The Laryngoscope Lippincott Williams & Wilkins © 2008 The American Laryngological, Rhinological and Otological Society, Inc. Regeneration of Aged Vocal Fold: First Human Case Treated With Fibroblast Growth Factor Shigeru Hirano, MD, PhD; Yo Kishimoto, MD; Atsushi Suehiro, MD; Shin-ichi Kanemaru, MD, PhD; Juichi Ito, MD, PhD Background/Objectives: Aged vocal folds are characterized by atrophy of the mucosa, which causes dysphonia and is difficult to treat. We have revealed a therapeutic potential of basic fibroblast growth factor (bFGF) for tissue regeneration of the aged vocal fold. We report here the first human case that has been treated with bFGF. Study Design: Institutional review board approved clinical human trial. Methods: A 63-year-old man with atrophied vocal folds was treated by local injection of 10 g of bFGF into the left vocal fold under topical anesthesia. The effects of the injection were examined after 1 to 3 months by vid- eostroboscopy, acoustic and aerodynamic measurements. Results: The atrophy of the vocal fold was improved at 1 week after the injection and glottic gap disappeared. Aerodynamic and acoustic parameters also showed re- markable improvement. These positive effects were maintained up to 3 months. Conclusion: The first case with aged vocal folds treated with bFGF administration is presented. The re- sults are encouraging, suggesting therapeutic effects of bFGF for atrophied vocal folds in human. Key Words: Aged vocal fold, basic fibroblast growth factor, regeneration. Laryngoscope, 118:2254 –2259, 2008 INTRODUCTION Voice changes with age. It tends to become weak, harsh and breathy, especially in men. 1 This voice change is caused by the atrophy of the vocal fold which induces bowing, glottal insufficiency, and reduction of the mucosal traveling wave. 2,3 The atrophy occurs because of histolog- ical alterations of the lamina propria of the vocal fold, including excessive collagen deposition with formation of thick bundles, reduction of elastin and hyaluronic acid (HA). 4–7 It is required to address these histological changes to restore the aged vocal fold. Fibroblasts in the lamina propria are the main pro- vider of extracellular matrix (ECM). It has been revealed that fibroblasts decrease in number with age, and intra- cellular presence of golgi apparatus and rough endoplas- mic reticulum also decrease, which suggests reduction of activity to synthesize ECM. 8,9 Therefore, it may be impor- tant to activate fibroblasts and control their function of ECM production to produce sufficient HA and suppress excessive collagen synthesis. Basic fibroblast growth factor (bFGF) is a stimulant of growth of fibroblasts, and also induces modification of ECM production from the cells. In our previous in vitro study using aged rats has indicated that bFGF stimulates cell growth of fibroblasts in the aged vocal folds, and also induces a significant increase of HA production from those cells and suppresses production of collagen type I. 10 These effects seemed to be favorable for restoration of aged vocal fold lamina propria to younger state. The effects of local administration of bFGF into aged vocal folds were also examined in our subsequent in vivo study using aged rats. 11 The results showed a recovery of HA content in the lamina propria of aged vocal folds in the bFGF treated group, which suggested a therapeutic potential of bFGF to restore an appropriate viscoelasticity of the vocal folds. We then set up a protocol of use of bFGF for human cases with atrophied vocal folds caused by aging, which was approved by the institutional review board of Kyoto University. We re- port here the first human case treated by bFGF. MATERIALS AND METHODS Preparation of bFGF Product of bFGF solution usable for human (Fibrast) was developed by Kaken Pharmaceutical (Tokyo, Japan) using artifi- cial recombination of genes of human bFGF. Fibrast was From the Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Editor’s Note: This Manuscript was accepted for publication June 23, 2008. Presented at ALA annual meeting in Orlando, 2008. Send correspondence to Shigeru Hirano, MD, Department of Otolar- yngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan. E-mail: hirano@ent.kuhp. kyoto-u.ac.jp DOI: 10.1097/MLG.0b013e3181845720 Laryngoscope 118: December 2008 Hirano et al.: Regeneration of Aged Vocal Fold 2254