Investigations on the expression and relevance of nerve growth factor in dogs with atopic dermatitis

Abstract

Introduction: Human atopic dermatitis (AD) keratinocytes overexpress nerve growth factor (NGF). Its inhibition, or that of its receptor, reduces itch in a mouse model of AD. In this study, we evaluated the expression of NGF in canine AD and assessed the effect of a caninized anti-NGF monoclonal antibody to delay flares of itch in dogs with natural AD. Methods: We used archived frozen skin biopsies from 6 house dust mite–sensitized atopic dogs after allergen challenge, 4 dogs with spontaneous AD and 1 dog with normal skin. The expression of NGF was evaluated by immunofluorescence. We also conducted a pilot crossover trial with 8 dogs with glucocorticoid-responsive AD. In both phases, the dogs were first treated for 28 days with oral prednisolone at 0.5 mg/kg/d. On the first day of the first phase, they received a saline subcutaneous injection, while on that of the second phase, they were injected with 0.2 mg/kg once of the caninized anti-dog NGF ranevetmab. The primary outcome measure was the time-to-flare, defined as the number of days between that of the last prednisolone administration and the day when the pruritus reached a score of at least 5.5/10, or 8 weeks, whichever came first. Results: In normal canine skin, the highest intensity of NGF staining was in stratum granulosum keratinocytes. After allergen challenge and in atopic canine skin, the NGF expression also extended downward to the upper stratum spinosum. In the pilot trial, the time-to-flare after prednisolone cessation was not significantly different between saline and ranevetmab-treated dogs. Discussion: While NGF is overexpressed in the atopic canine epidermis and after allergen challenge in sensitized dogs, the anti-NGF antibody ranevetmab did not delay pruritus flares after the discontinuation of prednisolone. Further studies are needed to assess if NGF is a relevant contributor for canine atopic itch.