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Development of thrombolytic therapy for stroke: a perspective.
1University of California San Diego, Department of Neuroscience, 9500 Gilman Drive, La Jolla, CA 92093-0624, USA. plapchak@ucsd.edu
Expert Opinion on Investigational Drugs
|November 20, 2002
Summary
New thrombolytic drugs are being developed to improve stroke treatment. These aim to overcome the limitations of current therapies like alteplase (rtPA), focusing on better safety and efficacy for acute stroke management.
Area of Science:
- Neuroscience
- Pharmacology
- Biotechnology
Background:
- Tissue plasminogen activator (alteplase, rtPA) is beneficial for acute stroke but underutilized due to a narrow therapeutic window and bleeding risks.
- Current limitations necessitate the development of novel thrombolytic agents with improved benefit/risk profiles.
Purpose of the Study:
- To review emerging thrombolytic drugs for stroke management.
- To explore new agents that enhance fibrin specificity or prolong half-life.
- To discuss novel plasminogen activators and direct-acting thrombolytics with potential neuroprotective effects.
Main Methods:
- Review of current literature on thrombolytic therapy for stroke.
- Analysis of second-generation alteplase derivatives (tenecteplase, lanoteplase).
- Examination of novel approaches including microplasmin, rDSPA alpha-1, and BB10153.
Main Results:
- Second-generation alteplase derivatives aim to improve fibrin specificity and half-life.
- Microplasmin offers direct thrombolysis and neuroprotection.
- Novel plasminogen activators like rDSPA alpha-1 and BB10153 show promise.
Conclusions:
- Significant advancements are being made in thrombolytic drug discovery for stroke.
- New agents offer potential improvements over existing therapies by addressing safety and efficacy concerns.
- The reviewed drugs represent promising avenues for future acute stroke management.