Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder caused by mutations in the survival of motor neuron 1 (SMN1) gene, which leads to a reduced level in the SMN protein within cells. Patients with SMA suffer from a loss of alpha motor neurons in the spinal cord leading to skeletal muscle atrophy in addition to deficits in other tissues and organs. Patients with severe forms of the disease require ventilator assistance and typically succumb to the disease due to respiratory failure. Onasemnogene abeparvovec is an adeno-associated virus (AAV)-based gene therapeutic that has been approved for infants and young children with SMA, and it is delivered through intravenous administration using a dose based on the weight of the patient. While excellent outcomes have been observed in treated patients, the greater viral dose necessary to treat older children and adults raises legitimate safety concerns. Recently, onasemnogene abeparvovec use was investigated in older children through a fixed dose and intrathecal administration, a route that provides a more direct delivery to affected cells in the spinal cord and central nervous system. The promising results observed in the STRONG trial may support approval of onasemnogene abeparvovec for a greater proportion of patients with SMA.
Keywords: gene therapy; motor neuron disease; neuromuscular disease; onasemnogene abeparvovec; spinal muscular atrophy.