アルツハイマー病に対する新ワクチン療法―現状とわれわれの試み

Novel Vaccine Therapy for Alzheimer's Disease : Recent Progress and Our Approach

はじめに

　アルツハイマー病は今から100年前，ドイツの精神医学者Alois Alzheimerにより最初に報告された神経疾患である。認知障害（記憶障害，見当識障害，学習の障害，注意の障害，空間認知機能，問題解決能力の障害など）を主症状として中年期以降に多発し，世界中で1,200万人を超える患者が存在すると考えられている^1）。発症後数年の経過を経て徐々に症状は進行し，重度になると摂食や着替え，意思疎通なども不可能となり，数年から十数年で寝たきりになり死に至る。経過中に被害妄想，幻覚や暴言・暴力・徘徊・不潔行為などの問題行動が出現することが多く，患者本人ばかりか家族や介護者を含めて大きな社会問題となっている。

Abstract

　Alzheimer's disease (AD) is the most common cause of dementia with very few drugs available for its treatment.　In 1999, Schenk et al reported that Aβ 1-42 peptide vaccination in AD model mice causes the reduction in Aβ deposits.　Thereafter, a vaccine therapy was developed for the curative treatment of AD.　Clinical trials of active vaccination for AD patients were halted due to the development of meningoencephalitis in some patients; however, vaccine therapy is thought to be effective based on the clinical and pathological findings of the vaccinated patients.　Based on this information, active and passive vaccines have been developed, some of which are now urdergoing clinical trials in Europe and USA.　However, there are still some problems for general application of such drugs for AD patients.　Recently, we developed nonviral DNA vaccines and used them to obtain a substantial Aβ reduction in AD model mice without any side effects.　In this article, we will review conventional vaccine therapies and introduce our non-viral DNA vaccine therapy.　Finally, we will present data regarding the mechanisms of Aβ reduction after DNA vaccination.　DNA vaccination for AD may open up new avenues in vaccine therapy for the treatment of AD.