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[Pharmacological and clinical profile of spinal muscular atrophy (SMA) therapeutic drug nusinersen (Spinraza®)].
Nihon Yakurigaku Zasshi 2018; 152(3):147-159NY

Abstract

Nusinersen (Spinraza®) was approved as Japan's first antisense oligonucleotide (ASO) drug for treatment of SMA (spinal muscular atrophy) patients with a deletion or mutation of the survival motor neuron (SMN) 1 gene and ≥1 copy of the SMN2 gene. Nuseinersen is a fully modified 2'-O-(2-methoxyethyl) (2'-MOE) ASO designed to bind the SMN2 pre-mRNA and alter splicing, such that a mature mRNA is produced and is translated as full-length SMN protein. In 4 types of mouse SMA disease models, treatment with nusinersen improved the form of the neuromuscular junction, increased myofiber size, improved righting reflex and grip, and prolonged survival. The efficacy of nusinersen was verified in 2 multinational, randomized, double-blind, sham-controlled clinical studies in SMA patients with differing ages of onset and ages (ENDEAR study and CHERISH study), and improvement and maintenance of motor function by nusinersen were demonstrated regardless of the type of SMA. Moreover, both studies showed that greater efficacy may be obtained with early initiation of nusinersen treatment. Therefore, treatment with nusinersen should be started as early as possible to delay or halt progression of the disease and maximize therapeutic effect. As nusinersen is the only ASO currently available for SMA, it will be widely used, therefore we will expect that nusinersen will contribute to improve patients' QOL and reduce the burden of caregivers and the healthcare system by improving motor function of patients with SMA.

Authors+Show Affiliations

Drug Development Division, Biogen Japan Ltd.Drug Development Division, Biogen Japan Ltd.Medical, Biogen Japan Ltd.Medical, Biogen Japan Ltd.Drug Development Division, Biogen Japan Ltd.President and representative director, Biogen Japan Ltd.

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

jpn

PubMed ID

30185733

Citation

Ohmura, Tsuyoshi, et al. "[Pharmacological and Clinical Profile of Spinal Muscular Atrophy (SMA) Therapeutic Drug Nusinersen (Spinraza®)]." Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica, vol. 152, no. 3, 2018, pp. 147-159.
Ohmura T, Saeki S, Ogiwara K, et al. [Pharmacological and clinical profile of spinal muscular atrophy (SMA) therapeutic drug nusinersen (Spinraza®)]. Nippon Yakurigaku Zasshi. 2018;152(3):147-159.
Ohmura, T., Saeki, S., Ogiwara, K., Tobita, K., Ling, Y., & Torii, S. (2018). [Pharmacological and clinical profile of spinal muscular atrophy (SMA) therapeutic drug nusinersen (Spinraza®)]. Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica, 152(3), pp. 147-159. doi:10.1254/fpj.152.147.
Ohmura T, et al. [Pharmacological and Clinical Profile of Spinal Muscular Atrophy (SMA) Therapeutic Drug Nusinersen (Spinraza®)]. Nippon Yakurigaku Zasshi. 2018;152(3):147-159. PubMed PMID: 30185733.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Pharmacological and clinical profile of spinal muscular atrophy (SMA) therapeutic drug nusinersen (Spinraza®)]. AU - Ohmura,Tsuyoshi, AU - Saeki,Seiji, AU - Ogiwara,Kazutaka, AU - Tobita,Kimimasa, AU - Ling,Yan, AU - Torii,Shinichi, PY - 2018/9/7/entrez PY - 2018/9/7/pubmed PY - 2019/6/18/medline SP - 147 EP - 159 JF - Nihon yakurigaku zasshi. Folia pharmacologica Japonica JO - Nippon Yakurigaku Zasshi VL - 152 IS - 3 N2 - Nusinersen (Spinraza®) was approved as Japan's first antisense oligonucleotide (ASO) drug for treatment of SMA (spinal muscular atrophy) patients with a deletion or mutation of the survival motor neuron (SMN) 1 gene and ≥1 copy of the SMN2 gene. Nuseinersen is a fully modified 2'-O-(2-methoxyethyl) (2'-MOE) ASO designed to bind the SMN2 pre-mRNA and alter splicing, such that a mature mRNA is produced and is translated as full-length SMN protein. In 4 types of mouse SMA disease models, treatment with nusinersen improved the form of the neuromuscular junction, increased myofiber size, improved righting reflex and grip, and prolonged survival. The efficacy of nusinersen was verified in 2 multinational, randomized, double-blind, sham-controlled clinical studies in SMA patients with differing ages of onset and ages (ENDEAR study and CHERISH study), and improvement and maintenance of motor function by nusinersen were demonstrated regardless of the type of SMA. Moreover, both studies showed that greater efficacy may be obtained with early initiation of nusinersen treatment. Therefore, treatment with nusinersen should be started as early as possible to delay or halt progression of the disease and maximize therapeutic effect. As nusinersen is the only ASO currently available for SMA, it will be widely used, therefore we will expect that nusinersen will contribute to improve patients' QOL and reduce the burden of caregivers and the healthcare system by improving motor function of patients with SMA. SN - 0015-5691 UR - https://www.unboundmedicine.com/medline/citation/30185733/[Pharmacological_and_clinical_profile_of_spinal_muscular_atrophy__SMA__therapeutic_drug_nusinersen__Spinraza®_]_ L2 - https://dx.doi.org/10.1254/fpj.152.147 DB - PRIME DP - Unbound Medicine ER -