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• W2902454313 abstract "Anti-amyloid β (Aβ) immunotherapy represents a major area of drug development for Alzheimer's disease (AD). However, Aβ peptide adopts multiple conformations and the pathological forms to be specifically targeted have not been identified. Aβ immunotherapy-related vasogenic edema has also been severely dose limiting for antibodies with effector functions binding vascular amyloid such as bapineuzumab. These two factors might have contributed to the limited efficacy demonstrated so far in clinical studies.To address these limitations, we have engineered SAR228810, a humanized monoclonal antibody (mAb) with limited Fc effector functions that binds specifically to soluble protofibrillar and fibrillar forms of Aβ peptide and we tested it together with its murine precursor SAR255952 in vitro and in vivo.Unlike gantenerumab and BAN2401, SAR228810 and SAR255952 do not bind to Aβ monomers, low molecular weight Aβ oligomers or, in human brain sections, to Aβ diffuse deposits which are not specific of AD pathology. Both antibodies prevent Aβ42 oligomer neurotoxicity in primary neuronal cultures. In vivo, SAR255952, a mouse aglycosylated IgG1, dose-dependently prevented brain amyloid plaque formation and plaque-related inflammation with a minimal active dose of 3 mg/kg/week by the intraperitoneal route. No increase in plasma Aβ levels was observed with SAR255952 treatment, in line with its lack of affinity for monomeric Aβ. The effects of SAR255952 translated into synaptic functional improvement in ex-vivo hippocampal slices. Brain penetration and decoration of cerebral amyloid plaques was documented in live animals and postmortem. SAR255952 (up to 50 mg/kg/week intravenously) did not increase brain microhemorrhages and/or microscopic changes in meningeal and cerebral arteries in old APPSL mice while 3D6, the murine version of bapineuzumab, did. In immunotolerized mice, the clinical candidate SAR228810 demonstrated the same level of efficacy as the murine SAR255952.Based on the improved efficacy/safety profile in non-clinical models of SAR228810, a first-in-man single and multiple dose administration clinical study has been initiated in AD patients." @default.
• W2902454313 created "2018-12-11" @default.
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• W2902454313 date "2018-11-28" @default.
• W2902454313 modified "2023-10-18" @default.
• W2902454313 title "SAR228810: an antibody for protofibrillar amyloid β peptide designed to reduce the risk of amyloid-related imaging abnormalities (ARIA)" @default.
• W2902454313 cites W1511142149 @default.
• W2902454313 cites W1528113046 @default.
• W2902454313 cites W1567490604 @default.
• W2902454313 cites W1597819025 @default.
• W2902454313 cites W1852570864 @default.
• W2902454313 cites W1927066019 @default.
• W2902454313 cites W1976485053 @default.
• W2902454313 cites W1986154975 @default.
• W2902454313 cites W1989369404 @default.
• W2902454313 cites W1990975951 @default.
• W2902454313 cites W1996024251 @default.
• W2902454313 cites W2004535959 @default.
• W2902454313 cites W2009390338 @default.
• W2902454313 cites W2013148421 @default.
• W2902454313 cites W2016575029 @default.
• W2902454313 cites W2016787780 @default.
• W2902454313 cites W2018744028 @default.
• W2902454313 cites W2023890923 @default.
• W2902454313 cites W2027553957 @default.
• W2902454313 cites W2030325989 @default.
• W2902454313 cites W2050607653 @default.
• W2902454313 cites W2062647232 @default.
• W2902454313 cites W2063236931 @default.
• W2902454313 cites W2067998641 @default.
• W2902454313 cites W2077007913 @default.
• W2902454313 cites W2078992020 @default.
• W2902454313 cites W2080516466 @default.
• W2902454313 cites W2082429191 @default.
• W2902454313 cites W2095212600 @default.
• W2902454313 cites W2100550841 @default.
• W2902454313 cites W2100610042 @default.
• W2902454313 cites W2105758687 @default.
• W2902454313 cites W2108216694 @default.
• W2902454313 cites W2109727228 @default.
• W2902454313 cites W2116386719 @default.
• W2902454313 cites W2133631618 @default.
• W2902454313 cites W2136936410 @default.
• W2902454313 cites W2139976280 @default.
• W2902454313 cites W2140323904 @default.
• W2902454313 cites W2154755614 @default.
• W2902454313 cites W2155932192 @default.
• W2902454313 cites W2160676126 @default.
• W2902454313 cites W2163202463 @default.
• W2902454313 cites W2166976202 @default.
• W2902454313 cites W2168780924 @default.
• W2902454313 cites W2168990989 @default.
• W2902454313 cites W2290076360 @default.
• W2902454313 cites W2373143539 @default.
• W2902454313 cites W2488878741 @default.
• W2902454313 cites W2510806376 @default.
• W2902454313 cites W2524535443 @default.
• W2902454313 cites W2529724290 @default.
• W2902454313 cites W2548126826 @default.
• W2902454313 cites W2554131049 @default.
• W2902454313 cites W2560590017 @default.
• W2902454313 cites W2604285326 @default.
• W2902454313 cites W2728093281 @default.
• W2902454313 cites W2750355784 @default.
• W2902454313 cites W2750472319 @default.
• W2902454313 cites W2766966847 @default.
• W2902454313 cites W2800202520 @default.
• W2902454313 cites W2897855003 @default.
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• W2902454313 doi "https://doi.org/10.1186/s13195-018-0447-y" @default.
• W2902454313 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6264593" @default.
• W2902454313 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30486882" @default.
• W2902454313 hasPublicationYear "2018" @default.
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