Pediatric neurology
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Pediatric neurology · Nov 2019
ReviewFrom Clinical Trials to Clinical Practice: Practical Considerations for Gene Replacement Therapy in SMA Type 1.
Spinal muscular atrophy is a devastating neurodegenerative autosomal recessive disease that results from survival of motor neuron 1 (SMN1) gene mutation or deletion. Patients with spinal muscular atrophy type 1 utilizing supportive care, which focuses on symptom management, never sit unassisted, and 75% die or require permanent ventilation by age 13.6 months. Onasemnogene abeparvovec (Zolgensma, formerly AVXS-101) is a gene replacement therapy comprising an adeno-associated viral vector containing the human SMN gene under control of the chicken beta-actin promoter. ⋯ The only treatment-related adverse event observed was transient asymptomatic transaminasemia that resolved with a short course of prednisolone treatment. This review discusses the biological rationale underlying gene replacement therapy for spinal muscular atrophy, describes the onasemnogene abeparvovec clinical trial experience, and provides expert recommendations as a reference for the real-world use of onasemnogene abeparvovec in clinical practice. As of May 24, 2019, the Food and Drug Administration approved onasemnogene abeparvovec, the first gene therapy approved to treat children younger than two years with spinal muscular atrophy.