Research press release


Nature Medicine

Medical research: Investigational drugs for prevention of Alzheimer’s disease do not significantly affect cognitive decline



R Batemanたちは、DIADの被験者144人をガンテネルマブ投与群、ソラネズマブ投与群とプラセボ投与対照群のいずれかに割り付けて、7年間観察した。どちらの薬も標的に結合したが、プラセボ群で得られた結果と比較して、AD発症を明らかに遅らせたり、防止したりする効果は見られなかった。しかし、無症状のプラセボ群が認知機能低下を全く示さなかったことを考えると、これらの治療薬の治療効果ははっきりしないままといえる。また、認知機能や臨床症状に対する有効性が観察されなかったことは、有効なAD治療薬開発の妨げになる可能性があるが、ガンテネルマブを投与した患者でADの生物学的特徴の多くが明らかに減少したことは、DIADの初期治療としては有用である可能性を示唆している。


Gantenerumab and solanezumab — investigational drugs for prevention of Alzheimer’s disease — demonstrated no significant impact on cognitive decline in people with dominantly inherited Alzheimer’s disease (DIAD) in a phase 2/3 clinical trial published in Nature Medicine.

DIAD is a rare form of Alzheimer's disease (AD) — estimated to represent less than 1% of cases — in which patients carry genes that predispose them to the disease. Those with DIAD exhibit characteristics that facilitate the investigation of interventions in both the asymptomatic stages of AD and its symptomatic stages, to delay or slow disease progression. These include the development of Alzheimer’s dementia at a predictable age, the presentation of pathological signs of the disease years before symptom onset, and the low likelihood of experiencing other conditions that contribute to cognitive decline.

Randall Bateman and colleagues assigned 144 people with DIAD to treatment with either gantenerumab or solanezumab or a placebo control for up to seven years. Although both drugs engaged their targets, neither was shown to significantly slow or prevent AD compared with results obtained with the placebo. The therapeutic potential of these treatments, however, remain unclear, given that the asymptomatic placebo group showed no cognitive decline. Furthermore, although the observed absence of cognitive or clinical benefit is a potential roadblock in the journey toward the development of effective drugs against AD, significant reductions in many biological features of AD in patients treated with gantenerumab suggest potential utility in the early treatment of DIAD.

The authors conclude that this trial has emphasized the need for improved and more-sensitive cognitive measures in asymptomatic populations, and the use of higher doses over longer timescales to augment drug-target engagement.

doi: 10.1038/s41591-021-01369-8

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