Development of spinal muscular atrophy treatment by SMN2 gene splicing modification

• Project/Area Number: 24791060
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Kobe University
• Principal Investigator: NAKAGAWA Taku 神戸大学, 医学部附属病院, 助教 (40457073)
• Co-Investigator(Renkei-kenkyūsha): NISHIO Hisahide 神戸大学, 大学院医学研究科, 教授 (80189258)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: spinal muscular atrophy / SMA / splicing / SMN2

Outline of Final Research Achievements

Spinal muscular atrophy is a fatal congenital neuromuscular disease caused by SMN1 gene mutation. Effective treatment has not established yet. As a strategy of the treatment, modification for SMN2 splicing is thought to be a promising approach. We previously discovered compound A is effective to modify the SMN2 splicing using mini gene system. Subsequently, we tried to search for similar compound that would modify the SMN2 splicing safely. However, we didn't find the effective compounds for SMN2 splicing correction during the study period.

Research Products

• [Journal Article] Somatic mosaicism of a CDKL5 mutation identified by next-generation sequencing (2015)
  • Author(s): Kato T, Morisada N, Nagase H, Nishiyama M, Toyoshima D, Nakagawa T, Maruyama A, Fu XJ, Nozu K, Wada H, Takada S, Iijima K.
  • Journal Title: Brain Dev. Volume: S0387-7604 Issue: 9 Pages: 64-69
  • DOI: 10.1016/j.braindev.2015.03.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Demographics and outcomes of patients with pediatric febrile convulsive status epilepticus (2015)
  • Author(s): Nishiyama M, Nagase H, Tanaka T, Fujita K, Maruyama A, Toyoshima D, Nakagawa T, Taniguchi-Ikeda M, Morioka I, Morisada N, Takada S, Iijima K.
  • Journal Title: Pediatr Neurol. Volume: 52 Issue: 5 Pages: 499-503
  • DOI: 10.1016/j.pediatrneurol.2015.02.001
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation (2013)
  • Author(s): Kato M, …Saitsu H.
  • Journal Title: Epilepsia Volume: in press Issue: 7 Pages: 1282-7
  • DOI: 10.1111/epi.12200
  • Peer Reviewed
• [Journal Article] A prostaglandin D2 metabolite is elevated in the urine of Duchenne muscular dystrophy patients and increases further from 8 years old. (2013)
  • Author(s): Nakagawa T, Takeuchi A, Kakiuchi R, Lee T, Yagi M, Awano H, Iijima K, Takeshima Y, Urade Y, Matsuo M.
  • Journal Title: Clin Chim Acta. Volume: 423 Pages: 10-14
  • DOI: 10.1016/j.cca.2013.03.031
  • Peer Reviewed
• [Journal Article] Acetaminophen administration in a patient with Gilbert's syndrome. (2012)
  • Author(s): Nakagawa T
  • Journal Title: Pediatr Int. Volume: 54 Issue: 6 Pages: 934-936
  • DOI: 10.1111/j.1442-200x.2012.03602.x
  • Peer Reviewed
• [Journal Article] Treatment of preterm infants with West syndrome: differences due to etiology. (2012)
  • Author(s): Mure T, Nakagawa T, Okizuka Y, Takami Y, Oyazato Y, Nagase H, Maruyama A, Adachi M, Takada S, Matsuo M.
  • Journal Title: Pediatr Int Volume: 6 Issue: 6 Pages: 892-8
  • DOI: 10.1111/j.1442-200x.2012.03708.x
  • Peer Reviewed
• [Journal Article] Paramyotonia congenita: From clinical diagnosis to in silico protein modeling analysis. (2012)
  • Author(s): Nurputra DK
  • Journal Title: Pediatr Int. Volume: 54 Issue: 5 Pages: 602-612
  • DOI: 10.1111/j.1442-200x.2012.03646.x
  • Peer Reviewed
• [Presentation] てんかん発作にビタミンB6製剤が著効した先天性GPI欠損症の一男児例 (2014)
  • Author(s): 中川卓, 西山将広, 豊嶋大作, 森貞直哉, 池田（谷口）真理子, 岡本伸彦, 村上良子, 高田哲, 飯島一誠
  • Organizer: 第48回日本てんかん学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-10-02 – 2014-10-03
• [Presentation] A prostaglandin D2 metabolite is elevated in the urine samples of patients with Duchenne muscular dystrophy. (2013)
  • Author(s): Nakagawa T, Takeuchi A, Kakiuchi R, Lee T, Yagi M, Awano H, Iijima K, Takeshima Y, Urade Y, Matsuo M.
  • Organizer: World Muscle Society 18th Congress
  • Place of Presentation: California, USA
• [Presentation] Duchenne型筋ジストロフィーにおける尿プロスタグランディンD2代謝産物の排泄の増加 (2012)
  • Author(s): 中川 卓, 李 知子, 粟野 宏之, 八木 麻理子, 松尾 雅文, 竹島 泰弘
  • Organizer: 第54回日本小児神経学会総会
  • Place of Presentation: 札幌