2002 Fiscal Year Final Research Report Summary
Gene Therapy for Peripheral Motor Nerve Paralysis
| Project/Area Number |
13671799
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Keio University |
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Principal Investigator |
SHIOTANI Akihiro MD, Keio University, School of Medicine, Department of Otolaryngology, Assistant Professor, 医学部, 専任講師 (80215946)
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| Co-Investigator(Kenkyū-buntansha) |
MORO Kazuhisa MD, Keio University, School of Medicine, Department of Otolaryngology, Instructor, 医学部, 助手 (30317226)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Laryngeal paralysis / Motor nerve paralysis / Gene therapy / Adenovirus / Nucleus ambiguus / Motor neuron loss / GDNF / Recurrent laryngeal nerve |
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| Research Abstract |
We examined neuroprotective effects of an adenoviral vector encoding glial cell line-derived neurotrophic factor (AxCAhGDNF) on the lesioned adult rat motoneurons in the nucleus ambiguus. After vagal nerve avulsion, AxCAhGDNF, AxCALacZ (adenovirus encoding b-galactosidase gene) or PBS was inoculated into the jugular foramen. Four days after the avulsion and treatment with AxCALacZ, the animals expressed b-galactosidase activity in the lesioned motoneurons in the nucleus ambiguus. The animals avulsed and inoculated with AxCAhGDNF showed immunolabeling for GDNF in the nucleus ambiguus on the treated side and expression of virus-induced human GDNF mRNA transcripts in the brainstem tissue that contained the nucleus ambiguus of the treated side. The treatment with AxCAhGDNF after avulsion prevented the loss of lesioned motoneurons in the nucleus ambiguus, amelliorated the choline acetyltransferase immunoreactivity, and also suppressed the activity of nitric oxide synthase in these neurons. These results indicate that adenovirus-mediated GDNF gene transfer may prevent the degeneration of motoneurons in humans after either vagal nerve injury orrecurrent laryngeal nerve injury
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[Publications] Koichiro,Saito, Akihiro,Shiotani, Kazuhiko,Watabe, Kazuhisa,Moro, Hiroyuki,Fukuda, Kaoru,Ogawa: "A denoviral GDNF gene transfer prevents motoneuron loss in the nucleus ambiguus"Brain Research. 962. 61-67 (2003)
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