| Project/Area Number |
18K16751
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | Kindai University |
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Principal Investigator |
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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 |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 脊髄損傷マウス / 下部尿路機能障害 / TRP channel / ウイルスベクター / β３アゴニスト / laser microdissection / 膀胱求心路 / 脊髄後根神経節 / β3 agonist / Laser Microdissection / 脊髄損傷 / 排尿筋過活動 / TRPV1 / 後根神経根 |
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| Outline of Final Research Achievements |
SCI induces detrusor overactivity (DO), which is mediated by spinal reflexes triggered by hyperexcitable C-fiber afferent pathways. It has also been reported that TRPV1 receptors predominantly expressed in C-fibre afferent pathways greatly contribute to DO in SCI. However, the clinical application of TRPV1 antagonists for chronic pain has been hampered partly due to their adverse events such as hyperthermia. Hence, the development of local therapies that can target TRPV1 receptors expressed in the affected organs and their afferent pathways without inducing systemic adverse events would be useful for the treatment of DO in SCI. This study investigated the effect of HSV vectors-mediated gene delivery of non-functional, poreless TRPV1 or PP1α in storage and voiding dysfunction using SCI mice. Gene therapy with HSV vectors encoding poreless TRPV1 or PP1α could be a novel treatment that can avoid systemic adverse events for hypersensitive bladder disorders such as SCI.
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| Academic Significance and Societal Importance of the Research Achievements |
脊髄損傷の発生数は、日本では高齢者の脊髄損傷の発生率が欧米に比較し多いと言われている。脊髄を損傷した後は、排泄ができない期間があり、その後不随意収縮にて頻尿が発生し、尿失禁が引き起こされる。このことは生活の質をかなり低下させる。よって脊髄損傷に伴う膀胱機能障害の病態機序の解明、ならびに治療法の開発は急務である。複製欠損単純ヘルペスウイルスベクターを用いた手法で脊髄損傷マウスの脊髄での病理学的診断かつ治療法へ試みたのは我々が初めてであり、さらに治療薬の開発に向けて研究を進める価値があると考え今回の研究を行った。結果、新規ウイルスベクターを用いた新しい手法は、新規治療方法となりうる事が示唆された。
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