{1

2

3}, Jun Kido^{2

3}, Yukako Yae⁴, Kotaro Yuge⁴, Keiko Nomura³, Kentaro Okada³, Natsumi Fujiyama³, Shiro Ozasa³, Kimitoshi Nakamura²

Affiliations

¹ Southern Kyushu and Okinawa Unit Center of The Japan Environment and Children's Study, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
² Department of Pediatrics, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
³ Department of Pediatrics, Kumamoto University Hospital, Kumamoto, Japan.
⁴ Department of Pediatrics and Child Health, Kurume University School of Medicine, Fukuoka, Japan.

Abstract

Introduction: Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by muscle atrophy and progressive muscle weakness. Insurance-approved treatments in Japan include antisense oligonucleotide therapy, gene therapy, and small molecule therapy. The efficacy of these therapies varies depending on the timing of treatment initiation.

Case presentation: We report the cases of two infants with SMA born in the same region. Patient 1, who had two copies of SMN2, was born before newborn screening (NBS) was started and received onasemnogene abeparvovec therapy at the age of 4 months. Patient 2, who had three copies of SMN2, was born after the start of NBS and was diagnosed and treated with onasemnogene abeparvovec before symptoms appeared. Unfortunately, Patient 1 became bedridden despite receiving gene therapy, while Patient 2 achieved normal motor development.

Discussion: Our findings show that treatment timing is an essential factor affecting patients' motor neurodevelopmental outcomes, although our patients did have differences in the number of copies of SMN2. Therefore, a system should be established to allow all newborns to undergo publicly funded NBS for SMA.

Keywords: Gene therapy; Newborn screening; Onasemnogene abeparvovec; SMN1; Spinal muscular atrophy.

Publication types

Case Reports