Gene Therapy for Peripheral Motor Nerve Paralysis

• Project/Area Number: 13671799
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Keio University
• Principal Investigator: SHIOTANI Akihiro MD, Keio University, School of Medicine, Department of Otolaryngology, Assistant Professor, 医学部, 専任講師 (80215946)
• Co-Investigator(Kenkyū-buntansha): MORO Kazuhisa MD, Keio University, School of Medicine, Department of Otolaryngology, Instructor, 医学部, 助手 (30317226)
• Project Period (FY): 2001 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥4,100,000 (Direct Cost: ¥4,100,000); Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
• Keywords: Laryngeal paralysis / Motor nerve paralysis / Gene therapy / Adenovirus / Nucleus ambiguus / Motor neuron loss / GDNF / Recurrent laryngeal nerve / adenovirus / 顔面神経麻痺 / アデノウイルス

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

Research Products

• [Publications] 塩谷 彰浩: "反回神経麻痺の遺伝子治療の研究"日気食会報. 53. 124-128 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 塩谷 彰浩: "声帯萎縮に対する遺伝子治療"音声言語医学. 43. 438-443 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Saito Koichiro: "Adenoviral GDNF gene transfer prevents motor neuron loss in the nucleus ambiguos"Brain Research. 962. 61-67 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Akihiro,Shiotani: "Gene therapy for laryngeal paralysis"J Jpn Bronchoesophagol Soc. 53. 124-128 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Akihiro,Shiotani: "Gene therapy for vocal fold atrophy"Jpn J Logoped Phoniatr. 43. 438-443 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [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)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 塩谷 彰浩: "反回神経麻痺の遺伝子治療の研究"日気食会報. 53. 124-128 (2002)
• [Publications] 塩谷 彰浩: "声帯萎縮に対する遺伝子治療"音声言語医学. 43. 438-443 (2002)
• [Publications] Saito Koichiro: "Adenoviral GDNF gene transfer prevents motor neuron loss in the nucleus amibiguus"Brain Research. 962. 61-67 (2003)
• [Publications] Saito K, Shiotani A, et al: "Adenoviral GDNF gene therapy prevents motoneuron loss after laryngeal nerve injury"Otolaryngol-Head Neck Surg. 125. 141-142 (2001)