Research suggests way to improve stroke treatments

By Dominic Kleinknecht

Eberhard-Karls-University Tübingen

About 800.000 Americans suffer a stroke each year. 87% of which are when blood vessels are blocked by a blood clot which causes hypoxia in the surrounding tissue, known as an ischemic stroke. The standard care of such strokes includes the therapeutic infusion of the trombolytic protein tissue plasminogen activator (tPA), which dissolves the blood clots to restore blood flow. However, it is most effective within the first three hours after the first signs of the stroke, and has another major downside: it can causing swelling in the brain tissue or even bleeding by breaking down the blood-brain-barrier. In an animal study, researchers at Joslin Diabetes Center have recently found that a co-administration of tPA and plasma kallikrein inhibitors could decrease the complications associated with the tPA treatment. tPA normally activates plasma kallikrein, which subsequently activates the kallikrein kinin system. Plasma kallikrein itself promotes blood coagulation, the very cause of strokes in the first place, and the kallikrein kinin system is associated with the previously mentioned brain swelling and breakdown of the blood-brain-barrier. The animal model compared mice with tPA treatment to tPA plus kallikrein inhibitor treatment and found that the additional inhibitor significantly decreased the adverse effects of tPA only treatment. This finding was supported by genetically modified, low kallikrein producing mice under tPA only treatment that also had significantly better results than their unmodified, normal kallikrein producing counterparts under tPA treatment. While a plasma kallikrein inhibitor has already been approved by the FDA for hereditary angioedema, the study has shed new light on the effectiveness of plasma kallikrein inhibitors and underlined the additional potential therapeutic opportunities for such drugs in thrombolytic therapy.

Fabrício Simão, Tuna Ustunkaya, Allen C. Clermont, Edward P. Feener. Plasma kallikrein mediates brain hemorrhage and edema caused by tissue plasminogen activator therapy in mice after stroke. Blood, January 2017 DOI: 10.1182/blood-2016-09-740670