Attempts to improve dystonia by regulating inhibitory neurotransmitter with overexpression of GAD65 and VGAT

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09328
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: University of the Ryukyus
• Principal Investigator: Fuchigami Tatsuya 琉球大学, 病院, 講師 (10381211)
• Co-Investigator(Kenkyū-buntansha): 神里 興太 琉球大学, 医学(系)研究科(研究院), 助教 (10554454)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 抑制性神経伝達物質

Outline of Final Research Achievements

The aim of the study was to "evaluate the utility of increasing the production and release of inhibitory neurotransmitters in the cerebellum and spinal cord as a novel treatment for dystonia. The sub-pial injection method can deliver the target genes (glutamate decarboxylase 65 and vesicular GABA transporter) to the cervical spinal cord. In this application, an animal model of dystonia was used to explore a novel treatment for systemic dystonia. In this study, we investigated the use of adeno-associated virus. Targeting treatment by gene transfer, we decided to investigate the effect of overexpression of GAD65 and VGAT on improvement of involuntary movements. We succeeded in introducing two different genes at the one time (single injection). However, no improvement in dystonia movement could be obtained.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

軟膜下投与法を使用し、２つの異なる遺伝子を一度に脊髄運動神経に導入することに成功した。これまで静脈注入法・実質内投与法と比較して、静脈投与よりも高効率で実質内投与よりも低侵襲でありながら、安全な遺伝子導入が実施できた．２つの全く異なる遺伝子導入が実践できたことから、「異常遺伝子の抑制」と「正常遺伝子の導入」ということが新たに可能であることが示された．より複雑な病態へ対応できる可能性が示された．