2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Nusinersen treatment in adult patients with spinal muscular atrophy: a safety analysis of laboratory parameters

      research-article

      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

          Background

          Nusinersen is an intrathecally administered antisense oligonucleotide (ASO) that improves motor function in patients with spinal muscular atrophy (SMA). In addition to efficacy, the safety of a therapy is the decisive factor for the success of the treatment. For some ASOs, various organ toxicities have been described, such as thrombocytopenia, renal and liver impairment, or coagulation abnormalities. However, systematic data on laboratory parameters under treatment with nusinersen are mainly available from studies in infants and children. Therefore, our aim was to assess the safety of nusinersen therapy in adult SMA patients.

          Methods

          Laboratory data from 404 nusinersen injections performed in 50 adult patients with SMA type 2 and type 3 were retrospectively analyzed.

          Results

          The total observation period was 76.9 patient-years, and patients received up to 12 injections. Our data provides no new safety concerns. In cerebrospinal fluid (CSF), the mean white blood cell count and lactate remained stable over time. Total CSF protein increased by 2.9 mg/dL. No change in mean platelet count was observed under therapy. Only one patient showed sporadic mild thrombocytopenia. Coagulation parameters and inflammatory markers were stable. The mean creatinine level decreased by 0.09 mg/dL. Analysis of mean liver enzyme levels revealed no relevant changes during treatment.

          Conclusion

          Our data demonstrate a favorable safety profile of nusinersen therapy in adult SMA patients under longer-term “real-world” conditions. In particular, we found no evidence of clinically relevant platelet declines, coagulopathies, or renal or hepatic organ toxicities, which are common concerns with the use of ASOs.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s00415-021-10569-8.

          Related collections

          Most cited references42

          • 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: found

              Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis

              Hereditary transthyretin amyloidosis is caused by pathogenic single-nucleotide variants in the gene encoding transthyretin ( TTR) that induce transthyretin misfolding and systemic deposition of amyloid. Progressive amyloid accumulation leads to multiorgan dysfunction and death. Inotersen, a 2'- O-methoxyethyl-modified antisense oligonucleotide, inhibits hepatic production of transthyretin.
                Bookmark

                Author and article information

                Contributors
                tim.hagenacker@uk-essen.de
                Journal
                J Neurol
                J Neurol
                Journal of Neurology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0340-5354
                1432-1459
                25 April 2021
                25 April 2021
                2021
                : 268
                : 12
                : 4667-4679
                Affiliations
                [1 ]GRID grid.410718.b, ISNI 0000 0001 0262 7331, Department of Neurology, , University Hospital Essen, ; Hufelandstr. 55, 45147 Essen, Germany
                [2 ]GRID grid.410718.b, ISNI 0000 0001 0262 7331, Institute for Medical Informatics, Biometrics and Epidemiology, , University Hospital Essen, ; Essen, Germany
                [3 ]GRID grid.410718.b, ISNI 0000 0001 0262 7331, Department of Clinical Chemistry, , University Hospital Essen, ; Essen, Germany
                [4 ]GRID grid.410718.b, ISNI 0000 0001 0262 7331, Institute for Diagnostic and Interventional Radiology and Neuroradiology, , University Hospital Essen, ; Essen, Germany
                [5 ]GRID grid.410718.b, ISNI 0000 0001 0262 7331, Center for Translational and Behavioral Neuroscience, , University Hospital Essen, ; Essen, Germany
                Article
                10569
                10.1007/s00415-021-10569-8
                8563549
                33899154
                3aacecf1-9d26-4f96-a822-04808b74e15a
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits 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/4.0/.

                Funding
                Funded by: Universität Duisburg-Essen (3149)
                Categories
                Original Communication
                Custom metadata
                © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany 2021

                Neurology
                aso,platelets,kidney,liver,coagulation,toxicity,side effects
                Neurology
                aso, platelets, kidney, liver, coagulation, toxicity, side effects

                Comments

                Comment on this article