Rice breakthrough could prevent multiple fibrotic diseases
Tests find protein stops formation of life-threatening scar tissue

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.

The end result of any chronic inflammation of the lung is pulmonary fibrosis. This is a case of chronic bronchitis, and notice the many bands of fibrous scar tissue coursing throughout the lung parenchyma.

Here' a close-up photo of diffuse pulmonary fibrosis. Look closely to see the fine network of fibrous tissue within the parenchyma. I think it is easy to see how this diffuse fibrous growth could decrease lung compliance.

The protein, which is called serum amyloid P, or SAP, has proven effective at preventing fibrotic disease from developing in the hearts 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. Their first study, published in the Proceedings of the National Academies of Science in November with collaborators at Baylor College of Medicine, found that SAP injections prevented the formation of fibrotic scar tissue in the hearts of lab animals. Publication of results on the first pulmonary fibrosis tests of SAP is expected soon, Gomer said.

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 maintaining an elevated level of SAP in the blood is enough to prevent fibrotic diseases from forming.

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.

Source / Credit: Rice University