Research press release





今回、Alfred Sandrockたちは、アミロイドベータタンパク質を選択的に標的とするヒトモノクローナル抗体「アデュカヌマブ」が開発されたことを報告している。Sandrockたちは、トランスジェニックマウスモデルを使った実験で、アデュカヌマブが脳内に入り、可溶性と不溶性のアミロイドベータを用量依存的に減らすことを明らかにした。



同時に掲載されるEric ReimanのNews & Views記事では、「抗アミロイドベータ治療法によって認知機能低下を鈍化させられることが確認されれば、アルツハイマー病の理解と治療法、予防法が大きく変わると考えられる」という結論が示されている。

An antibody therapy that reduces amyloid beta deposits in the brains of patients with mild Alzheimer’s disease is reported in this week’s Nature. The study presents preclinical data and the results of an initial Phase Ib clinical trial, which, together, support the further development of the antibody as an amyloid beta-removing, disease-modifying therapy for Alzheimer’s disease.

Build-up of amyloid beta protein in the brain is a hallmark of Alzheimer’s disease (AD). Amyloid beta-related toxicity is thought to be a primary cause of the synaptic dysfunction and neurodegeneration that underlies the characteristic progression of AD, but attempts to target amyloid beta therapeutically have remained unsuccessful.

Alfred Sandrock and colleagues report the development of aducanumab, a human monoclonal antibody that selectively targets amyloid beta protein. In a transgenic mouse model, the authors show that aducanumab can enter the brain and dose-dependently reduce soluble and insoluble amyloid beta.

The authors also conducted a double-blind, placebo-controlled Phase Ib randomized trial to evaluate the safety and tolerability of monthly aducanumab injections in patients with mild cognitive impairment or mild dementia due to AD and with brain amyloid beta deposits. 165 patients received monthly infusions of either placebo or aducanumab for one year. After 54 weeks of treatment, amyloid beta was significantly reduced in the brains of patients who received aducanumab and higher doses were associated with greater amyloid reduction; there was little change in the brains of those who received the placebo. Of the 40 patients that discontinued treatment, 20 did so due to adverse effects, which included dose-dependent amyloid-related imaging abnormalities.

Higher antibody doses and greater amyloid beta plaque reductions were also associated with slower cognitive decline. However, this study was not designed to definitively address aducanumab’s impact on cognitive decline and the clinical effects of the antibody need to be confirmed in larger studies.

“Confirmation that an anti-amyloid beta treatment slows down cognitive decline would be a game-changer for how we understand, treat and prevent Alzheimer’s disease,” concludes Eric Reiman in an accompanying News & Views article.

doi: 10.1038/nature19323

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