We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Cynomolgus monkey model of interleukin-31-induced scratching depicts blockade of human interleukin-31 receptor A by a humanized monoclonal antibody.
- Authors
Oyama, Sohei; Kitamura, Hidetomo; Kuramochi, Taichi; Higuchi, Yoshinobu; Matsushita, Hiroaki; Suzuki, Tsukasa; Goto, Masaaki; Adachi, Hideki; Kasutani, Keiko; Sakamoto, Akihisa; Iwayanagi, Yuki; Kaneko, Akihisa; Nanami, Masahiko; Fujii, Etsuko; Esaki, Keiko; Takashima, Yoshiaki; Shimaoka, Shin; Hattori, Kunihiro; Kawabe, Yoshiki
- 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-31 RA) 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-31 RA 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-31 RA 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-31 RA antibody is a promising therapeutic approach for treatment of AD. Nemolizumab is currently under investigation in clinical trials.
- Subjects
KRA; INTERLEUKINS; GROWTH factors; APOPTOTIC bodies; APOPTOSIS; DISEASES
- Publication
Experimental Dermatology, 2018, Vol 27, Issue 1, p14
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/exd.13236