Patients with pulmonary fibrosis and pulmonary hypertension usually don’t survive very long. “The average life expectancy for people with these respiratory diseases is only about five years after diagnosis, and while the drug treatments we currently have may help improve quality of life, they don’t reduce mortality,” said Somanath Shenoy, associate professor at UGA’s College of Pharmacy.
“Our tests showed that triciribine halted disease progression and could even reverse some of the damage to lung tissue.”
Triciribine inactivates a protein called Akt1, which is at least partly responsible for the development of myofibroblasts, cells that migrate to the sites of injury to aid in wound healing. When these cells become unregulated, they create scarring, which leads to fibrosis and loss of functional blood vessels in the lungs.
In their tests, the UGA researchers waited until the mice began to exhibit symptoms of disease and then injected them with triciribine once daily. After three weeks, the characteristic scarring and loss of lung vasculature was slowed in every mouse, and the lung tissue of some of the animals began to return to normal.
Shenoy is quick to point out that these results are preliminary and that more tests are necessary before his team can evaluate triciribine’s efficacy in humans. But the results they already have are still promising. “To our knowledge, this is the first direct evidence that Akt1 causes disease onset and progression of pulmonary fibrosis and pulmonary hypertension,” Shenoy said.
The team is eager to follow up. “We still need to identify the downstream impacts of Akt1 inhibition to see if there are any negative side effects,” said Shenoy. “If these tests go well, we hope to begin human trials within the next three to five years.”
Although no definitive cause for the disease has been identified, pulmonary fibrosis affects nearly 130,000 people in the United States, with about 48,000 new cases diagnosed annually, according to the Coalition for Pulmonary Fibrosis. Pulmonary hypertension is relatively rare—with only about 15 to 50 cases per million people—but the total number of U.S. deaths attributed to the disease increased by more than 40 percent between 1980 and 2002, according to the Centers for Disease Control and Prevention.