Safety and efficacy of gene therapy for patients with spinal muscular atrophy: a real-life study in a Brazilian cohort

Background: Spinal muscular atrophy (SMA) is a genetic motor neuron disease caused by mutations in the SMN1 (Survival Motor Neuron) gene, which leads to hypotonia and muscle weakness with high mortality related to respiratory involvement. Gene therapy (GT) (onasemnogeno aberpavovec) for SMA, through an adeno-associated viral vector 9 (AAV9) was recently approved in our country, but its safety and efficacy outside the context of clinical trials is still poorly understood.

Objective: To present early results regarding safety and efficacy in SMA patients treated with GT.

Methods: We followed a total of 33 patients treated with GT for SMA from 6 months to 1 year of treatment. The patients were evaluated by the functional scales CHOP-INTEND (The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders) and in relation to gain of motor milestones. In addition, assessment of survival and use of continuous ventilation (CV) was performed and also data regarding transaminase elevation, liver function, hematological data, elevation of troponin and duration of corticosteroid use.

Results: 33 patients were included, 26 SMA type 1 and 7 SMA type 2. The mean age at dosing was 18.5 months (14.0 - 23.2), with a mean weight of 9.9 kg (8.3 kg). – 16.3) and 28 patients (87.5%) were using nusinersen previously. After 1 year of treatment 32 patients (96.9%) were alive, 7 patients (21.2%) remained on CV (>16h/day) versus 11 (33.3%) patients at dosing. Regarding the gain in the CHOP-INTEND score, the mean baseline score was 30.50 (19.50, 40.75) to 46 (40.00, 52.00) at 6 months and to 56 (50.00, 58.00) points at 12 months. Regarding motor milestones, from those with SMA type 1, nine patients (42.9%) sat and four patients (19%) stood with support, and three patients acquired gait with support among SMA type 2. In terms of safety, the highest transaminase peak occurred in weeks 3 and 6 after infusion. Only 10 patients (30.3%) had transaminase levels similar to baseline at week 8. 15 patients (45.4%) had thrombocytopenia in the first week and one patient met criteria for thrombotic microangiopathy. The mean time of prednisolone use was 105 days (60.0 – 122.2).

Conclusions: GT is effective in real life but with the potential for serious adverse events. There is a need for strict monitoring of transaminases, platelets and troponin and the occurrence of liver damage beyond 2 months of drug use, especially in patients with an older profile than in clinical studies.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
18 September 2023