| Project/Area Number |
18K08043
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Nara Medical University |
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Principal Investigator |
Onoue Kenji 奈良県立医科大学, 医学部, 学内講師 (90510173)
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| Co-Investigator(Kenkyū-buntansha) |
位高 啓史 東京医科歯科大学, 生体材料工学研究所, 教授 (60292926)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 特発性心筋症 / 核酸医薬 / 原因療法 / 遺伝性疾患 / 遺伝性心筋症 / 核酸医療 / 蓄積病 / 核酸医療薬 / 心筋疾患 |
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| Outline of Final Research Achievements |
The pathogenesis of myocardial diseases such as idiopathic cardiomyopathy has been gradually elucidated. On the other hand, only symptomatic treatment is available, and the development of a causative therapy is desired. The aim of this study was to develop a causative therapy that replenishes normal proteins that are lacking due to genetic abnormalities using nucleic acids, and to establish a nucleic acid medicine that can be applied clinically.
We tested the therapeutic effect of wild-type lamin mRNA by administering it immediately after birth to lamin (Lmna) gene knockout mice with dilated cardiomyopathy. However, effective delivery to the heart could not be achieved by this method, so we changed to AAV-based delivery. As a result, the Lamin-expressing group showed prolonged survival and improved cardiac function compared to the control.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、遺伝性心筋症や蓄積病といった心筋疾患を呈するマウスモデルを対象に、遺伝子異常により不足している正常蛋白質を核酸により補充するという新たな原因療法を開発することを目的とした。すなわち特発性心筋症をはじめとした心筋疾患治療において新たな臨床応用可能な核酸医療薬を確立することである。現時点では有望な結果が得られ、さらに臨床応用可能なデリバリーや投与形態を模索中である。これらが完成すれば、本研究の成果は今後の心筋症診療のみならず、全ての遺伝性疾患の診療に応用でき、新たな原因療法となりうる。多くの患者治療に変革をもたらし得る非常に重要な研究になると考える。
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