Neurological Surgery 脳神経外科34巻11号

2006年11月発行

連載 脳神経外科医療のtranslational research（1）

脳神経外科における疾患標的治療―分子標的治療と薬剤投与法―

著者： 齋藤竜太¹ 隈部俊宏¹ 冨永悌二¹

所属機関： ¹東北大学大学院医学系研究科神経外科学分野

ページ範囲：P.1157 - P.1165

Ⅰ．はじめに

　20世紀後半，分子生物学，遺伝子工学が革命的な進歩を遂げた．21世紀に入り，2003年4月14日，ヒトゲノムシークエンスの解読完了が宣言され，ポストゲノム時代に入った．マイクロアレイ遺伝子発現プロファイルの解析，一塩基多型 （SNP）探索による疾患関連遺伝子・治療反応性関連遺伝子の同定など，より網羅的な疾患の診断，治療反応性の評価が可能となった．また，ゲノム情報を元にしたゲノム創薬が注目され，多くの分子標的薬剤が開発され，現に癌を中心とした疾患の臨床に使用される時代となった．このような生命科学，基礎医学の顕著な進歩により，脳神経外科学が対象とする疾患にも大きな変化が生じつつある．脳腫瘍の遺伝子異常に関する知識が蓄積され，虚血脳における細胞障害機序が解明され，パーキンソン病などの神経変性疾患の発症機序が解明され，それぞれの疾患の分子遺伝学的なレベルからの理解が進んできたことで，より病因に適した治療法の探索が可能となってきた．

　一方で脳神経外科臨床においても，MRIを代表とした画像診断技術の進歩，マイクロニューロサージャリーの普及，定位脳手術の発展，ガンマナイフを代表とする放射線治療技術の進歩，convection-enhanced delivery（CED）³⁾を代表とする新規投薬技術の開発など，目を見張る進歩がある．このような背景の中で，今後の脳神経外科治療においては，疾患標的治療（disease targeting therapy）が1つの方法論として重要になってくると考えられる．遺伝子レベル，分子レベル，さらには手術治療，放射線治療，化学療法の面からも目的疾患に標的を定めた治療が行われ，疾患治療がより効率的かつ安全なものになる．本稿では，分子レベルでの標的化と薬剤投与段階での標的化をもとにした“疾患標的治療”につき概説する．

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