0784 Spinal Muscular Atrophy 1 Genetic Therapies Halt Development of Infantile Onset Sleep-Related Disordered Breathing

Abstract Introduction Natural history studies of Spinal Muscular Atrophy Type 1 demonstrate that patients typically require non-invasive ventilatory interventions in the first year of life for sleep-related disordered breathing (e.g. obstructive sleep apnea, central sleep apnea, and hypoventilation) due to the progressive development of neuromuscular weakness. There are currently no reports that analyze the effects that disease-modifying therapy has on the development of sleep-related disordered breathing. Methods This descriptive retrospective cohort study will utilize a Kaplan-Meier time-to-event analysis to determine whether administration of disease-modifying therapy delays diagnosis of sleep-related disordered breathing and halts initiation of ventilatory assistance in the first year of life. Results Six patients with spinal muscular atrophy type 1 followed by the division of pediatric neurology were included in the cohort. One patient received both nusinersen and onasemnogene abeparvovec in the first year of life and two patients received onasemnogene abeparvovec in the first year of life followed by risdiplam after one year of life. Three patients exclusively received onasemnogene abeparvovec in the first year of life. Four of the patients did not receive a sleep study, as respiratory pathology was not a concern at follow up visits due to preservation or improvement of motor strength. The two that received polysomnograms were diagnosed with obstructive sleep apnea after the first year of life with an average AHI of 4.1, average SpO2 nadir of 81.5%, and average total arousal index of 10. Conclusion Though a small sample size, there is some evidence to suggest that prompt initiation of disease-modifying therapy such as nusinersen, onasemnogene abeparvovec, ,and risdiplam can possibly halt the development of sleep-related disordered breathing in the first year of life and delay initiation of ventilatory support. Further controlled trials would be needed to further understand the relationship between disease-modifying therapy and sleep-related respiratory outcomes in pediatric patients with SMA type 1. Support (if any)