Rice Breakthrough Aims to Prevent Fibrotic Diseases
By Jade Boyd
A scientific breakthrough at Rice University could lead to the first treatment that prevents the buildup of deadly scar tissue in a broad class of diseases that accounts for an estimated 45 percent of U.S. deaths each year.
Fibrosis occurs when the body’s natural healing process goes awry, creating extra scar tissue that does more harm than good. There are dozens of fibrotic diseases, including atherosclerosis, asthma, cirrhosis, scleroderma and pulmonary fibrosis. Since there are no treatments approved by the Food and Drug Administration to prevent fibrotic tissue from forming, doctors typically consider fibrosis to be an irreversible process, and they simply try to slow it as much as possible with anti-inflammatory and immunosuppressive drugs.
“Fibrotic diseases kill so many people because they can crop up in almost any part of the body, and cardiac fibrosis is a particular problem for anyone who’s had a heart attack,” says Richard Gomer, professor of biochemistry and cell biology at Rice. “We’ve discovered a naturally occurring blood protein that prevents dangerous scar tissue from forming.” The protein, called “serum amyloid P,” or SAP, circulates in the bloodstream and plays a crucial role in regulating wound healing. SAP’s role is to inhibit the activity of immune cells called fibrocytes, which make excess collagen that the body uses to heal wounds.
Initial animal tests of SAP at Rice have proved very promising. The first study, done with collaborators at Baylor College of Medicine and published in November in the Proceedings of the National Academies of Science, found that SAP injections prevented the formation of fibrotic scar tissue in the hearts of lab animals. Publication of the first pulmonary fibrosis tests of SAP is expected soon.
Gomer began researching SAP in 2001 after a chance meeting with immunologist Darrell Pilling. Gomer, who’d spent most of his career studying the single-celled amoeba Dictyostelium, met Pilling at lunch during a cell biology conference. Pilling, who was a postdoctoral research fellow at the University of Birmingham in the United Kingdom, had recently identified the factor that promoted lymphocyte survival in the fibrotic joints of rheumatoid arthritis patients. Pilling was hoping to isolate novel biochemical factors associated with high cell-density survival, and Gomer suggested he come to Houston to test some techniques that had proved useful with Dictyostelium. A few days after Pilling’s arrival, the pair noticed a clear interaction between the presence of serum and fibrocytes, and within months they had isolated the active component as SAP.
They immediately recognized the importance of the find. Pilling stayed in Houston as a faculty fellow, and Gomer all but abandoned his internationally recognized work on Dictyostelium. He even quit tinkering with astronomical research gear, a passion he’d nurtured since his days as an undergraduate physics major that allowed him to co-author a number of astrophysical research papers over the years. “Astronomy is a lot of fun,” he says, “but I just couldn’t see myself spending the time on it when thousands of people were dying every day from these diseases.”
Gomer and Pilling’s research has been funded by the National Institutes of Health, the Howard Hughes Medical Institute and the Scleroderma Foundation. The biopharmaceutical company Promedior Inc. has licensed Rice’s SAP technology for use against fibrotic diseases. The company is engaged in animal testing, but has not yet set a date for the first human clinical trials.
