American clinicians report their experience of gene therapy treatment of two twins with proximal spinal muscular atrophy (SMA) who were born prematurely.
- The twins were born at 30 weeks and 2 days gestation due to a decelerated heart rate in one of the girls; they weighed 1560 and 1590 grams.
- Genetic analysis revealed no copy of SMN1 and a single copy of SMN2.
- The twins were treated while still asymptomatic with prednisolone 1 mg/kg followed by 1.1 x1014 vg per kg on day 24 of life (33 weeks and 5 days gestation).
- At the age of two, their motor function was normal.
- A moderate delay in speech and language acquisition was observed in both girls at 30 months.
- Post-hoc analyses revealed the presence of a positive modifier variant in the copy of SMN2 (the SMN2 gene in this case being an SMN2-SMN1 hybrid), which would correspond to an SMA phenotype with two copies of SMN2.
- The combination of the presence of this variant and presymptomatic treatment could explain the efficacy of gene therapy in these twins.
