The first prenatal treatment for spinal muscular atrophy showed promise in a single case report.1 SMA is a neurodegenerative disorder caused by reduced levels of survival motor neuron (SMN) protein due to deletions or mutations of the SMN1 gene.2 Researchers from St. Jude Children’s Research Hospital in Memphis, Tennessee, administered the disease-modifying therapy risdiplam in utero with the aim of preventing motor neuron degeneration before birth after the child tested positive for two copies of SMN2, which is predictive of the most severe form of SMA, type 1.
Risdiplam is an SMN2 pre-mRNA splicing modifier designed to increase and sustain SMN protein levels centrally and peripherally.3 It’s one of three drugs approved for SMA, the others being nusinersen and onasemnogene abeparvovec.
In this single-patient case, researchers administered risdiplam orally to the mother at a dose of 5 mg/day during the last six weeks of pregnancy. The mother underwent weekly monitoring for any drug-related side effects, while the fetus was assessed for growth, activity, and anatomical development through ultrasonography. This approach aimed to ensure both maternal safety and fetal well-being while attempting to mitigate the effects of SMA before birth.
Postnatal assessments of the infant have shown no clinical features of SMA, including hypotonia, weakness, areflexia, or fasciculations. The child’s motor function, muscle ultrasonographic imaging, and electrophysiological studies have been conducted every six months and have consistently demonstrated normal peripheral nerve and muscle development for the child’s age. These promising findings indicate that early intervention at the prenatal stage could be a viable strategy for preventing SMA symptoms from manifesting.
This case study highlights the potential benefits of prenatal therapy for SMA, reinforcing the importance of early genetic screening and intervention. Further studies are needed to validate these results in a larger cohort, to understand if in utero treatment could become a standard approach for managing SMA in high-risk pregnancies. The success of this intervention may also open the door to exploring similar prenatal treatments for other genetic neuromuscular diseases.
References:
1. Finkel RS, Hughes SH, Parker J, et al. Risdiplam for Prenatal Therapy of Spinal Muscular Atrophy. NEJM. 2025. DOI: 10.1056/NEJMc2300802
2. Ogbonmide T, Rathore R, Rangrej SB, et al. Gene Therapy for Spinal Muscular Atrophy (SMA): A Review of Current Challenges and Safety Considerations for Onasemnogene Abeparvovec (Zolgensma).Cureus. 2023;15:e36197.
3. Paik J. Risdiplam: A Review in Spinal Muscular Atrophy. CNS Drugs. 2022;36:401–410.
Disclosures: This article was created by the touchNEUROLOGY team utilizing AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.
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