Treatment of collagen induced arthritis in DBA/1 mice with L-asparaginase
1Division of Rheumatology, Childrens Hospital Los Angeles, California 90027, USA. reiff@hsc.usc.edu
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.
Insights
L-asparaginase effectively reduced arthritis severity in mice, showing potent antiarthritic properties. This study suggests L-asparaginase as a promising treatment for rheumatoid arthritis.
Area of Science:
- Immunology
- Rheumatology
- Pharmacology
Background:
- Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation.
- Current treatments for RA can have significant side effects and varying efficacy.
- Novel immunosuppressive agents are needed for effective RA management.
Purpose of the Study:
- To investigate the efficacy and safety of L-asparaginase as an immunosuppressive therapy.
- To evaluate its potential in a collagen-induced arthritis (CIA) mouse model.
- To assess both preventative and therapeutic effects on arthritis development and progression.
Main Methods:
- Male DBA/1 mice were induced with collagen-induced arthritis (CIA).
- Mice received varying doses of native or pegylated L-asparaginase (PEG-L-asparaginase) via intraperitoneal injection.
- Arthritis severity was scored over 4 weeks, with X-rays used for joint evaluation.
Main Results:
- Both native and PEG-L-asparaginase significantly reduced mean arthritic scores in established CIA (p < 0.001 for PEG-L-asparaginase).
- Pre-emptive administration of native L-asparaginase significantly decreased arthritis incidence, paw involvement, and severity (p < 0.0001).
- X-ray analysis revealed significant differences between treated and control groups, with no drug-related toxicity observed.
Conclusions:
- L-asparaginase demonstrates potent antiarthritic activity in a CIA mouse model.
- The findings suggest L-asparaginase as a potential second-line treatment for rheumatoid arthritis.
- Further studies in juvenile and adult RA patients are warranted.
