Augusta University researchers seek cause of high lung pressure

Grant funds look at protein identified in earlier research
Dr. Scott Barman (left) and Dr. David Fulton have a $2.2 million grant to study a protein that might be involved in causing high blood pressure in the lungs, a serious problem that does not have good treatments and almost always results in death in less than five years after diagnosis. The Augusta research could lead to new drugs.

 

 

Researchers at Augusta University are zeroing in on the potential cause of a devastating lung disease, and a Georgia company could potentially help develop those findings into a new drug.

The research is looking at the causes of pulmonary arterial hypertension, where the blood vessels in the lungs become tougher and narrower and make it more difficult for the heart to pump blood into the lungs, which can eventually lead to heart failure.

There are currently no therapeutics that address the disease, and most patients don’t last five years after diagnosis, the researchers said.

“The drugs will buy time,” said Dr. Da­vid Fulton, the chairman of AU’s Vas­cular Biology Center and a professor of pharmacology and toxicology.

“They are mainly vasodilator drugs that essentially are trying to improve the quality of life, but as far as actual treatment of the disease that really is not therapeutically viable right now,” said Dr. Scott Barman, a professor of pharmacology and toxicology at AU and the vice chairman for education. “The ultimate therapy would be lung transplantation.”

In fact, some of the drugs used to treat the disease are forms of the erectile dysfunction drugs Viagra and Cialis.

“That was a serendipitous finding from some of these patients being treated” for both, Barman said.

The AU researchers have a $2.2 million four-year grant to study a key protein called galectin-3 that might be involved in cells proliferating inside the blood vessels and causing them to stiffen.

In preliminary studies, the AU researchers were able to block that protein and the ensuing overgrowth of cells. That data were presented last month at the American Thoracic Society, Barman said. The AU researchers used an inhibitor of that protein in collaboration with the Norcross-based company Galectin Therapeutics.

“Any pursuit of clinical treatment would be through them,” Fulton said. “Our job is to try to determine the mechanisms.”

The company already has the inhibitor in Phase II clinical trials in other diseases, Barman said. According to the company, it is being tested in clinical trials in non-alcoholic fatty liver disease and in plaque psoriasis. The company could use the AU data to pursue clinical trials in pulmonary hypertension as well if it so chooses, the AU researchers said.

“Our goal is to find out how important it is and to ask the question why,” Fulton said. The question is why it is higher in these patients and why the protein, which is normally in immune cells, is also present in smooth muscle cells that undergo changes in the disease, he said.

Often, these proteins start off as part of a normal inflammatory response that is supposed to end but instead “just goes awry,” Fulton said.

The researchers are also trying to determine whether there might be a related pathway that controls the protein and other processes that might prove to be a better target, he said.

Ultimately, it will be to try and help people with the disease – which affects an estimated 30,000 in the U.S. – get better outcomes, Barman said.

“A lot of patients diagnosed with all of the symptoms and hallmarks of the disease are unfortunately almost past the point (of treatment),” he said.

In March, researchers in Germany and Boston published a study in the journal Heart that found the protein was elevated in patients with the disease compared to people without it and was higher in patients with more advanced stages of the disease. The protein or something present even earlier could provide a better way of identifying those patients sooner, the AU researchers said.

“A goal would be from a diagnostic standpoint to get to these patients earlier so that they would have a fighting chance with properly developed therapeutics,” Barman said.

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Sun, 10/22/2017 - 17:59

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