Dissection of the pathomechanisms of motor neuron disease using antisense therapeutics

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461268
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Nagoya University
• Principal Investigator: Sahashi Kentaro 名古屋大学, 医学部附属病院, 病院助教 (90710103)
• Co-Investigator(Renkei-kenkyūsha): OKADA Yohei 愛知医科大学, 医学部, 特任准教授 (30383714)
• Research Collaborator: Bennett C. Frank Ionis Pharmaceuticals, Senior Vice President
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 球脊髄性筋萎縮症 / 運動ニューロン疾患 / アンチセンス核酸

Outline of Final Research Achievements

Spinal and bulbar muscular atrophy or SBMA results from mutations in the AR gene and elicits motor deficits due to lower motor neuron and muscle degeneration. Toxicity of abnormal AR protein causes SBMA, but the primary pathogenic region remains elusive. Antisense oligonucleotides (ASOs) can control gene expression and contribute to identification of the target for the development of therapeutics. Here we have found that an intracerebroventricular injection of ASOs suppressing AR expression in the central nervous system, improves motor function, weight gain and survival with the amelioration of neuronal histopathology in an SBMA mouse model, focusing the neurotoxicity of mutant AR as a therapeutic target. This study further supports the applicability of antisense therapeutics for SBMA.

Free Research Field

運動ニューロン疾患