Intrathecal injection of HVJ-E containing HGF gene to cerebrospinal fluid can prevent and ameliorate hearing impairment in rats.
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.
Oshima
Kazuo
K
Division of Gene Therapy Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Shimamura
Munehisa
M
Mizuno
Shinya
S
Tamai
Katsuto
K
Doi
Katsumi
K
Morishita
Ryuichi
R
Nakamura
Toshikazu
T
Kubo
Takeshi
T
Kaneda
Yasufumi
Y
D000818:Animals; D002555:Cerebrospinal Fluid; D007758:Ear, Inner; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage; D034381:Hearing Loss / Q000139:chemically induced / Q000517:prevention & control / Q000628:therapy*; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D007278:Injections, Spinal; D007612:Kanamycin; D051381:Rats; D029082:Sendai virus / Q000235:genetics*; D013346:Subarachnoid Space; D014162:Transfection
D007612:Kanamycin; D017228:Hepatocyte Growth Factor