The effects of viral vector encoding neurotrophin in a rat model of detrusor underacrivity

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11180
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Nagoya University
• Principal Investigator: Majima Tsuyoshi 名古屋大学, 医学部附属病院, 助教 (90625138)
• Co-Investigator(Kenkyū-buntansha): 宮川 世志幸 日本医科大学, 医学部, 講師 (90415604)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 排尿筋低活動 / 遺伝子治療 / ウイルスベクター

Outline of Final Research Achievements

We investigated the effects of viral vector encoding neurotrophin in a rat model of detrusor underactivity induced by pelvic nerve crush injury. We identified successful delivery of herpes simplex virus (HSV) vectors into dorsal root ganglions and pelvic ganglions, but not 6 serotypes of adeno-associated viral vectors (1, 2, 5, 6, 8, and 9). Rats treated by HSV vectors encoding NGF and BDNF showed significant better voiding efficiency and less post-void residual urine volume compared to control rats in cystometry. Muscle strip studies showed that contractile responses of detrusor obtained from rats treated by HSV vectors was significantly higher than those from control rats. Immunohistochemistry indicated that the expressions of NGF and BDNF in dorsal root ganglions and pelvic ganglions were significantly higher in rats treated by HSV vectors than control rats.

Free Research Field

泌尿器科

Academic Significance and Societal Importance of the Research Achievements

排尿筋低活動は、排尿筋や膀胱支配神経（大脳、脳幹、脊髄、自律神経）を含む排尿機構に障害が生じることにより、十分な尿排出ができなくなる病態である。有効な治療法がないため、重度の患者は間欠的導尿や尿道カテーテル管理を余技なくされる。尿路感染症や腎後性腎不全などの重篤な合併症をも来し得る難治性疾患である。我々の開発したウイルスベクターは、根本的な治療法が存在しない難治性疾患である本病態に、全く新しい治療戦略をもたらす可能性が示唆された。また排尿筋低活動における新たな病態解明の糸口となる可能性も示された。