Triciribine Drug Able to Halt Progression of Pulmonary Fibrosis and Pulmonary Hypertension in Mice

Researchers at the University of Georgia and the Georgia Regents University discovered that the drug triciribine can halt the progression of fatal respiratory diseases like pulmonary fibrosis and pulmonary hypertension. The study was recently published in the British Journal of Pharmacology and is entitled “Akt inhibitor, triciribine, ameliorates chronic hypoxia-induced vascular pruning and TGFβ-induced pulmonary fibrosis.”

Pulmonary fibrosis is a progressive fatal lung disease in which the alveoli and the lung tissue are damaged, becoming thick and scarred (fibrosis), leading to severe breathing difficulties and compromising oxygen transfer between the lungs and the bloodstream. The disorder is characterized by a shortness of breath that gradually worsens, with respiratory failure being the main cause of death associated with it. There is no cure and it is estimated that almost 130,000 individuals in the United States suffer from pulmonary fibrosis. The disease has a poor prognosis and around two-thirds of the patients die within five years after being diagnosed.

Pulmonary hypertension is a life-threatening condition characterized by the increase of blood pressure in the pulmonary arteries that supply blood to the lungs, leading to inflammation, increased pulmonary vascular resistance and gradual occlusion of pulmonary vessels. Pulmonary hypertension can cause difficulties in breathing, right-sided heart failure and eventually death. Overall, patients with this disorder have a poor prognosis. Pulmonary hypertension is estimated to affect 15 to 50 individuals per million people.

“The average life expectancy for people with these 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,” noted the study’s senior author Dr. Somanath Shenoy in a news release. “Our tests show that treatment with triciribine can halt disease progression and may even reverse some of the damage to lung tissue.”

Triciribine inhibits the production of a protein called Akt1, which is involved in the development of myofibroblasts, cells that migrate to the injured sites and help in the wound healing process. The deregulation of myofibroblasts leads to tissue scarring, fibrosis and the loss of functional blood vessels in the lungs.

In the study, the team tested the therapeutic benefit of triciribine using mouse models of pulmonary hypertension and pulmonary fibrosis. When mice exhibited symptoms of the disease, they were injected once daily with triciribine for a period of three weeks.

Researchers found that the typical scarring and loss of lung vasculature was slowed in the mice tested and that, remarkably, the lung tissue of some of the animals began to return to normal. Using genetically modified mice without the Akt1 pathway, researchers found that none of the animals developed disease symptoms, further indicating that Akt1 is the primary cause of the disease.

“To our knowledge, this is the first direct evidence that Akt1 causes disease onset and progression of pulmonary fibrosis and pulmonary hypertension,” emphasized Dr. Shenoy. “We have also tested this process in human cells taken from diseased lung tissue, and we see very similar results.”

The team emphasizes, however, that these are preliminary results and that more tests need to be performed before triciribine’s efficacy can be evaluated in humans. In this case, triciribine could be formulated as an oral drug avoiding the need for daily injections.

“We still need to identify the downstream effects of Akt1 inhibition to see if there are any negative side effects,” concluded Dr. Shenoy. “But if these tests go well, we hope to begin human trials within the next three to five years.”