title: Cynomolgus monkey model of interleukin-31-induced scratching depicts blockade of human interleukin-31 receptor A by a humanized monoclonal antibody.
abstract: Scratching is an important factor exacerbating skin lesions through the so-called itch-scratch cycle in atopic dermatitis (AD). In mice, interleukin (IL)-31 and its receptor IL-31 receptor A (IL-31RA) are known to play a critical role in pruritus and the pathogenesis of AD; however, study of their precise roles in primates is hindered by the low sequence homologies between primates and mice and the lack of direct evidence of itch sensation by IL-31 in primates. We showed that administration of cynomolgus IL-31 induces transient scratching behaviour in cynomolgus monkeys and by that were able to establish a monkey model of scratching. We then showed that a single subcutaneous injection of 1 mg/kg nemolizumab, a humanized anti-human IL-31RA monoclonal antibody that also neutralizes cynomolgus IL-31 signalling and shows a good pharmacokinetic profile in cynomolgus monkeys, suppressed the IL-31-induced scratching for about 2 months. These results suggest that the IL-31 axis and IL-31RA axis play as critical a role in the induction of scratching in primates as in mice and that the blockade of IL-31 signalling by an anti-human IL-31RA antibody is a promising therapeutic approach for treatment of AD. Nemolizumab is currently under investigation in clinical trials.
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Sohei
authors.initials: S
authors.lastname: Oyama
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Hidetomo
authors.initials: H
authors.lastname: Kitamura
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Kuramochi
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Higuchi
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsushita
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Goto
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Adachi
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kasutani
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Sakamoto
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Iwayanagi
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Kaneko
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nanami
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Fujii
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Esaki
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Takashima
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Shimaoka
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Hattori
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
authors.forename: Yoshiki
authors.identifier: 0000-0002-6465-7146
authors.initials: Y
authors.lastname: Kawabe
mesh_terms: D000072283:A549 Cells; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D016466:CHO Cells; D002460:Cell Line; D003412:Cricetulus; D018076:DNA, Complementary / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000494:pharmacology*; D007700:Kinetics; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D011537:Pruritus / Q000139:chemically induced* / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000276:immunology / Q000473:pathology; D012871:Skin Diseases / Q000276:immunology / Q000473:pathology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018076:DNA, Complementary; C502187:IL31 protein, human; C502188:IL31RA protein, human; C488159:Il31ra protein, mouse; D007378:Interleukins; D018123:Receptors, Interleukin; C502588:interleukin-31, mouse; C000612881:nemolizumab
keywords: anti-IL-31RA antibody; atopic dermatitis; itch-scratch cycle; nemolizumab; pruritus