2004 Fiscal Year Final Research Report Summary
Basic study for the gene therapy of the peripheral motor nerve paralysis
| Project/Area Number |
15591831
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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 |
SHIOIANI Akihiro Keio University, Department of Medicine, Dept. of Otolaryngology, Assistant Professor, MD, 医学部, 専任講師 (80215946)
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| Project Period (FY) |
2003 – 2004
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| Keywords | laryngeal paralysis / gene therapy / nucleus ambiguus / adenovirus vector / nerve crush / functional recovery |
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| Research Abstract |
For the development of the human gene therapy for laryngeal paralysis, the therapeutic effects of gene transfer into the following parts were investigated in rat laryngeal paralysis model : denervated rat laryngeal muscle, rat nucleus ambiguus after vagal avulsion, and rat recurrent laryngeal nerve fiber injured by being crushed.
Four weeks after IGF-I gene transfer into denervated rat laryngeal muscle, IGF-I transfected animals had a significant improvement in muscle fiber diameter and motor endplate morphology.
Two and four weeks after GDNF gene transfer into rat nucleus ambiguus after vagal avulsion, GDNF gene transfected animals had a significantly larger number of surviving motor neurons. Simultaneous BDNF gene transfer enhanced these neuroprotective effects of GDNF gene transfer.
Two and four weeks after GDNF gene transfer into crush injured rat recurrent laryngeal nerve fiber, significantly faster nerve conduction velocity and better vocal fold motion recovery were observed in GDNF gene transfected animals.
These results indicate that gene therapy for laryngeal paralysis may provide tremendous opportunity for the augmentation of current surgical treatment modalities or even eliminate the need for surgical treatment.
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