Development of targeting therapy for sporadic ALS using RNA aptamers

2015 Fiscal Year Final Research Report

• Project/Area Number: 26640036
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: The University of Tokyo
• Principal Investigator: Kwak Shin 東京大学, 医学(系)研究科(研究院), 研究員 (40160981)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 脳神経疾患 / 神経科学 / 核酸

Outline of Final Research Achievements

Expression of abnormally calcium-permeable AMPA receptors that have Q/R site-unedited GluA2 subunit in their subunit assembly in the motor neurons is involved in the pathogenesis of sporadic ALS. We explored the possibility of stable RNA aptamers that effectively blocked Ca2+-permeable AMPA receptors as a drug for ALS using a mechanistic ALS mouse model. Using a subcutaneously placed mini-pump, the RNA aptamer was continuously infused intracerebroventricularly through an indwelling cannula. The RNA aptamer was safely delivered to brains and spinal cords without extensive degradation and effectively blocked abnormal Ca2+ influx into the cortical and spinal cord neurons. AMPA receptor-specific RNA aptamers may be a potential drug for ALS.

Free Research Field

総合生物