GENE REPLACEMENT THERAPY FOR SPINAL MUSCULAR ATROPHY: AN OVERVIEW OF ONASEMNOGENE ABEPARVOVEC

Spinal Muscular Atrophy is a rare autosomal recessive disorder marked by progressive degeneration of anterior horn cells in the spinal cord, leading to muscle weakness, hypotonia, and, in severe cases, respiratory failure. The condition arises due to mutations or deletions in the SMN1 gene, resulting in inadequate production of survival motor neuron (SMN) protein, which is essential for motor neuron maintenance and function. Zolgensma (onasemnogene abeparvovec) is an advanced gene replacement therapy developed to address the underlying genetic defect in SMA. It employs an adeno-associated virus serotype 9 (AAV9) vector to deliver a functional copy of the SMN1 gene to motor neurons, enabling sustained production of SMN protein following a single intravenous administration. This innovative approach targets the root cause of the disease rather than providing symptomatic relief. Clinical evidence indicates that early intervention with Zolgensma leads to substantial improvements in survival, motor milestone achievement, and overall functional outcomes, particularly in infants treated prior to the onset of significant symptoms. While the therapy demonstrates remarkable efficacy, its use is associated with considerations such as potential hepatotoxicity, immune-mediated responses, and the necessity for close clinical monitoring.