OBJECTIVE: To evaluate the safety and efficacy of L-asparaginase as an immunosuppressive agent in a mouse model of rheumatoid arthritis. METHODS: Male DBA/1 mice with collagen-induced arthritis (CIA) were treated at different intervals with various doses of native and pegylated L-asparaginase from E. coli. The mice were observed for 4 weeks during which time arthritis was scored. Outcome parameters included effect on severity and progression of established arthritis as well as prevention of disease. In addition, X-rays from the affected joints were obtained for comparison. RESULTS: Both native L-asparaginase at a dose of 50 IU/injection intraperitoneally three days a week and pegylated asparaginase (PEG-L-asparaginase) at a dose of 25 IU/injection twice a week, significantly reduced the mean arthritic score (MAS) in mice with established arthritis (p < 0.001 for PEG-L-asparaginase). When native L-asparaginase was administered before the onset of arthritis (days 14-post immunization) the number of mice developing arthritis as well as the number of arthritic paws and the severity of arthritis in the treatment group were significantly decreased (p < 0.0001). Significant differences were found in the X-ray evaluation between treated and control mice. None of the animals died due to drug related events or showed signs of asparaginase induced toxicity. CONCLUSION: Our data provide the first direct evidence that L-asparaginase is a potent antiarthritic agent and may represent an effective second line agent for future treatment studies in juvenile and adult rheumatoid arthritis.
OBJECTIVE: To evaluate the safety and efficacy of L-asparaginase as an immunosuppressive agent in a mouse model of rheumatoid arthritis. METHODS: Male DBA/1 mice with collagen-induced arthritis (CIA) were treated at different intervals with various doses of native and pegylated L-asparaginase from E. coli. The mice were observed for 4 weeks during which time arthritis was scored. Outcome parameters included effect on severity and progression of established arthritis as well as prevention of disease. In addition, X-rays from the affected joints were obtained for comparison. RESULTS: Both native L-asparaginase at a dose of 50 IU/injection intraperitoneally three days a week and pegylated asparaginase (PEG-L-asparaginase) at a dose of 25 IU/injection twice a week, significantly reduced the mean arthritic score (MAS) in mice with established arthritis (p < 0.001 for PEG-L-asparaginase). When native L-asparaginase was administered before the onset of arthritis (days 14-post immunization) the number of mice developing arthritis as well as the number of arthritic paws and the severity of arthritis in the treatment group were significantly decreased (p < 0.0001). Significant differences were found in the X-ray evaluation between treated and control mice. None of the animals died due to drug related events or showed signs of asparaginase induced toxicity. CONCLUSION: Our data provide the first direct evidence that L-asparaginase is a potent antiarthritic agent and may represent an effective second line agent for future treatment studies in juvenile and adult rheumatoid arthritis.
Authors: Hamza Rafeeq; Asim Hussain; Muhammad Haseeb Anwar Tarar; Nadia Afsheen; Muhammad Bilal; Hafiz M N Iqbal Journal: 3 Biotech Date: 2021-10-01 Impact factor: 2.893
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Authors: Hien Anh Nguyen; Ying Su; Jenny Y Zhang; Aleksandar Antanasijevic; Michael Caffrey; Amanda M Schalk; Li Liu; Damiano Rondelli; Annie Oh; Dolores L Mahmud; Maarten C Bosland; Andre Kajdacsy-Balla; Sofie Peirs; Tim Lammens; Veerle Mondelaers; Barbara De Moerloose; Steven Goossens; Michael J Schlicht; Kasim K Kabirov; Alexander V Lyubimov; Bradley J Merrill; Yogen Saunthararajah; Pieter Van Vlierberghe; Arnon Lavie Journal: Cancer Res Date: 2018-01-17 Impact factor: 12.701