1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Nusinersen: A Review in 5q Spinal Muscular Atrophy

      research-article
      CNS Drugs
      Springer International Publishing

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Plain Language Summary

          5q spinal muscular atrophy (SMA) is a rare disease most commonly caused by a defect in the survival motor neuron ( SMN1 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.

          Related collections

          Most cited references50

          • Record: found
          • Abstract: found
          • Article: not found

          Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy

          New England Journal of Medicine, 377(18), 1723-1732
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy

            Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA).
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study.

              Nusinersen is a 2'-O-methoxyethyl phosphorothioate-modified antisense drug being developed to treat spinal muscular atrophy. Nusinersen is specifically designed to alter splicing of SMN2 pre-mRNA and thus increase the amount of functional survival motor neuron (SMN) protein that is deficient in patients with spinal muscular atrophy.
                Bookmark

                Author and article information

                Contributors
                demail@springer.com
                Journal
                CNS Drugs
                CNS Drugs
                CNS Drugs
                Springer International Publishing (Cham )
                1172-7047
                1179-1934
                30 November 2021
                30 November 2021
                2021
                : 35
                : 12
                : 1317-1328
                Affiliations
                GRID grid.420067.7, ISNI 0000 0004 0372 1209, Springer Nature, ; Private Bag 65901, Mairangi Bay, Auckland, 0754 New Zealand
                Article
                878
                10.1007/s40263-021-00878-x
                8709816
                34850360
                c6e15231-e061-4d96-8f3a-353f8d36af4c
                © Springer Nature 2021, corrected publication 2021

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                Categories
                Adis Drug Evaluation
                Custom metadata
                © Springer Nature Switzerland AG 2021

                Comments

                Comment on this article