Newly Engineered Protein Could Effectively Treat Hemophilia A, Hemophilia B

An enzyme that prevents blood clots from forming and promotes bleeding could be targeted to treat hemophilia, according to a study by researchers at the University of Cambridge and the Children’s Hospital of Philadelphia. The enzyme is called activate protein C (APC).

The approach was developed based on knowledge gathered about another blood disorder called factor V Leiden, in which APC is defective. Those patients experience less-severe bleeding.

“We hypothesized that if we targeted the protein C pathway we could prolong thrombin production,” senior author of the study Prof. James Huntington, of the University of Cambridge, said in a news release.

Thrombin is an essential enzyme for the formation of blood clots. Defects in APC result in overproduction of thrombin and leads to factor V Leiden, which is characterized by excessive clotting and thrombosis.

For the study “Design and characterization of an APC-specific serpin for the treatment of haemophilia,” published in the American Society of Hematology’s journal Blood, the researchers developed a direct inhibitor of APC by modifying an enzyme called serpin, which can selectively prevent APC from turning off thrombin production.

Researchers administered the engineered serpin to mice with hemophilia B. When they clipped the tails of the animals to promote bleeding, they saw that bleeding decreased as the dose of the serpin increased. Levels observed in healthy mice were reached at the highest dose.

The researchers then assessed whether the engineered serpin was also able to promote clotting in humans. When they added the serpin to blood samples obtained from hemophilia A patients, they saw that serpin was able to accelerate blood clot formation. The researchers concluded that the engineered serpin could be used to treat hemophilia patients.

“Because we are targeting a general anti-clotting process, our serpin could effectively treat patients with either hemophilia A or B, including those who develop inhibitors to more traditional therapy,” Huntington said in the news release.

He also added that because the serpin can be subcutaneously delivered and is long-acting, patients would no longer need to endure the cumbersome thrice-weekly infusions that are currently used in therapeutic regimens.

Study co-author Dr. Trevor Baglin, MD, of the Addenbrooke’s Hospital in Cambridge, said the team hopes to test the serpin in human clinical trials within the next three years.

“It is important to remember that the majority of people in the world with hemophilia have no access to therapy. A stable, subcutaneous, long-acting, effective hemostatic agent could bring treatment to a great deal many more hemophilia sufferers,” Baglin said.