Autophagy-regulating microRNAs in Pompe disease and their therapeutic strategy

• Project/Area Number: 18K08472
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Fukuda Tokiko 浜松医科大学, 医学部, 特任教授 (10458268)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Pompe病 / マイクロRNA / AUTOPHAGY / ポンペ病 / バイオマーカー / バイオマーカーバイオマーカー / miRNA / オートファジ― / microRNA

Outline of Final Research Achievements

The results of microRNA expression analysis of human Pompe disease skeletal muscle were compared with other muscle glycogen storage disease. The authors have previously reported that autophagy is impaired in Pompe disease, forming a pathology that influences disease progression. miR-499a-5p, miR-206 and miR-208b-3p expression was reduced to approximately 40% in Pompe disease. miR-206 expression is increased, but miR-206 was not increased in glycogen storage disease type V as in Pompe disease.
MicroRNA-128, which reduces TFEB expression and autophagy function, was reduced by microRNA-128-3p to 40% in skeletal muscle in Pompe disease but not in glycogen storage disease type V, suggesting a different effect on autophagy.

Academic Significance and Societal Importance of the Research Achievements

autophagyに関与する遺伝子を制御するmiR-128、 miR-30aなどのmicroRNAのPompe病骨格筋における役割を明らかにすること。microRNAの調節による病態の改善および治療効果の改善の可能性を明らかにすることである。実臨床において、酵素補充療法や基質合成阻害薬、遺伝子治療の開発が行われており、Pompe病におけるmicroRNAの変化を明らかにすることによりautophagyの治療による改善の評価方法を見いだす可能性がある。