Describe the safe, tolerable administration of nusinersen in a prenatally diagnosed, postnatally confirmed, pre-symptomatic premature neonate with spinal muscular atrophy (SMA) type 1

SMA is a group of genetic motor neuron diseases secondary to loss of function mutations in the survival motor neuron (SMN1) gene characterized by anterior horn cell degeneration causing variable degrees of muscle weakness and atrophy. Nusinersen and onasemnogene abeparvovec-xioi are novel treatments for SMA that alter splicing to create a functional protein replacing the missing SMN1 or deliver an episome containing wild type SMN1 creating functional SMN1, respectively. Clinical trials have shown that initiation of either treatment demonstrates optimal effect when delivered at pre-symptomatic ages. However, onasemnogene abeparvovec-xioi requires steroid use.

Single patient case report with review of clinical presentation, management, course of hospitalization and follow up.

Neurology was consulted on a prenatally diagnosed male with SMA type 1 (0 SMN1 copies, 2 SMN2 copies) born at 30 weeks gestational age due to maternal HELLP syndrome. At birth, APGARS were 8 and 9. Serial neurological exams were normal for age without hypotonia. At 19 days old, after postnatal genetic confirmation of SMA, treatment with nusinersen began. He received four loading doses of nusinersen at 5 mL (12 mg) per protocol delivered over 72 days. At 147 days of life, after hospital discharge, he was given onasemnogene abeparvovex-xioi. He began receiving physical and occupational therapy at 9 days old and walked independently at 17 months of age. At his most recent neurology clinic visit (18 months) he was ambulating independently without falls. His CHOP-INTEND score was 36/64 at 7 weeks of life, 62/64 at 6 months of life, and 64/64 at 18 months of life.

This case demonstrates feasibility in the use of nusinersen in premature infants, as a bridge to the appropriate use of onasemnogene abeparvovex-xioi.