The drug triciribine may stop the progression of two highly fatal respiratory diseases—pulmonary fibrosis and pulmonary hypertension—according to a new study by researchers at the University of Georgia (UGA), in Athens, Ga.
“Our tests show that treatment with triciribine can halt disease progression and may even reverse some of the damage to lung tissue,” said study co-author Somanath Shenoy, PhD, Associate Professor of Clinical and Experimental Therapeutics at UGA’s College of Pharmacy. The researchers recently published their findings in the British Journal of Pharmacology.
Pulmonary fibrosis occurs when lung tissue becomes scarred, leading to loss of lung function and reduced oxygen supply to the blood. It affects nearly 130,000 Americans, and about 48,000 new cases are diagnosed annually, according to the Coalition for Pulmonary Fibrosis.
Pulmonary hypertension involves an increase of blood pressure in the arteries of the lung that can lead to heart failure. Although pulmonary hypertension is rare—only about 15 to 50 cases per million—the total number of deaths attributed to the disease increased by more than 40% in the U.S. between 1980 and 2002, according to the Centers for Disease Control and Prevention.
“The average life expectancy for people with these diseases is only about 5 years after diagnosis, and while the drug treatments we currently have may help improve quality of life, they don’t reduce mortality,” Dr. Shenoy said.
Previous research had already indicated that a protein called Akt1 is at least partly responsible for the development of wound-healing myofibroblasts. Yet, when myofibroblast cells become unregulated, they create scarring, which leads to fibrosis and loss of functional blood vessels in the lungs. To combat this, the researchers developed the drug triciribine to inhibit Akt1.
To test triciribine, the researchers experimented on mice with disease characteristics that mimicked pulmonary hypertension and pulmonary fibrosis in humans. They injected the mice with the drug once daily for a period of 3 weeks. The characteristic scarring and loss of lung vasculature was slowed in every mouse, and the lung tissue of some mice began to return to normal.
“We have also tested this process in human cells taken from diseased lung tissue, and we see very similar results,” Dr. Shenoy said.
The researchers further tested their hypothesis by examining genetically modified mice that do not possess the Akt1 pathway. None of these mice developed disease symptoms, further implicating Akt1 as the primary cause of disease. “To our knowledge, this is the first direct evidence that Akt1 causes disease onset and progression of pulmonary fibrosis and pulmonary hypertension,” he added.
The researchers noted that these results are preliminary, and more trials are needed before they can evaluate triciribine’s efficacy in humans. “We still need to identify the downstream effects of Akt1 inhibition to see if there are any negative side effects,” Dr. Shenoy said. “But if these tests go well, we hope to begin human trials within the next 3 to 5 years.” They anticipate that a human version of triciribine could be administered orally, eliminating the need for daily injections.