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IGF-1 Gene Transfer Into Denervated Rat Laryngeal Muscle
Paul W. Flint, MD;
Akihiro Shiotani, MD;
Bert W. O'Malley, Jr, MD
Arch Otolaryngol Head Neck Surg. 1999;125:274-279.
Objectives To demonstrate gene transfer in rat laryngeal muscle using a reporter gene,  -galactosidase, and a muscle-specific expression system containing the human IGF-1 (hIGF-1) gene sequence and to investigate the myotrophic and neurotrophic effects of hIGF-1 gene transfer in denervated rat laryngeal muscle.
Methods In 8 adult rats, a polyvinyl-based formulation containing -galactosidase DNA was injected into denervated thyroarytenoid muscle. Twelve animals were similarly administered a polyvinyl-based formulation containing a muscle-specific expression system and hIGF-1 DNA. Twelve animals were injected with isotonic sodium chloride solution, and all animals survived for 1 month. The production of -galactosidase and hIGF-1 was detected using immunohistochemical techniques. The effects of hIGF-1 on motor endplates and nerve sprouting were assessed using cholinesterase or silver staining and immunostaining for growth-associated protein (GAP-43).
Results -Galactosidase was detected in 7 of 8 animals by immunostaining, X-gal histochemical staining, or both. In frozen section specimens, hIGF-1 immunoreactivity was positive in 3 of 8 animals. In sequential sections, GAP-43 was localized to areas of hIGF-1 expression in 2 of the 3 hIGF-1–positive specimens. Increased nerve sprouting and motor endplate contact occurred in 2 of 4 animals treated with hIGF-1.
Conclusions Gene transfer into laryngeal muscle was demonstrated using a polyvinyl-based formulation containing a muscle-specific gene expression system. Preliminary findings indicate a positive effect on motor endplates, nerve sprouting, and the expression of GAP-43 in animals treated with the hIGF-1 vector. This study establishes a foundation for investigating hIGF-1 gene transfer as a novel treatment of laryngeal paralysis. Further studies are necessary to quantify myotrophic and neurotrophic effects and to establish therapeutic benefit.
From the Departments of Otolaryngology–Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Md (Drs Flint, Shiotani, and O'Malley), and Keio University School of Medicine, Tokyo, Japan (Dr Shiotani).
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