Common drug for allergies and asthma could prevent fibrosis, reduce need for liver transplants

A drug commonly used for the prevention of allergies and asthma someday could find new use in preventing liver disease and reducing the need for transplants, according to new research published in the October 2016 edition of the scientific journal Hepatology.

Led by a team of researchers at Baylor Scott & White Research Institute in conjunction with the Central Texas Veteran's Health Care System and Texas A&M Health Science Center, the study found that cromolyn sodium successfully blocked a series of cells that trigger liver scarring (known as fibrosis), which in advanced cases can lead to cirrhosis. The finding could most impact patients with primary sclerosing cholangitis (PSC), a chronic disease that damages bile ducts and causes serious liver damage. The disease has no effective treatments and leaves patients with few options beyond a liver transplant.

In particular, the study evaluated mast cells (MCs), which are known to infiltrate and multiply after liver injury and release histamine, which causes fibrosis. Using a model that mimics human PSC, researchers found that the drug successfully blocked that histamine, which in turn reduced fibrosis.

"We have been examining mast cells for a number of years in my lab and found that they become more prominent and active during disease, so the overall goal of my research is to find drugs to target mast cells and render them inactive," said Heather L. Bradley-Francis, Ph.D., an investigator at the Digestive Disease Research Center (DDRC) at Baylor Scott & White Health. "This particular study was a direct outgrowth of previous published work involving the same drug for bile duct damage and liver cancer. We were pleasantly surprised to find that our data and results matched what we had hypothesized about the drug's effect on PSC, based on that previous work."

PSC, which causes swelling and scarring in the liver due to short-term damage (such as injury) or long-term damage (such as alcohol abuse), typically is diagnosed in a patient's 30s or 40s. In time, the disease can lead to liver failure, infections or tumors.

"This paper is very important and opens new avenues for the treatment of cholangiopathies," said Gianfranco Alpini, PhD, director of the DDRC at Baylor Scott & White. "Given the limited treatment options for PSC patients, we are thrilled with these study insights."

If more research supports the study's initial findings, investigators see a future where patients could be given the cromolyn sodium drug, which is also used to treat the autoimmune disorder irritable bowel syndrome, for its histamine-blocking properties to prevent the progression of fibrosis. That ultimately could result in fewer liver transplants—and potentially shorter transplant waitlists.

"If you base it off these studies, the possibility of reducing or preventing fibrosis in patients could be very high," Dr. Francis said, adding that, though these results are promising, enthusiasm should be tempered. "We need to perform additional experiments to ensure that we are giving a dose that would be tolerable to humans."

In the meantime, Dr. Francis's team expects to continue with the research.

"We are still very much involved in this work, and I'm optimistic about the future of research and the potential advances that will be made by integrating basic science with clinical research," she said. "My lab has a number of studies that are ongoing right now to identify ways to target mast cells in diseases like PSC, but also in other chronic liver problems like non-alcoholic fatty liver disease. Both of the grants that fund my lab examine the role that mast cells play during different liver pathologies and how mast cells interact with other resident liver cells, so we have a long road ahead to work on better understanding these mechanisms."