Adenoviral gene transfer of aspartoacylase into the tremor rat, a genetic model of epilepsy, as a trial of gene therapy for inherited epileptic disorder
2002; Elsevier BV; Volume: 328; Issue: 3 Linguagem: Inglês
10.1016/s0304-3940(02)00522-0
ISSN1872-7972
AutoresTakahiro Seki, Hiroaki Matsubayashi, Taku Amano, Kazuhiro Kitada, Tadao Serikawa, Norio Sakai, Masashi Sasa,
Tópico(s)Neurological disorders and treatments
ResumoThe tremor rat (tm/tm) is a genetic model of epilepsy that exhibits absence-like seizures characterized by 5–7 Hz spike–wave-like complexes in cortical and hippocampal electroencephalograms (EEGs). A deletion of the aspartoacylase (ASPA) gene and resultant high levels of N-acetyl-aspartate (NAA) in the brain have been found in tremor rats. We attempted to determine whether gene transfer of ASPA inhibited absence-like seizures in tremor rats using recombinant adenovirus. Recombinant adenovirus (5×107 pfu) carrying the rat ASPA gene (AxASPA) or β-galactosidase gene (AxLacZ), as a control virus, was intracerebroventricularly administered to premature tremor rats aged 7 weeks. Cortical and hippocampal EEG were recorded with chronically implanted electrodes before and after viral administration. The absence-like seizures were increased in AxLacZ-administered control rats with age. However, the increase was significantly inhibited in AxASPA-administered rats at 1 week after treatment. These results suggest that gene transfer of ASPA is effective in inhibiting the generation of absence-like seizures, probably by reducing the NAA level.
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