Washington University Professor of Biochemistry and Molecular Biophysics Enrico Di Cera and a team of researchers at the School of Medicine have engineered and patented a modified enzyme that could safely treat heart attack and stroke victims.
The work of the researchers centers on thrombin, a protein that promotes blood coagulation and blood clots, but also activates protein C, a potent anti-coagulant that has the opposite effect.
Di Cera describes thrombin as “an enzyme with a schizophrenic personality,” capable of distinct and opposing functions depending on the context.
“There’s a delicate balance between coagulation and anti-coagulation,” Di Cera said. “The problem is pushing the equilibrium too far in one direction, which can lead to bleeding. We’re walking a very fine line.”
The researchers have found, however, that WE-thrombin, a rationally engineered variant of thrombin, is devoid of pro-coagulant activity but retains its anti-coagulant function required for thrombolysis.
Di Cera and the team also collaborated with researchers at the Oregon Health and Science University (OHSU).
“We did the structural work and then we joined forces,” Di Cera said.
OHSU began testing WE-thrombin in baboons and discovered that it was more effective and safer than either activated protein C or heparin, which is widely used as an anti-coagulant in clinical practice. Heparin administration also comes with a record of safety issues, including the contamination of stocks produced in China.
“Other anti-coagulants are very good, but don’t have the same safety profile,” Di Cera said.
Di Cera is now submitting a grant application to the National Institutes of Health and getting approval from the Food and Drug Administration for human testing-a process that could take up to two years.
In the meantime, Di Cera is working on removing the affect of thrombin entirely.
“WE-thrombin is excellent, but it’s not the endpoint of the process,” he said. “We’re taking a very comprehensive approach. It’s very rewarding, and we’re very happy. A basic observation 10 years ago in the lab has brought something to fruition.”
Di Cera received his M.D. from the Catholic University in Rome, and in July 1990 came to the University, where he has done continuous research on thrombin and heart disease.