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DISEASE APPEARS IN MANY AREAS
Fibrosis occurs when the body's natural healing process goes awry. There are dozens of fibrotic diseases, including:
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.
Gary Fountain: For the Chronicle
ion>Rice researchers Darrell Piling, left, and Richard Gomer review an analysis of purified SAP protein. They hope the protein will one day fight fibrotic diseases.
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A chance meeting in a crowded cafeteria led to a scientific discovery that someday could help millions of people with fibrotic diseases.
The two scientists who met over lunch later discovered a blood protein that prevents unnecessary scar tissue from forming in organs affected by disease or injury.
Beneficial scar tissue pulls together and fills in wounds, explains Richard Gomer, a professor of biochemistry and cell biology at Rice University. "The problem is there are lots of things in humans that can accidentally trigger this wound-healing process."
Excess scar tissue sometimes forms where it isn't needed. This can lead to fibrotic diseases including asthma, cirrhosis, scleroderma, pulmonary fibrosis and hardening of the arteries. Scar tissue in the heart can cause arrhythmias and congestive heart failure.
"From what we've read, at least 1,000 people a day are dying from these different fibrosing diseases," Gomer says.
An invitation to Rice
Neither Gomer nor his research partner, Rice fellow Darrell Pilling, was studying fibrosis when they met six years ago at a cell-biology conference in England.
Pilling, then the sleep-deprived father of a 2-week-old daughter, had hoped to avoid conversation when he sat down at a lunch table alone. Seeing no familiar faces in the cafeteria, Gomer introduced himself to the young scientist.
Pilling had been having trouble purifying proteins that affect white blood cells in rheumatoid arthritis patients. Gomer invited him to Rice, where he had been identifying proteins secreted by Dictyostelium, a single-celled amoeba.
In the first week of what was to be a yearlong fellowship for Pilling, the two researchers set up an experiment with two groups of white blood cells. They placed one group in blood serum and another in a culture without it.
Certain white blood cells in the second group quickly became fibrocytes, long, skinny cells that form scar tissue. Fibrocytes did not materialize in the culture containing the liquid part of blood.
"It didn't take many neurons to work out that there was something in the serum that was keeping them from differentiating," Pilling recalls.
Further work purifying blood proteins identified serum amyloid P, or SAP, as the agent that prevents fibrotic tissue from forming.
Asthmatics may benefit
As Gomer and Pilling continue experimenting with cultures and lab mice, Rice's SAP technology has been licensed to a Pennsylvania-based startup company, Promedior Inc., to develop clinical applications. Their research has been funded by the National Institutes of Health, the Howard Hughes Medical Institute and the Scleroderma Foundation.
One group of patients who could benefit from further research are asthmatics such as Brenda Fielden, a 56-year-old cell-phone sales representative from southeast Houston. Fielden has always had respiratory problems and was diagnosed with asthma 16 years ago.
"It gets to the point that it hurts so bad that I would unconsciously hold my breath," Fielden says.
Newer medications make a huge difference for Fielden, although she said this cold, wet winter has taken its toll. One physician estimated her lung capacity at 65 percent a few years ago.
"If asthma is severe and long-term, it can cause fibrosis, and this contributes to loss of lung function," explains Michael Blackburn, a professor of biochemistry and molecular biology at the University Texas Medical School at Houston.
"What Dr. Gomer is showing is that SAP is very important for regulating the presence of fibroblasts in the lungs," says Blackburn, who also is studying pulmonary fibrosis.
He is searching for a chemical to block adenosine receptors. Adenosine also has been implicated in the formation of fibrotic lung tissue.
Elsewhere in Houston, physicians say potential SAP-related treatments could help patients with cardiac fibrosis that can lead to congestive heart failure.
"Fibrosis in the heart is the leading cause of chronic cardiac illness in the world," says Dr. Mark Entman, scientific director of the DeBakey Heart Center at The Methodist Hospital and Baylor College of Medicine. "Fibrosis frequently turns people into cardiac cripples."
Entman, Pilling and several other researchers worked together on a study published late last year that showed SAP prevented fibrosis in lab mice that should have been prone to it.
Further research by Entman's team identified a cellular receptor with which SAP interacts to prevent white blood cells from forming fibrosis. He thinks developing a pharmaceutical product that targets this receptor might be more efficient than treating patients with SAP itself.
"It's hard to give a protein all the time," Entman says. "To give infusions of a protein several times a week would be very expensive."
Years of work ahead
Years of research remain before human patients might benefit from these Houston breakthroughs.
Scientists and physicians must determine whether SAP acts the same way in humans as it does in mice and whether it can prevent fibrosis in other parts of the body.
Meanwhile, Gomer has all but abandoned his internationally recognized work with Dictyostelium and set aside a keen interest in astrophysics.
"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.
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