2023 Fiscal Year Final Research Report
Development of treatment for autism spectrum disorder relating with oxytocin and miRNA
| Project/Area Number |
19K08258
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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 | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2024-03-31
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| Keywords | 自閉スペクトラム症 / オキシトシン / MECP2重複症候群 / Rett症候群 / miRNA / AAV9 |
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| Outline of Final Research Achievements |
To develop the treatment for neurodevelopmental disorder, double blind test of a functional oligosaccharide that activate oxytocin nervous system to patients with autism spectrum disorder has been performed. So far, adverse events have not observed. After confirming the effects for neuronal function, we will move on to clinical trial.
Four miRNAs were identified to decrease the expression of MECP2 to the level about 60-84% in cultured neuronal cells from model mice hippocampus and also from human iPS cells. After the analysis of off target effects, we select the candidate miRNA to treat MECP2 duplication syndrome. Addition to them, AAV9 vector with MECP2 and SynI promotor that had low promotor activity was injected into cisterna magna of Rett syndrome model mice and improved phenotypes. After confirming these effects, we will plan the clinical trials.
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| Free Research Field |
小児神経学
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| Academic Significance and Societal Importance of the Research Achievements |
神経発達症の患者・家族の困難は多く、治療法が待たれている。機能性糖質の臨床研究で治療効果が示されれば、自閉スペクトラム症の治療確立に大きな進歩である。また、この機能性糖質は、オキシトシン神経系を賦活するため、オキシトシンと自閉症状の関連解明に重要な結果である。
神経発達症の症状を示す、MECP2関連疾患のMECP2重複症候群とRett症候群は、MECP2の厳密な発現コントロールが必要である。過剰発現を抑えるmiRNA、発現がないRett症候群患者への低発現プロモーターを用いた発現調節による治療開発は、これらの疾患の治療法ができることに加え、遺伝子治療での遺伝子発現調節に貴重な情報となる。
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