Spinal muscular atrophy (SMA) is a debilitating hereditary disease characterized by progressive muscle weakness and atrophy occurring due to loss of the motor neurons in the spinal cord. Motor neurons are responsible for receiving the nerve impulses transmitted from the brain to the spinal cord and then transmitting those impulses via the peripheral nerves to the muscle. It is a rare disease with an incidence of approximately 1 in 10,000 live births.

SMA is divided into subtypes based on age of onset, severity of the condition, and associated signs and symptoms. Among subtypes, there is a wide variability of symptoms and severity. Muscle weakness, inability to sit independently, lack of motor development, tremor of the fingers, absence of deep tendon reflexes, and frequent falling are some manifestations of SMA. The most common form of SMA is associated with mutations in the SMN1 gene located on chromosome 5, which results in decreased production of the survival of motor neuron (SMN) protein. The SMN protein is necessary for normal motor neurons to function. Neighboring SMN2 genes on chromosome 5 can modify the severity of SMA as they also produce some functional SMN protein. Diagnosis is confirmed with molecular genetic testing to detect the presence of mutations in the SMN1 gene; the number of copies of the SMN2 gene can also be determined using molecular genetic testing. Prognosis varies by the subtype of SMA, and lifespan varies even within a subtype based on severity, symptoms, and treatment response.

On December 23, 2016, Spinraza (nusinersen) became the first FDA-approved treatment for SMA in children and adults. The FDA granted fast track designation, priority review, and orphan drug designation for this therapy. Spinraza is an antisense oligonucleotide that targets a specific sequence in the intron downstream of exon 7 of the SMN2 transcript, and it has shown to increase exon 7 inclusion in SMN2 messenger ribonucleic acid transcripts and production of full-length SMN protein. The most common side effects observed in patients were upper respiratory infection, lower respiratory infection, and constipation.

The approval of Spinraza was based on data from a randomized clinical trial of 121 patients diagnosed with infantile-onset SMA before 6 months of age and who were less than 7 months of age at the time of their first dose. The percentage of patients with improvement in motor milestones was assessed in the trial. An interim analysis of 82 of 121 enrollees revealed that 40% of Spinraza patients achieved improvement in motor milestones, whereas none of the control patients did. Additionally, findings of open-label uncontrolled clinical studies were generally supportive of the clinical efficacy demonstrated in the controlled clinical trial in infantile-onset patients. There are several drugs being studied for SMA, each approaching the disease from various angles. Possible treatment targets consist of replacement or correction of the SMN1 gene, modulation of the SMN2 gene, neuroprotection of affected motor neurons, and muscle protection; with further research, additional treatment options for SMA may emerge.