Adenoviral GDNF gene transfer enhances neurofunctional recovery after recurrent laryngeal nerve injury

• Published in: Gene therapy Vol. 13; no. 4; pp. 296 - 303
• Main Authors: ARAKI, K, SHIOTANI, A, WATABE, K, SAITO, K, MORO, K, OGAWA, K
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.02.2006
• Subjects: Adenoviridae - genetics; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Applied cell therapy and gene therapy; beta-Galactosidase - genetics; Biological and medical sciences; Biotechnology; Brain stem; Care and treatment; Electrophysiology; Fundamental and applied biological sciences. Psychology; Gene expression; Gene therapy; Genetic Therapy - methods; Genetic Vectors - administration & dosage; Genetic Vectors - genetics; Glial cell line-derived neurotrophic factor; Glial Cell Line-Derived Neurotrophic Factor - analysis; Glial Cell Line-Derived Neurotrophic Factor - genetics; Glial Cell Line-Derived Neurotrophic Factor - metabolism; Glial cells; Health aspects; Health. Pharmaceutical industry; Immunohistochemistry - methods; Industrial applications and implications. Economical aspects; Injection; Injections, Intralesional; Inoculation; Medical sciences; Motor Neurons - chemistry; Motor Neurons - metabolism; Motor Neurons - pathology; Myelination; Nerve conduction; Nervous system diseases; Neural Conduction; Neuronal-glial interactions; Nucleus ambiguus; Paralysis; Physiological aspects; Polymerase chain reaction; Rats; Rats, Sprague-Dawley; Recovery of function; Recurrent Laryngeal Nerve - metabolism; Recurrent Laryngeal Nerve Injuries; Reverse transcription; Risk factors; Transduction, Genetic - methods; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Vocal Cord Paralysis - etiology; Vocal Cord Paralysis - metabolism; Vocal Cord Paralysis - therapy; β-Galactosidase; Japan; Nucleus; Adenoviridae; Injury; cranial nerve injury; Recurrent; Genetic transfer; vocal fold palsy; Virus; GDNF; recurrent laryngeal nerve; adenovirus; Cranial nerve; nucleus ambiguus; Gene therapy; Vector
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3302665

To assess the possibility of gene therapy for recurrent laryngeal nerve (RLN) injury, we examined functional and histological recovery after glial cell line-derived neurotrophic factor (GDNF) gene transfer in a rat RLN crush model. Adenoviral vector encoding beta-galactosidase gene (AxCALacZ) or human GDNF gene (AxCAhGDNF) was injected into the crush site of the RLN. Neurons in the nucleus ambiguus on the crushed side were labeled with X-gal or GDNF immnohistochemistry after AxCALacZ or AxCAhGDNF injection. Reverse transcription-polymerase chain reaction analysis revealed expression of human GDNF mRNA transcripts in brainstem tissue containing the nucleus ambiguus on the crushed side after AxCAhGDNF injection. Animals injected with AxCAhGDNF displayed significantly improved motor nerve conduction velocity of the RLN and recovery rate of vocal fold movement at 2 and 4 weeks after treatment as compared to controls. AxCAhGDNF-injected animals showed a significantly larger axonal diameter and improved remyelination in crushed RLN as compared to controls. Adenoviral GDNF gene transfer may thus promote laryngeal function recovery after RLN injury. Inoculation of adenoviral vector containing the GDNF gene at the site of damage soon after nerve injury may assist patients with laryngeal paralysis caused by nerve injury during head and neck surgery.