Survival motor neuron 1 ( SMN1), located on chromosome 5q, encodes the survival motor neuron (SMN) protein. A deletion or mutation in SMN1 results in a rare neuromuscular disorder: 5q spinal muscular atrophy (SMA). In such patients, SMN protein production relies solely on SMN2. Nusinersen (Spinraza ®) is a modified antisense oligonucleotide approved for the treatment of 5q SMA. Administered intrathecally, it modifies SMN2 pre-messenger RNA splicing, thereby increasing full-length SMN protein levels. Interim analyses from an ongoing phase II study suggest substantial clinical benefits with nusinersen initiation in presymptomatic patients. In phase III studies, nusinersen achieved significant and/or clinically relevant improvements in motor function in symptomatic patients with infantile- and later-onset 5q SMA, and significantly improved event-free survival and overall survival in patients with infantile-onset 5q SMA. Longer term (up to a median of ≈ 6 years of available data), motor function was maintained or improved in symptomatic patients. Nusinersen had a favourable safety profile in clinical studies in presymptomatic and symptomatic patients. Real-world experience supports the effectiveness, safety and tolerability of nusinersen in symptomatic patients of all ages. Thus, nusinersen remains an important treatment option among a broad range of 5q SMA patients.
5q spinal muscular atrophy (SMA) is a rare disease most commonly caused by a defect in the survival motor neuron ( SMN) 1 gene, which in a healthy individual produces a protein [spinal motor neuron (SMN) protein] critical to maintaining the nerves that control muscles. Individuals with 5q SMA do not produce this protein in sufficient levels, resulting in muscle weakness and wasting (including the muscles involved in general movement, breathing and swallowing), so increasing the amount of SMN protein by modifying a nearly identical, but low functioning, gene ( SMN2) is one way to treat the disease. Nusinersen (Spinraza ®) is a treatment that targets SMN2. It is administered via lumbar puncture and is approved for use in presymptomatic and symptomatic individuals with 5q SMA. In both groups of patients, nusinersen increases the amount of SMN protein necessary for the muscles and nerves to work normally, improving motor function. This benefit persists over the longer-term (up to a median of ≈ 6 years of available data), and is well tolerated. Nusinersen continues to be an important treatment option among a broad range of 5q SMA patients.