Fc-optimized monoclonal antibodies show superior efficacy

Abstract Background Treatment of neuromyelitis optica spectrum disorder (NMOSD) has so far been based on retrospective case series. The results of six randomized clinical trials including five different monoclonal antibodies targeting four molecules and three distinct pathophysiological pathways have recently been published. Methods Literature search on clinical trials and case studies in NMOSD up to July 10. 2020. Results We review mechanism of action, efficacy and side effects, and consequences for reproductive health from traditional immunosuppressants and monoclonal antibodies including rituximab, inebilizumab, eculizumab, tocilizumab and satralizumab. Conclusion In NMOSD patients with antibodies against aquaporin 4, monoclonal antibodies that deplete B cells (rituximab and inebilizumab) or interfere with interleukin 6 signaling (tocilizumab and satralizumab) or complement activation (eculizumab) have superior efficacy compared to placebo. Tocilizumab and rituximab were also superior to azathioprine in head-to-head studies. Rituximab, tocilizumab and to some extent eculizumab have well-known safety profiles for other inflammatory diseases, and rituximab and azathioprine may be safe during pregnancy.

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Ultrastructural analysis of unique glycoconjugates in the rat olfactory system

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100124859 ◽

1992 ◽

Vol 50 (1) ◽

pp. 890-891

Author(s):

James E. Crandall ◽

Linda C. Hassinger ◽

Gerald A. Schwarting

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Monoclonal Antibodies ◽

Olfactory System ◽

Olfactory Bulbs ◽

Temporal And Spatial Patterns ◽

Carbohydrate Epitopes ◽

Olfactory Systems ◽

Temporal And Spatial ◽

Cell Surface Glycoconjugates

Cell surface glycoconjugates are considered to play important roles in cell-cell interactions in the developing central nervous system. We have previously described a group of monoclonal antibodies that recognize defined carbohydrate epitopes and reveal unique temporal and spatial patterns of immunoreactivity in the developing main and accessory olfactory systems in rats. Antibody CC2 reacts with complex α-galactosyl and α-fucosyl glycoproteins and glycolipids. Antibody CC1 reacts with terminal N-acetyl galactosamine residues of globoside-like glycolipids. Antibody 1B2 reacts with β-galactosyl glycolipids and glycoproteins. Our light microscopic data suggest that these antigens may be located on the surfaces of axons of the vomeronasal and olfactory nerves as well as on some of their target neurons in the main and accessory olfactory bulbs.

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Structural and Chemical Studies of Pathological Fibers in Human Neurofibrillary Degeneration

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010012031x ◽

1985 ◽

Vol 43 ◽

pp. 726-729

Author(s):

K.S. Kosik ◽

L.K. Duffy ◽

S. Bakalis ◽

C. Abraham ◽

D.J. Selkoe

Keyword(s):

Monoclonal Antibodies ◽

Alzheimer Disease ◽

Human Brain ◽

Neurofibrillary Tangles ◽

Morphological Analysis ◽

High Specificity ◽

Cytoskeletal Proteins ◽

Neuritic Plaque ◽

Protein Chemistry ◽

Chemical Studies

The major structural lesions of the human brain during aging and in Alzheimer disease (AD) are the neurofibrillary tangles (NFT) and the senile (neuritic) plaque. Although these fibrous alterations have been recognized by light microscopists for almost a century, detailed biochemical and morphological analysis of the lesions has been undertaken only recently. Because the intraneuronal deposits in the NFT and the plaque neurites and the extraneuronal amyloid cores of the plaques have a filamentous ultrastructure, the neuronal cytoskeleton has played a prominent role in most pathogenetic hypotheses.The approach of our laboratory toward elucidating the origin of plaques and tangles in AD has been two-fold: the use of analytical protein chemistry to purify and then characterize the pathological fibers comprising the tangles and plaques, and the use of certain monoclonal antibodies to neuronal cytoskeletal proteins that, despite high specificity, cross-react with NFT and thus implicate epitopes of these proteins as constituents of the tangles.

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