ハンチントン病の治療戦略

Strategic approach for the prevention of Huntington disease

ハンチントン病はポリグルタミン病のひとつであり，その病態は主にポリグルタミン病に共通する部分が解明されてきている。したがって，現在追求されてきている実験的治療法は，必ずしもハンチントン病特異的なものではない。その治療ターゲットは神経細胞死，ミトコンドリア障害，転写抑制，凝集体形成，異常遺伝子であり，その評価はハンチントン病モデルマウスを用いて行われている。本稿ではそれらの結果をまとめるとともに，今後の展望について検討した。

Recently, the experimental preventive therapies have been developed based on the pathomechanism of Huntington disease or polyglutamine diseases. Those are mainly targeted to neuronal cell death, mitochondrial dysfunction, transcriptional dysregulation, aggregate formation, and disease gene itself. The effects of those treatments were assayed using transgenic mouse R6/2 and some extension of lifespan was observed up to 25%. We have focused to find the inhibitory compound to aggregate formation and found trehalose as an effective compound at cellular and mouse level. We have also tried to inhibit the abnormal gene expression at mRNA level using siRNA of EGFP transduced by adenoassociated virus on our huntintin exon1+EGFP mouse. This treatment attenuated aggregation formation and the disease progression even after the onset of the disease, suggesting the siRNA treatment will be another therapy for polyglutamine diseases.