Donanemab is a humanized IgG1 monoclonal antibody. Donanemab targets deposited Aβ42, and clear amyloid plaques in the brain through microglia-mediated phagocytosis. Donanemab mainly localized in the plasma and extracellular space and penetrates the brain across the blood–brain barrier to bind Aβ deposits. Donanemab is an effective treatment for Alzheimer's disease [1-5].
In the platelet-derived growth factor promoter-amyloid precursor protein (PDAPP) mouse model, Aβ42 levels in the hippocampus and cortex of mice were significantly reduced after Donanemab (1.5, 4, and 12.5mg/kg; sc; 6 months) treatment [6].
References:
[1]. Sims JR, Zimmer JA, Evans CD, et al. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. Jama. 2023 Aug 8; 330(6): 512-527.
[2]. Mintun M, Ritchie CW, Solomon P, et al. Donanemab in Early Symptomatic Alzheimer’s Disease: Efficacy and Safety in TRAILBLAZER‐ALZ 2, a Phase 3 Randomized Clinical Trial. Alzheimer's & Dementia. 2023 Dec; 19: e082733.
[3]. Mintun MA, Lo AC, Duggan Evans C, et al. Donanemab in early Alzheimer’s disease. New England Journal of Medicine. 2021 May 6; 384(18): 1691-1704.
[4]. Jayaprakash N, Elumalai K. Translational Medicine in Alzheimer's Disease: The Journey of Donanemab From Discovery to Clinical Application. Chronic Diseases and Translational Medicine. 2024.
[5]. Kang C. Donanemab: first approval. Drugs. 2024 Oct; 84(10): 1313-1318.
[6]. DeMattos RB, Lu J, Tang Y, et al. A plaque-specific antibody clears existing β-amyloid plaques in Alzheimer's disease mice. Neuron. 2012 Dec 6; 76(5): 908-920.