History of development of the life-saving drug "Nusinersen" in spinal muscular atrophy

Jiaying Qiu; Liucheng Wu; Ruobing Qu; Tao Jiang; Jialin Bai; Lei Sheng; Pengchao Feng; Junjie Sun

doi:10.3389/fncel.2022.942976

History of development of the life-saving drug "Nusinersen" in spinal muscular atrophy

Front Cell Neurosci. 2022 Aug 12:16:942976. doi: 10.3389/fncel.2022.942976. eCollection 2022.

Authors

Jiaying Qiu^{1

2}, Liucheng Wu³, Ruobing Qu⁴, Tao Jiang⁵, Jialin Bai⁶, Lei Sheng⁷, Pengchao Feng⁸, Junjie Sun¹

Affiliations

¹ Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong, China.
² Department of Prenatal Screening and Diagnosis Center, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, China.
³ Laboratory Animal Center, Nantong University, Nantong, China.
⁴ Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, China.
⁵ Institute of Neuroscience, Soochow University, Suzhou, China.
⁶ College of Life Sciences, Nanjing Normal University, Nanjing, China.
⁷ Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, China.
⁸ Nanjing Antisense Biopharmaceutical Co., Ltd, Nanjing, China.

Abstract

Spinal muscular atrophy (SMA) is an autosomal recessive disorder with an incidence of 1/6,000-1/10,000 and is the leading fatal disease among infants. Previously, there was no effective treatment for SMA. The first effective drug, nusinersen, was approved by the US FDA in December 2016, providing hope to SMA patients worldwide. The drug was introduced in the European Union in 2017 and China in 2019 and has so far saved the lives of several patients in most parts of the world. Nusinersen are fixed sequence antisense oligonucleotides with special chemical modifications. The development of nusinersen progressed through major scientific discoveries in medicine, genetics, biology, and other disciplines, wherein several scientists have made substantial contributions. In this article, we will briefly describe the pathogenesis and therapeutic strategies of SMA, summarize the timeline of important scientific findings during the development of nusinersen in a detailed, scientific, and objective manner, and finally discuss the implications of the development of nusinersen for SMA research.

Keywords: SMN1/2; antisense oligonucleotide; nusinersen; spinal muscular atrophy; splicing regulation.

Publication types

Review