Arsenic-based compound reduces lung inflammation in mouse model
Arsenic trioxide is used to treat a type of blood cancer
Arsenic trioxide (ATO) lowered lung inflammation and disease-related alterations to blood vessels in the lungs in a mouse model of scleroderma (SSc), a study reports.
“Our study provides compelling evidence of the positive effects of ATO treatment on lung function in a mouse model of SSc,” researchers wrote in “Arsenic trioxide demonstrates efficacy in a mouse model of preclinical systemic sclerosis,” which was published in Arthritis Research & Therapy. The work was funded by Medsenic, a part of the BioSenic group.
The findings “will provide invaluable knowledge for BioSenic’s ATO application and formulation for the ongoing clinical development, and further contribute towards the future success of ATO’s late-stage clinical development,” François Rieger, PhD, chairman and CEO of BioSenic, said in a company press release.
ATO is an arsenic-based compound for treating a type of blood cancer. It can modulate the activity of different types of immune cells, but its effects aren’t fully understood and vary based on the specific cell type.
Testing ATO in lung inflammation, pulmonary artery pressure
Researchers in France tested ATO in the Fra2TG mouse model, where mice are genetically engineered to develop inflammation and fibrosis (scarring) in their lungs and have increased blood pressure in the pulmonary arteries, which carry blood through the lungs to pick up oxygen, putting strain on the heart.
The pattern of lung and blood vessel changes in the Fra2TG model is similar to what happens in people with SSc-associated pulmonary hypertension, the researchers said. Only female mice were used for the experiments.
Fra2TG mice treated with ATO had significantly lower Ashcroft scores, a measure of lung scarring. They also had significantly lower numbers of several types of inflammatory immune cells (including neutrophils, macrophages, and T-cells) in their lungs. Other markers of fibrosis also tended to be decreased in ATO-treated mice, though they didn’t reach statistical significance.
“The findings from this study showed that ATO treatment reduced interstitial lung damage, as measured by the Ashcroft histological scores. Although some measurements did not reach statistical significance, our results suggest that ATO has a favorable effect on lung inflammation,” the researchers wrote.
ATO treatment also led to a significant decrease in pressure within the pulmonary arteries, as indicated by a 21% decrease in right ventricular systolic pressure, compared to control animals.
The researchers also assessed immune cells to better understand ATO’s biological effects. Treatment with it reduced the activation of T-cells, an immune cell that drives SSc-related inflammation, results suggested.
The findings “support the early use of ATO in SSc patients due to its predominant anti-inflammatory effects and vessel anti-remodeling effects,” said the researchers, who noted more work is needed to investigate the safety and potential utility of ATO in people, given that this was a single study done in a preclinical animal model.
“Compounded observations, both widely published and collected in various international studies, fully justify the initiation of trials on SSc patients … The hope for success is high and BioSenic is working hard in translating the present fundamental results into real therapeutic advances with the necessary help of available international funding,” Rieger said.