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Taking Donanemab as an Example: A Discussion on the Treatment of Alzheimer’s Disease (AD) with Second-Generation Anti-Aβ Monoclonal Antibodies

Author(s)

Xiaoxuan Kan

Affiliation(s)

School of Pharmacy, University, Lanzhou, Gansu, China

Abstract

Alzheimer’s Disease (AD) is the most common form of dementia in older adults. The high incidence and high rate of disability put a heavy burden on patients' families and society. Abnormal deposition and aggregation of β-amyloid (Aβ) in the brain are the core pathological mechanisms of the onset and the progression of AD, which are also the important target of the current drug development. In the past few years, the second generation anti-Aβ monotoclonal antibodies, represented by, donanumab, have been successively approved for the market release, which is a new direction of the disease-modifying treatment for AD. However, there are still many shortcoming of the existing drugs in the aspect of the eligibility of patient, the longterm eficacy and safety. In this article, we systematically explain the targeted mechanism of action of Donanemab against Aβ, review the preclinical research and the key data of clinical trial of Donanemab in comprehensively, and analyze the limit and the controversy of the practical application of this class of drugs. This review can give a comprehensive reference for the rational clinical application of Donanemab and help to clarify the strength and weakness of the second generation anti-Aβ antibodies. Considering the complicated pathogenesis of AD, the single target intervention is still not enough to get the good therapeutic effect. The future research should focus on the strategy of combination therapy to improve the clinical safety and the longterm benefit of donanliumab.

Keywords

Alzheimer’s Disease; Β-Amyloid; Donanemab; Monoclonal Antibody; Mechanism of Action; Clinical Trial

References

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