2005 年 17 巻 2 号 p. 76-79
This study reports on the clinical application of gene therapy and oral administration of T-588 for laryngeal paralysis. The therapeutic effects of gene therapy in rat laryngeal paralysis studies have been demonstrated. Now, the development of a safe gene delivery system is the essential issue for realizing clinical application. Currently, we are investigating two gene delivery systems, Sendai virus vector and electroporation, for possible clinical use. Sendai virus (SeV), a negative strand RNA virus has no known pathogenicity to humans, and its strict cytoplasmic life cycle in mammalian cells may guarantee substantial safety for human gene therapy. We scrutinized the applicability and efficacy of Sev vectors expressing either LacZ or IGF-I in gene transfer into skeletal muscle tissue. Seven days after the intramuscular injection of LacZ/SeV, a large number of X-gal labeled myofibers were observed in the leg muscle of a rat. The introduction of IGF-I/SeV showed a significant increase in regenerating and split myofibers indicative of hypertrophy, and also an increase in the total number of myofibers. We also investigated the applicability of electroporation for gene transfer into rabbit laryngeal muscle tissue, using plasmid DNA expressing GEP. The laryngeal muscle were injected with the plasmid DNA and electric pulses were delivered. Five days after gene transfer, a large number of muscle fibers expressing GEP were observed. These results indicate that either SeV or electroporation may be used as a gene delivery system for human gene therapy for laryngeal paralysis. In addition to gene therapy, we are investigating whether orally administered T-588, a neuroprotective agent, can be applied as a novel drug therapy for laryngeal paralysis. T-588 showed neuroprotective effects in a rat vagal nerve avulsion model as well as improvement in neurofunction in a rat recurrent nerve-injured model. These results support the applicability of T-588 for the treatment of laryngeal paralysis.