Clearing the pathology of the SCA36 multiple system disturbance

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15373
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Jichi Medical University
• Principal Investigator: Matsuzono Kosuke 自治医科大学, 医学部, 助教 (80809070)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: iPS細胞 / 神経難病 / 脊髄小脳変性症

Outline of Final Research Achievements

We studied with the induced pluripotent stem cell (iPSC) derived from spinocerebellar ataxia type 36 (SCA36). We differentiated SCA36-iPSCs to motor neuron cells, cortex neuron cells, and dopaminergic cells, which revealed NOP56 expression decrease. From these SCA36-iPSCs study, we cleared that the NOP56 gene expression decrease universally concerns with the SCA36 multiple system disturbance.
Next we produced the novel gene transgenic mice, NOP56 knockout mice. Surprisingly, NOP56 completely knockout mice died within 7 days from born. Thus, we studied the NOP56 hetero-knockdown mice behavior test. In results, NOP56 hetero-knockdown mice showed the cerebellar disturbance, which suggests that SCA36 patient cerebellar ataxia concerns with the NOP56 50% expression decrease.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

日本で確認されたSCA36患者は年々増加しているが、SCA36では原因遺伝子がNOP56内のGGCCTGリピートの延長であること、脊髄小脳変性症の病型に加え、筋萎縮性側索硬化症に類似した病態を呈すること等が分かっている。しかし、SCA36の多系統の神経障害は分かっていなかった。本研究でSCA36の主病態である小脳障害が原因遺伝子のNOP56の発現低下であることが分かったことで、今後NOP56の発現を増加させる薬物をSCA36患者に投与することで病態を改善させる、創薬につながることが期待される。