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Intrathecal injection of HVJ‐E containing HGF gene to cerebrospinal fluid can prevent and ameliorate hearing impairment in rats
Author(s) -
Oshima Kazuo,
Shimamura Munehisa,
Mizuno Shinya,
Tamai Katsuto,
Doi Katsumi,
Morishita Ryuichi,
Nakamura Toshikazu,
Kubo Takeshi,
Kaneda Yasufumi
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0567fje
Subject(s) - spiral ganglion , hepatocyte growth factor , inner ear , auditory brainstem response , medicine , cisterna magna , genetic enhancement , viral vector , cerebrospinal fluid , cochlea , immunology , pathology , pharmacology , cancer research , hearing loss , gene , biology , audiology , anatomy , receptor , genetics , recombinant dna
Hearing impairment, which is the most prevalent sensory deficit of human beings, needs a breakthrough in therapeutic technologies. One technology is the usage of a vector system to reach the inner ear, and another is by a therapeutic molecule. Here we developed a novel gene therapy strategy by combining hepatocyte growth factor (HGF) with hemagglutinating virus of Japan envelope (HVJ‐E) vector. When HVJ‐E containing human HGF gene was injected intrathecally into the cerebrospinal fluid via cisterna magna of rats, the vector reached the inner ear region, and human HGF gene expression was detected in the spiral ganglion cells (SGCs) of the inner ear. Expression of endogenous rat HGF and its receptor, c‐Met, was also induced in SGCs by human HGF. Kanamycin treatment results in hearing impairment by inducing degeneration of hair cells (HCs) and apoptosis of SGCs in rats. By HGF gene transfer before kanamycin treatment, both loss of HCs and apoptosis of SGCs were prevented. Furthermore, hearing function, evaluated by auditory brainstem response, was maintained at a normal level. When HGF gene transfer was performed 2 wk after kanamycin treatment, hearing impairment was significantly recovered. These results indicate a novel and effective therapeutic strategy against sensorineural hearing impairment.