Nusinersen: A Review in 5q Spinal Muscular Atrophy

Funding The preparation of this review was not supported by any external funding.

Authorship and Conflict of interest Sheridan M. Hoy is a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

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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. 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 (administered intrathecally) 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 ≈ 6 years), 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.

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