Multiple Sclerosis Treatment, Tecfidera, Seen to Ease Fibrosis and Inflammation in Early PAH Study
The approved multiple-sclerosis treatment Tecfidera was seen to improve pulmonary arterial hypertension (PAH) and inhibit lung fibrosis in mice by targeting multiple signaling pathways in a recent study.
The research, “Dimethyl Fumarate ameliorates pulmonary arterial hypertension and lung fibrosis by targeting multiple pathways,” was published in the journal Scientific Reports.
The U.S. Food and Drug Administration (FDA) approved Tedfidera, an anti-oxidative and anti-inflammatory agent whose active compound is dimethyl fumarate (DMF), for multiple sclerosis (MS). But studies have shown it helps those with psoriasis, and autoimmune and inflammatory diseases.
But “in contrast to the anti-oxidative and anti-inflammatory effects of DMF, which have been widely studied, the anti-fibrotic effects of DMF remain largely unexplored,” the researchers wrote. So they tested it as a treatment for PAH, using pulmonary cells taken from patients and mouse models of the disease.
A connective tissue disease such as systemic sclerosis is a risk factor for PAH. Patients with such diseases have a poorer response to PAH treatment and greater mortality. That prompted scientists to use a bleomycin mouse model to address DMF’s role in fibrosis. It is the most commonly used model for studying lung fibrosis.
DMF treatment improved PAH by reducing inflammation, oxidative damage, and fibrosis. The results were achieved in experimental in vivo models of PAH and in vitro PAH patient-derived cells. In vivo research involves a living organism. In vitro research occurs in a test tube or other laboratory environment.
“The potent anti-inflammatory and anti-oxidative effects of DMF are of particular relevance as these pathways have been increasingly recognized as being pivotal in PAH pathogenesis,” the researchers wrote.
The team discovered that DMF inhibited key inflammatory pathways, including one mediated by the transcriptional factor NFκB and the signal transducer and transcription activator 3 (STAT3). DMF’s ability to inhibit inflammation led to decreased lung tissue infiltration by macrophages and immune cells in vivo. Macrophages are white blood cells.
DMF caused a significant reduction in pro-fibrotic mediators’ expression, both in vivo and in vitro, researchers found. In fact, DMF inhibited bleomycin-induced up-regulation of several pro-fibrotic genes, preventing the development of pulmonary fibrosis in the bleomycin mouse model.
Overall, the study highlighted DMF’s multiple modes of action and “strongly supports the testing of DMF as a therapy for patients with PAH,” the researchers concluded.