Onasemnogene abeparvovec (Zolgensma®) is a gene therapy approved for the treatment of spinal muscular atrophy (SMA). Administered as a one-time intravenous infusion, onasemnogene abeparvovec uses the adeno-associated virus vector to deliver a functional copy of the human survival motor neuron (SMN) gene to motor neuron cells. SMN1 encodes survival motor neuron protein, which is responsible for the maintenance and function of motor neurons. In clinical trials, onasemnogene abeparvovec improved event-free survival, motor function and motor milestone outcomes in patients with SMA, with these improvements maintained over the longer term (up to a median of ≈ 5 years). Onasemnogene abeparvovec was also associated with rapid age-appropriate achievement of motor milestones and improvements in motor function in children with pre-symptomatic SMA, indicating the benefit of early treatment. Onasemnogene abeparvovec was generally well tolerated. Hepatotoxicity is a known risk that can generally be mitigated with prophylactic prednisolone. In conclusion, onasemnogene abeparvovec represents an important treatment option for patients with SMA, particularly when initiated early in the course of the disease.
Spinal muscular atrophy (SMA) is a rare genetic condition that causes muscle weakness and wasting. Infants with SMA type 1, the most common form of the disease, are unable to sit without support and usually die before the age of 2 years if untreated. SMA is caused by a defect in the survival motor neuron 1 (SMN1) gene. This gene provides instructions for making survival motor neuron protein, which is essential for the health and normal function of the nerves that control muscles. Onasemnogene abeparvovec (Zolgensma®) is a gene therapy that replaces the missing SMN1 gene and is given as a one-time infusion into a vein. In patients with SMA, onasemnogene abeparvovec improved event-free survival (alive without breathing support), motor function and achievement of motor milestones. Patients maintained these improvements for up to ≈ 5 years after treatment. Onasemnogene abeparvovec also helped pre-symptomatic children reach motor milestones at ages similar to healthy children. Onasemnogene abeparvovec is generally well tolerated and is an important treatment option for patients with SMA, including those who are yet to develop symptoms.
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