Portal de Periódicos da CAPES

IGF-1 Gene Transfer Into Denervated Rat Laryngeal Muscle

1999; American Medical Association; Volume: 125; Issue: 3 Linguagem: Inglês

10.1001/archotol.125.3.274

1538-361X

Paul W. Flint, Akihiro Shiotani, Bert W. O’Malley,

Voice and Speech Disorders

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 ani-mals 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.