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Biotech Begins Clinical Trial for Stroke Treatment

Berislav Zlokovic (University of Southern California)

Berislav Zlokovic (University of Southern California)

ZZ Biotech, a biotechnology company in Houston, began a clinical trial of an experimental drug to treat acute ischemic stroke, where blood flow to the brain is blocked by a clot. The drug being tested is 3K3A-APC, the result of research first conducted at University of Southern California and Scripps Research Institute in California, and developed further by ZZ Biotech.

The drug is an engineered variation of human activated protein C. Research by USC neuroscientist Berislav Zlokovic (pictured right) and Scripps Institute hematologist John Griffin investigated activated protein C because of its ability to stop the growth of blood clots and reduce inflammation; it had already been studied as a treatment for adult sepsis. Their research showed activated protein C decreases cellular signals that tell brain cells to kill themselves after a stroke and boosts the cellular signals that persuade the cells to survive.

Activated protein C, however, has a problem: in its natural state, activated protein C works like a blood thinner, posing a risk of bleeding in the brain. To meet this challenge, Griffin’s hematology lab produced an engineered variation of activated protein C that keeps the desired cell signaling properties, but not the anticoagulation features. That engineered variety became 3K3-APC.

Zlokovic, Griffin, and colleagues tested 3K3-APC with the stroke treatment tissue plasminogen activator (tPA), and against tPA alone, in rodents. The researchers gave tPA with and without 3K3A-APC to test animals about four hours after onset of ischemic stroke. The research team also gave 3K3A-APC for three consecutive days after stroke and measured the amount of brain damage, bleeding, and motor ability of the rodents up to seven days thereafter.

In an article published last month in the journal Stroke, the researchers reported tPA therapy alone caused bleeding in the brains of the test animals. The tPA treatment also did not reduce brain damage or improve motor ability when compared to the control. The combination of tPA and 3K3A-APC, however, reduced brain damage by more than half, eliminated bleeding caused by tPA, and improved the rodents’ motor abilities.

Zlokovic co-founded the parent company of ZZ Biotech in 2000 and serves as ZZ Biotech’s chief scientist, while Griffin serves on the company’s scientific advisory board. ZZ Biotech is developing 3K3A-APC into a treatment and conducting the drug’s clinical trials.

The phase 1 clinical trial now underway is a randomized, double-blind, placebo-controlled study at one site in Austria. Some 62 adult subjects will be assigned sequentially to one of 10 sub-groups, receiving higher single doses, followed by successively higher multiple doses of 3K3A-APC. The company expects to report results of the study in the first quarter of 2013.

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