Background: Spinal muscular atrophy (SMA) is a rare, progressive motor neuron disease. Recent development of disease modifying therapies (DMT) has changed the natural history of SMA. Current FDA-approved DMTs include Onasemnogene abeparvovec (Zolgensma), Nusinersen (Spinraza), and Risdiplam (Evrysdi). Inclusion of SMA testing in newborn screening has allowed for rapid treatment. Despite rapid testing and treatment initiation, infants with severe phenotypes can continue to develop SMA-related symptoms. There is limited data on the use of combination DMT in SMA.
Objective: The goal of this study is to describe the outcomes of children who received Zolgensma gene therapy within the first 2 months of life. We additionally sought to determine the timing and reasons for supplemental DMT (Risdiplam or Nusinersen) in these patients.
Study Design: This is a case series of infants at Stanford University with genetically-confirmed SMA type 1 (0 copies SMN1, 2 copies SMN2) who were identified on newborn screen and received Zolgensma gene therapy within the first 2 months of life. Demographics, symptoms, milestones, exam, functional scoring, therapies, and biomarkers were noted.
Results: Eight children were included. Average age of gene therapy was 3.75 (range 1-8) weeks of life, and 3 patients were bridged with Risdiplam prior to gene therapy. All 8 patients were eventually started on an additional DMT (6 Risdiplam, 1 Spinraza, 1 Spinraza then switched to Risdiplam). Subsequent improvements were seen in all patients.
Conclusion: This case series illustrates real-world experiences managing infants with SMA type 1 (0 copies SMN1, 2 copies SMN2) after Zolgensma gene therapy. Despite the efficacy of gene therapy, progression of motor neuron symptoms can occur in infants with severe SMA phenotypes. Rapid initiation of supplemental DMT (Risdiplam or Nusinersen) may optimize outcomes of these patients. This data highlights the need for further guidelines on when to start additional agents.