2023 Fiscal Year Final Research Report
Splicing dynamics of vasoactive factors in muscular dystrophy and therapeutic application in muscular dystrophy
| Project/Area Number |
20K08243
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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 52050:Embryonic medicine and pediatrics-related
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
李 知子 兵庫医科大学, 医学部, 准教授 (10596042)
下村 英毅 兵庫医科大学, 医学部, 准教授 (30441273)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | 筋ジストロフィー / スプライシング / 血管作動性因子 / アンチセンスオリゴヌクレオチド |
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| Outline of Final Research Achievements |
The splicing isoforms of vasoactive factors such as vascular endothelial growth factor (VEGF) and VEGF receptor may be involved in the pathogenesis of Duchenne muscular dystrophy (DMD). We established a VEGF-A splicing isoform analysis system with the aim of investigating the possibility of treatment by controlling splicing with an antisense oligonucleotide (AS-oligo). In addition, we found that the modified nucleic acids, 2'-O,4'-C-ethylene-bridged nucleic acids (ENAs), have better uptake in biological tissues than other modified nucleic acids, and also revealed the natural history of motor, respiratory, and cardiac functions in DMD.
Although we were unable to fully examine the relationship between the splicing isoforms of vasoactive factors and the course of clinical symptoms in individual cases, the splicing isoform analysis system established in this study is expected to clarify the relationship between the splicing type and the clinical course in each DMD case in the future.
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| Free Research Field |
小児科学
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| Academic Significance and Societal Importance of the Research Achievements |
DMD症例の運動・呼吸・心機能などの自然歴を明らかにした。個々の症例における臨床症状の経過と血管作動性因子のスプライシングアイソフォームとの関連を十分に検討するには至らなかったが、本研究で確立したスプライシングアイソフォーム解析システムにより、今後、DMD症例ごとのスプライシング型と臨床経過の関連を解明することにより、血管作動性因子の病態への関与が明らかになることが期待される、また、修飾核酸ENAの有用性を明らかにできたことにより、AS-oligoによる血管作動性因子のスプライシング型を制御する治療の検討を、大きく促進することが可能となる。
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