Evidences and therapeutic advantages of donanemab in the treatment of early Alzheimer’s disease
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Ajay Kumar Shukla
Abstract
The humanised monoclonal antibody donanemab is being developed to treat early onset Alzheimer’s disease (AD). This drug targets N-truncated pyroglutamate amyloid-peptide at position 3 (N3pG), a modified form of deposited amyloid-peptide. The symptoms of Alzheimer’s disease include gradual memory loss and other cognitive impairments. This disease is characterized by amyloid plaques, which are formed as a result of an accumulation of amyloid-(A-β) peptides. Despite granting donanemab breakthrough therapy designation in June 2021, the FDA rejected donanemab’s accelerated approval application in January 2023, due to inadequate safety data. According to the baseline amyloid level, the time to achieve plaque clearance (amyloid plaque level <24.1 centiloids) varied. Patients with higher baseline levels were more likely to achieve amyloid clearance. The safety of the drug was demonstrated by amyloid-related imaging abnormalities (ARIA), which ranged from 26.1 to 30.5 % in the studies. Clinical trial results have shown that donanemab delays cognitive and functional deterioration in patients with mild to moderate AD. However, it is not yet known whether donenameb offers therapeutic benefits that can change and improve the clinical condition of AD patients. To achieve significant clinical benefits in AD patients with cognitive impairment, further studies may be needed to investigate the interaction between A-β plaque reduction and toxic tau levels.
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Research ethics: Not applicable.
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Informed consent: Not applicable.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. Dr Ajay Kumar Shukla- Idea, review. Dr Saurav Misra- Concept, Writing the article, final editing, Submission.
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Competing interests: All authors state that there is no conflict of interest.
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Research funding: None declared.
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Data availability: Not applicable.
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- Evidences and therapeutic advantages of donanemab in the treatment of early Alzheimer’s disease
- Alzheimer’s disease and clinical trials
- Original Articles
- Pioglitazone attenuate level of myeloperoxidases and nitic oxide in psoriatic lesion: a proof-of-concept study in a imiquimod induced psoriasis model in rat
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- Maternal separation influences hepatic drug-metabolizing CYP450 gene expression without pathological changes in adult mice
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