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Effect of substituted dextran derivative on complement activation in vivo
H Thomas1, F Maillet, D Letourneur
1INSERM U28, Hôpital Broussais, Paris, France.
Biomaterials
|October 1, 1995
Summary
A novel dextran derivative, CMDBS 25, effectively inhibits complement activation pathways without affecting anticoagulation. This polysaccharide shows promise as a therapeutic agent for complement-mediated diseases.
Area of Science:
- Immunology
- Biochemistry
- Polymer Chemistry
Background:
- The complement system is crucial for innate immunity but its dysregulation contributes to various pathologies.
- Developing safe and effective modulators of complement activation is a key therapeutic goal.
Purpose of the Study:
- To investigate the anticomplementary activity of a novel dextran derivative, CMDBS 25.
- To evaluate its efficacy in vitro and in vivo, and assess its safety profile.
Main Methods:
- Characterization of CMDBS 25, a dextran derivatized with carboxylic and benzylamide sulphonate groups.
- In vitro assessment of complement inhibition in human and rat serum via classical and alternative pathways.
- In vivo studies in Lewis rats involving simultaneous administration with Sephadex G25 to assess systemic complement consumption.
Main Results:
- CMDBS 25 demonstrated significant anticomplementary activity without anticoagulant effects.
- It inhibited both classical and alternative complement pathways in vitro.
- In vivo, CMDBS 25 suppressed Sephadex-induced complement consumption by 98% and showed sustained inhibition with repeated dosing.
- CMDBS 25 was well-tolerated in vivo and did not affect CH50 levels.
Conclusions:
- CMDBS 25 exhibits potent in vitro and in vivo anticomplementary properties.
- The compound effectively modulates complement activation, suggesting its potential as a therapeutic agent for complement-related disorders.