Gene Therapy for Spinal Muscular Atrophy is Considerably Effective When Administered as Early as Possible after Birth

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 suggest 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.

Note:

Funding Declaration: This work was supported in part by a Health and Labor Sciences Research Grant for Research on Rare and Intractable Diseases from the Ministry of Health, Labour and Welfare, Japan [grant number JPMH20FC1025]; a Grant-in-Aid for the Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development [AMED; grant numbers JP19ek0109276, JP20ek0109482]; and a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan [Japan Society for the Promotion of Science [JSPS] KAKENHI; grant number JP20K08207, JP20K08259].

Conflict of Interest: akaaki Sawada, Kimitoshi Nakamura, Kotaro Yuge, and Shiro Ozasa have receivedhave received speaker honoraria from Chugai Pharmaceutical for activities unrelated to the present work. The remaining authors declare no competing interests. speaker honoraria from Biogen Japan and Novartis Japan. Kotaro Yuge and Shiro Ozasa

Ethical Information: We have obtained informed consent from the parents of the patients to publish these cases, as the report includes the patients' detailed medical histories that may lead to their identification.

Keywords: Gene therapy, newborn screening, onasemnogene abeparvovec, spinal muscular atrophy, SMN1