S Murthy1, A Flanigan, D Coppola, R Buelow. 1. Division of Gastroenterology and Hepatology, Drexel University College of Medicine, 245 N 15th Street, Philadelphia, PA 19102-1192, USA, s.Murthy@drexel.edu
Abstract
OBJECTIVE AND DESIGN: RDP58 is a novel anti-inflammatory peptide that inhibits TNF synthesis and upregulates heme oxygenase-1. RDP58 therapy was evaluated in the dextran sodium sulphate (DSS) model of chronic colitis. MATERIAL: Colitis was induced by giving DSS to mice (n = 8 animals/group). Toxicity studies were done in Rhesus monkeys (n = 5), dogs (n = 3) and mice (n = 10). TREATMENT: In colitis, mice were treated with p.o. vehicle (saline), RDP58 (5 and 10 mg/kg/day) or 5-ASA (50 mg/kg/day). METHODS: Disease activity index (DAI) was used as the endpoint of efficacy. RESULTS: RDP58 therapy significantly reduced DAI and histological scores in all animals. DAI scores in RDP58 treated animals declined faster than 5-ASA. RDP58 at 5 or 10 mg/ kg/day significantly reduced DAI compared to 5-ASA. RDP58 significantly reduced acute, chronic and total inflammation scores. It enhanced re-epithelialization by reducing crypt scores. RDP58 was not bioavailable and was well tolerated. CONCLUSIONS: Therapeutic efficacy of RDP58 combined with a lack of bioavailibility and toxicity suggest that RDP58 may be a promising new therapeutic for IBD.
OBJECTIVE AND DESIGN: RDP58 is a novel anti-inflammatory peptide that inhibits TNF synthesis and upregulates heme oxygenase-1. RDP58 therapy was evaluated in the dextran sodium sulphate (DSS) model of chronic colitis. MATERIAL: Colitis was induced by giving DSS to mice (n = 8 animals/group). Toxicity studies were done in Rhesus monkeys (n = 5), dogs (n = 3) and mice (n = 10). TREATMENT: In colitis, mice were treated with p.o. vehicle (saline), RDP58 (5 and 10 mg/kg/day) or 5-ASA (50 mg/kg/day). METHODS: Disease activity index (DAI) was used as the endpoint of efficacy. RESULTS: RDP58 therapy significantly reduced DAI and histological scores in all animals. DAI scores in RDP58 treated animals declined faster than 5-ASA. RDP58 at 5 or 10 mg/ kg/day significantly reduced DAI compared to 5-ASA. RDP58 significantly reduced acute, chronic and total inflammation scores. It enhanced re-epithelialization by reducing crypt scores. RDP58 was not bioavailable and was well tolerated. CONCLUSIONS: Therapeutic efficacy of RDP58 combined with a lack of bioavailibility and toxicity suggest that RDP58 may be a promising new therapeutic for IBD.
Authors: Xiangli Cui; Yu Jin; Anne B Hofseth; Edsel Pena; Joshua Habiger; Alexander Chumanevich; Deepak Poudyal; Mitzi Nagarkatti; Prakash S Nagarkatti; Udai P Singh; Lorne J Hofseth Journal: Cancer Prev Res (Phila) Date: 2010-03-23
Authors: Lucía Márquez; Beatriz G Pérez-Nievas; Icíar Gárate; Borja García-Bueno; José Lm Madrigal; Luis Menchén; Gabino Garrido; Juan C Leza Journal: World J Gastroenterol Date: 2010-10-21 Impact factor: 5.742