2023 American Academy of Neurology Abstract Website

Objective:

To describe twin girls with spinal muscular atrophy (SMA) with1 copy of SMN2 who received Onsasemnogene-abeparvove at 33 weeks’ gestation.

Background:

SMA is a neurodegenerative disorder caused by absence of SMN1 resulting in loss of motor neurons and thus progressive muscle weakness and atrophy. SMN2 copy number modifies phenotype. Patients with 1 SMN2 copy have a severe form of the disease resulting in limited survival after birth. Pre-clinical and clinical data has shown that early treatment of SMA is critical for optimal outcomes. Onsasemnogene-abeparvove, an adeno-associated virus vector mediated gene therapy, is approved for treatment of SMA in children less than 2 years of age, but few cases have reported its impact in premature infants.

Design/Methods:

Exempt from consent by IRB review.

Results:

Twin monochorionic, monoamniotic girls were born at 30 weeks and 2 days gestation. SMA was suggested on newborn screen and confirmatory testing showed 0 copies of SMN1 and 1 copy of SMN2. They received Onsasemnogene-abeparvove at 33 weeks’ gestation. Neither child had adverse events associated with the medication. Both girls sat without support and rolled over at 8 months (6 months corrected age), crawled, pulled to stand, and said one-word phrases at 12 months, and walked independently at 15 months of age. Neurological exam at 19 months of age showed normal muscle bulk, tone and strength and normal reflexes.

Conclusions:

This case report is important because it demonstrates the potential for excellent outcomes, even in children predicted to have extremely severe disease. Normally, SMN protein level falls during the last trimester and first few months after birth (Ramos, et al, 2019). These twins were treated at the beginning of the last trimester of pregnancy, very early in this proposed critical window for treatment, likely contributing to normal development.