When Dr. Charles Esmon began studying activated protein C in the 1970s, he never imagined his work would lead to a pair of life-saving drugs.
“Back then, we didn’t even know what activated protein C did in the body,” said the Oklahoma Medical Research Foundation scientist. “Our goal was to figure it out.”
Figure it out he did. Indeed, Esmon’s research on the naturally occurring protein helped create two FDA-approved drugs: one (Baxter’s Ceprotin) for children suffering from life-threatening protein C deficiencies, another (Eli Lilly’s Xigris) for severe sepsis, a blood infection that kills more than 200,000 Americans each year.
And now OMRF’s Esmon, working with collaborators around the globe, is exploring a host of new disease applications for activated protein C. In their crosshairs is a staggering array of illnesses, from diabetes to multiple sclerosis to heart attacks and stroke.
At the University of Rochester, physicians are beginning a human clinical trial to study the viability of treating stroke patients with activated protein C. And at institutions in the U.S. (Stanford University, the University of California and San Francisco and Louisiana State University) and abroad (universities in Italy and Germany), scientists are using animal models of diabetes, multiple sclerosis, Crohn’s disease, heart failure, asthma and lung injury to explore the protein’s efficacy in treating those conditions.
“What we found with sepsis is that activated protein C was protective in situations where you had inflammation, vascular injury and organ damage as part of the disease process,” said Esmon, who holds the Lloyd Noble Chair in Cardiovascular Research at OMRF. “So now we’re looking at other illnesses, conditions where blocking inflammatory response and coagulation and protecting organs could be beneficial.”
Promising results for the prevention of kidney damage in mouse models in diabetes were published in the journal Nature Medicine. And in the February 28 issue of Nature, a team led by Stanford University researchers showed that activated protein C was an effective treatment for a mouse version of multiple sclerosis.
Esmon stressed that such studies, while promising, were a long way from the clinic. “The next step would be more animal studies. If those were effective, then you’d try to convince a drug company to take on the project and commence drug trials. That’s a process that takes a decade and costs hundreds of millions of dollars.”
Still, that process has progressed significantly for the treatment of stroke. “It’s been ten years since we first suggested using activated protein C as a therapeutic for patients who have suffered strokes,” said Esmon. “So it’s exciting to see human clinical trials begin.”
Esmon hopes that his work will bring relief to as many disease sufferers as possible. “That first patient”—an infant suffering from protein C deficiency—“who was treated with activated protein C and recovered was an amazing thrill.” He still keeps a photo of the child outside of his office at OMRF. “If activated protein C has broader implications to a wider variety of patients, that would be wonderful.”
Long recognized as a world leader in the study of cardiovascular disease, Esmon is a member of the National Academy of Sciences and Oklahoma’s only Howard Hughes Medical Institute investigator. He joined OMRF’s scientific staff in 1982.
OMRF is an independent, nonprofit biomedical research institute dedicated to understanding and developing more effective treatments for human disease. Chartered in 1946, its scientists focus on such critical research areas as Alzheimer’s disease, cancer, lupus and cardiovascular disease.