Office of Technology Transfer – University of Michigan

Methods of Reducing Vascular Permeabiity in Tissue by Inhibition of Tissue Plasminogen Activator (tPA) and tPA Inhibitors Useful Therein

Technology #3277

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Researchers
Daniel A. Lawrence
Managed By
Tiefei Dong
Senior Licensing Specialist, Life Sciences 734-763-5332
Patent Protection
US Patent 7,375,076

Methods of reducing vascular permeability in tissue by inhibition of tissue plasminogen activator (tPA)

Cerebral edema, excess accumulation of fluid in spaces of the brain, is one of the most common pathophysiological conditions and is associated with other serious disorders and conditions such as ischemic stroke, brain tumor, and diabetes. Considering approximately 1 out of every 19 deaths in the US is due to stroke and brain tumors and 9.3% of the US population lives with diabetes, there is a large proportion of patients regularly suffering from pathological cerebral edema. One of the mechanisms leading to cerebral edema is the increase of tPA, which increase leakiness of blood-brain-barrier. A patented technology inhibits tPA activity to effectively control permeability of blood vessels providing attractive therapeutic options for many patients who are dealing with complications from stroke, cancer, and diabetes.

tPA inhibition without disrupting tPA’s role as an anti-blood clot

The invention indirectly reduces vascular permeability by interfering with tPA’s interaction with low density lipoprotein receptor-related protein which is required for tPA’s role in modulating permeability of blood-brain-barrier. This allows tPA to function normally as a anti-blood clot agent, yet preventing tPA to cause cerebra edema. The effectiveness of this novel tPA inhibitor has been tested in a mouse model in vivo.

Advantages

  • The activity of tPA inhibited by the invention is independent of tPA’s native activity as a anti-blood clotting agent.
  • The novel tPA inhibitors can be administered in many ways such as intravenously, intrathecally, or via nasal spray

Applications

  • Reduction of blood-brain-barrier permeability
  • A companion treatment of tPA administration to prevent side-effects that are related to excessive permeabilization of blood vessels.