{"id":189,"date":"2023-05-03T00:48:54","date_gmt":"2023-05-03T00:48:54","guid":{"rendered":"https:\/\/sites.wp.odu.edu\/immunology856\/?p=189"},"modified":"2023-05-03T01:05:40","modified_gmt":"2023-05-03T01:05:40","slug":"mab","status":"publish","type":"post","link":"https:\/\/sites.wp.odu.edu\/immunology856\/2023\/05\/03\/mab\/","title":{"rendered":"-mAb"},"content":{"rendered":"\n

Find me an -mAb: Lecanemab<\/p>\n\n\n\n

Lecanemab, now sold under the brand name Leqembi, is a novel monoclonal antibody recently approved in the US for the treatment of Alzheimer\u2019s disease. Following a Phase III clinical trial published in the January 5th, 2023 The New England Journal of Medicine<\/em>, Biogen Inc.\u2019s new mAb was approved via the FDA\u2019s accelerated pathway for approval of diseases with unmet medical needs (Macmillan, 2023). The targeted disease, Alzheimer\u2019s (AD), is a progressive neurodegenerative disease associated with cognitive decline and memory deficiency (Deture & Dickson, 2019). Though the specific causes of Alzheimer\u2019s are not completely understood, it is known that characteristic changes in the brain result in the loss of neurons and neural connection. According to the FDA (2023), amyloid-beta plaques and neurofibrillary tangles, specifically, result in the loss of neurons and thus the diminished functions of memory and cognition. AD is usually denoted as a sporadic condition, but researchers have identified genetic risk factors associated with onset. According to Deture and Dickson (2019), the disease is thought to be caused by mutations in the presenilin 1 or 2 (PSEN1<\/sub>, PSEN2<\/sub>) genes located on chromosome 21, which are responsible for the production of amyloid precursor protein (APP). As upheld by the National Institute on Aging (2022), such mutation results in the accumulation of amyloid-beta (A\u03b2) plaques, and it is believed that abnormal levels of A\u03b2 clump to form plaque buildup between neurons, resulting in the disruption of cell function. Upon clinical testing, Lecanemab was found to slow clinical decline by 27% after 18 months of treatment through the reduction of A\u03b2 plaque (Macmillan, 2023). The novel drug is an immunoglobulin G, specifically IgG2a<\/sub>.\u00a0<\/p>\n\n\n\n

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Though A\u03b2 can have positive effects in neural tissue, including the prevention of cytotoxic damage and enhancement of plasticity, it can also be toxic, such as in the case of toxic buildup found in Alzheimer\u2019s (Carrillo-Mora et al, 2014). A\u03b2 can disrupt cell signaling in a multitude of ways, including disruption of insulin receptors, MAP kinases, and TLRs, which can lead to lipid and protein peroxidation and mitochondrial dysfunction via the extraction of protons from nearby lipids or proteins. According to Biogen in 2023, Lecanemab, however, \u201cselectively binds to neutralize and eliminate soluble, toxic amyloid-beta (A\u03b2) aggregates that are thought to contribute to the neurodegenerative process in AD\u201d. Formally known as mAb158, Lecanemab works to degrade A\u03b2 protofibrils. The mAb itself is produced by first cleaving IgG at a site below the hinge region, followed by the removal of Fc fragments and non-cleaved antibody from Fab2<\/sub> fragments, which results in IgG2a<\/sub> or RmAb158 (Solivander et al, 2018). Lecanemab then is able to recognize epitopes 1-16 of A\u03b2, as well as 21-29. It is on epitope 22 that the mutation of APP occurs, which results in formation of protofibrils on A\u03b2, and is thought to result in the aggregation of A\u03b2 plaque in cases of Alzheimer\u2019s. mAb158 degrades these protofibrils, which eliminates some of the A\u03b2 plaque via reduction of accumulation, thereby restoring some of the neuronal tissue function and halting some neurodegeneration. <\/p>\n\n\n\n

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References<\/p>\n\n\n\n

Carrillo-Mora, P., Luna, R., & Col\u00edn-Barenque, L. (2014). Amyloid beta: Multiple mechanisms of toxicity and only some protective effects? Oxidative Medicine and Cellular Longevity<\/em>, 2014<\/em>, 1\u201315. https:\/\/doi.org\/10.1155\/2014\/795375<\/p>\n\n\n\n

Commissioner, O. of the. (2023, January 6). FDA grants accelerated approval for alzheimer’s disease treatment<\/em>. U.S. Food and Drug Administration. Retrieved February 5, 2023, from https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-grants-accelerated-approval-alzheimers-disease-treatment<\/p>\n\n\n\n

DeTure, M. A., & Dickson, D. W. (2019). The neuropathological diagnosis of alzheimer\u2019s disease. Molecular Neurodegeneration<\/em>, 14<\/em>(1). https:\/\/doi.org\/10.1186\/s13024-019-0333-5<\/p>\n\n\n\n

LECANEMAB confirmatory phase 3 clarity ad study met primary endpoint, showing highly statistically significant reduction of clinical decline in large global clinical study of 1,795 participants with early alzheimer’s disease<\/em>. Biogen. (2023, January). Retrieved February 5, 2023, from https:\/\/investors.biogen.com\/news-releases\/news-release-details\/lecanemab-confirmatory-phase-3-clarity-ad-study-met-primary<\/p>\n\n\n\n

MacMillan, C. (2023, January 19). Lecanemab, the new alzheimer’s treatment: 3 things to know<\/em>. Yale Medicine. Retrieved February 5, 2023, from https:\/\/www.yalemedicine.org\/news\/lecanemab-leqembi-new-alzheimers-drug<\/p>\n\n\n\n

S\u00f6llvander, S., Nikitidou, E., Gallasch, L., Zy\u015bk, M., S\u00f6derberg, L., Sehlin, D., Lannfelt, L., & Erlandsson, A. (2018). The A\u0392 protofibril selective antibody MAB158 prevents accumulation of A\u0392 in astrocytes and rescues neurons from A\u0392-induced cell death. Journal of Neuroinflammation<\/em>, 15<\/em>(1). https:\/\/doi.org\/10.1186\/s12974-018-1134-4<\/p>\n\n\n\n

U.S. Department of Health and Human Services. (n.d.). What happens to the brain in alzheimer’s disease?<\/em> National Institute on Aging. Retrieved February 5, 2023, from https:\/\/www.nia.nih.gov\/health\/what-happens-brain-alzheimers-disease <\/p>\n","protected":false},"excerpt":{"rendered":"

Find me an -mAb: Lecanemab Lecanemab, now sold under the brand name Leqembi, is a novel monoclonal antibody recently approved in the US for the treatment of Alzheimer\u2019s disease. Following a Phase III clinical trial published in the January 5th, 2023 The New England Journal of Medicine, Biogen Inc.\u2019s new mAb was approved via the […]<\/p>\n","protected":false},"author":21833,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":"","wds_primary_category":0},"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/sites.wp.odu.edu\/immunology856\/wp-json\/wp\/v2\/posts\/189"}],"collection":[{"href":"https:\/\/sites.wp.odu.edu\/immunology856\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.wp.odu.edu\/immunology856\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.wp.odu.edu\/immunology856\/wp-json\/wp\/v2\/users\/21833"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.wp.odu.edu\/immunology856\/wp-json\/wp\/v2\/comments?post=189"}],"version-history":[{"count":4,"href":"https:\/\/sites.wp.odu.edu\/immunology856\/wp-json\/wp\/v2\/posts\/189\/revisions"}],"predecessor-version":[{"id":219,"href":"https:\/\/sites.wp.odu.edu\/immunology856\/wp-json\/wp\/v2\/posts\/189\/revisions\/219"}],"wp:attachment":[{"href":"https:\/\/sites.wp.odu.edu\/immunology856\/wp-json\/wp\/v2\/media?parent=189"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.wp.odu.edu\/immunology856\/wp-json\/wp\/v2\/categories?post=189"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.wp.odu.edu\/immunology856\/wp-json\/wp\/v2\/tags?post=189"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}