BRAIN and NERVE－神経研究の進歩69巻8号

2017年08月発行

特集 遺伝性脊髄小脳失調症の病態と治療展望

HMGB1補充による脊髄小脳失調症1型に対する分子標的治療

著者： 藤田慶大¹ 岡澤均¹

所属機関： ¹東京医科歯科大学難治疾患研究所神経病理学分野

ページ範囲：P.925 - P.932

文献概要

脊髄小脳失調症1型（SCA1）は依然として根本的治療の存在しない神経変性疾患の1つである。私たちは網羅的プロテオーム解析からSCA1病態において小脳神経細胞核内でHMGB1が減少していることを発見した。DNA構造蛋白質であるHMGB1の核内減少は，DNA損傷修復と転写という2つの主要な核機能の低下，また神経変性につながるものと考えられる。私たちはアデノ随伴ウイルスベクターを用いたHMGB1による遺伝子治療を開発し，モデルマウスにおけるproof of concept（POC）を得て，ヒト臨床試験の準備を開始している。

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