Galectin Therapeutics, Inc. recently reported that GR-MD-02, the company’s lead candidate galectin-3 (gal-3) inhibitor, has demonstrated a positive effect on vascular remodeling in mouse models of pulmonary arterial hypertension (PAH).
The data was recently presented by a team of researchers from the Vascular Biology Center and the Department of Pharmacology and Toxicology at Augusta University during the American Thoracic Society (ATS) 2016 International Conference.
Pulmonary hypertension (PH) is high blood pressure in the main arteries that supply blood to the lungs which is caused by the narrowing and constriction of blood vessels in the lungs themselves. The elevated blood pressure increases the work required of the heart’s right ventricle to pump blood into the lung, which eventually culminates in failure of the right ventricle, circulatory collapse, and death.
The primary cause of the permanently elevated pulmonary vascular resistance in PAH occurs because of obstruction in vascular remodeling. Treatments with vasodilators can help with the symptoms so that PAH patients can live a better quality of life, but the therapies need to address the structural narrowing of pulmonary arteries.
The data presented during the ATS meeting showed that PAH mice models have increased right ventricular wall thickness, right ventricular hypertrophy, increased right ventricular systolic pressure, fibrosis and pulmonary arterial smooth muscle proliferation, and lower pulmonary blood flow.
Additionally, in mice models and in humans with the disease, researchers found an induction of gal-3 expression in the smooth muscle layer. When the researchers treated the mice with the gal-3 inhibitors GR-MD-02 and GM-CT-01, they observed an improvement in heart features as well as in vascular remodeling related with PAH.
The results from the animal studies suggest that anti-galectin therapies, and specifically GR-MD-02, might provide a new therapeutic approach for seriously ill patients.
Currently, approved therapies that help dilate constricted pulmonary arteries exist, but there are no therapies that effectively change the structure of the arteries or reverse the long-term course of the disease. A drug that can reverse the arterial smooth muscle and fibrosis findings in PAH might play an important role in treating these patients.
“The alterations in cardiopulmonary function and vascular proliferation, as well as in fibrosis were significantly attenuated by in vivo treatment with specific gal-3 inhibitors,” said David Fulton, director of the Vascular Biology Center at Augusta University, according to a news release. “These findings indicate that gal-3 signaling contributes to the compromised pulmonary vascular function and prominent pulmonary arterial remodeling that occurs in PAH, which suggests that inhibition of gal-3 is a strategic and viable target for treatment of PAH and other related pulmonary vascular diseases.”
Dr. Peter G. Traber, chief executive officer and chief medical officer of Galectin Therapeutics and an author of the study, said the “intriguing results” of the study suggest another important indication for therapy with gal-3 inhibitors.
“The severity of PAH is such that over half of patients die of the disease within seven years of initial diagnosis. A new therapeutic approach that addresses vascular remodeling would be a welcome addition to the vasoactive drugs currently on the market,” Traber said.