A scientific breakthrough at Rice University could lead to the first treatment that prevents the build-up of deadly scar tissue in a broad class of diseases that account for an estimated 45 percent of U.S. deaths each year.
"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," said 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, which is called serum amyloid P, or SAP, has proven effective at preventing fibrotic disease from developing in the hearts and lungs of lab animals, and Gomer and colleagues hope it will eventually save thousands of lives once it is developed for human use.
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 FDA-approved treatments to prevent fibrotic tissue from forming, doctors typically consider fibrosis to be an irreversible process, and they try to slow it as much as possible with anti-inflammatory and immunosuppressive drugs.
The biopharmaceutical company Promedior Inc., of Malvern, Pa., 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 of SAP.
Gomer said initial animal tests of SAP at Rice have proven very promising. The tests were conducted on animals that were pre-disposed to developing fibrotic disease in the lungs. The tests found that SAP treatment protected animals from developing dangerous scar tissue.
Gomer said SAP is a naturally occurring protein that 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. Gomer said the tests at Rice show that SAP therapy was successful in preventing fibrotic scarring.
He said SAP research in his lab began in 2001 after a chance meeting between himself and UK immunologist Darrell Pilling. Gomer, who'd spent most of his career studying the single-celled amoebae Dictyostelium, met Pilling at lunch during a cell biology conference. Pilling, who was a post-doctoral research fellow at the University of Birmingham in the UK, had recently identified the factor that promoted lymphocyte survival in the fibrotic joints of rheumatoid arthritis patients. However, 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 proven useful with Dictyostelium. A few days after arriving, the pair noticed a clear interaction between the presence of serum and fibrocytes, and within months 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, but I just couldn't see myself spending the time on it when thousands of people were dying every day from these diseases," Gomer said.
Gomer and Pilling's research is funded by the NIH, and was also funded by the Howard Hughes Medical Institute and the Scleroderma Foundation.
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