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Thrombolytic activity of BB-10153, a thrombin-activatable plasminogen
M B Comer1, K S Cackett, S Gladwell
1British Biotech, Oxford, UK.
Journal of Thrombosis and Haemostasis : JTH
|January 7, 2005
Summary
BB-10153, a novel thrombolytic agent, demonstrated effective clot lysis in vivo with reduced reocclusion and bleeding compared to t-PA. Its long half-life and thrombus-selective activation offer potential advantages over current treatments.
Area of Science:
- Biochemistry
- Pharmacology
- Cardiovascular Research
Background:
- BB-10153 is an engineered human plasminogen variant.
- Designed for thrombin-activated conversion to plasmin at thrombi.
- Aims to act as a targeted thrombolytic prodrug.
Purpose of the Study:
- Evaluate in vivo thrombolytic properties of BB-10153.
- Compare BB-10153 efficacy and safety with tissue-type plasminogen activator (t-PA).
- Assess performance without co-administered heparin.
Main Methods:
- Utilized a femoral artery copper coil thrombosis model in dogs and rabbits.
- Administered BB-10153 intravenously (5 mg/kg in dogs, 10 mg/kg in rabbits).
- Compared reperfusion rates, reocclusion, bleeding times, and plasma alpha2-antiplasmin levels against t-PA.
Main Results:
- BB-10153 achieved comparable reperfusion to t-PA.
- Significantly reduced reocclusion rates versus t-PA (2/6 dogs, 0/10 rabbits vs. 4/4 dogs, 5/7 rabbits).
- Did not affect bleeding time or alpha2-antiplasmin; t-PA increased bleeding time and depleted these markers. BB-10153 plasma half-life was 3-4 hours.
Conclusions:
- BB-10153 exhibits thrombus-selective thrombolytic activity.
- Its long half-life and targeted activation may mitigate bleeding and reocclusion issues.
- BB-10153 shows promise as an improved thrombolytic agent.