An inhaled version of miRagen Therapeutics‘ potential fibrosis therapy MRG-201 rendered genes involved in scarring nearly inactive in a rat model of lung fibrosis, the company reported.
The preclinical-trial study also showed that most of the compound reached the animals’ lungs. The fact that little of it was found in other tissue indicates its side effects may be minimal.
MiRagen presented findings on the study at the European Respiratory Society International Congress in Milan, Sept. 9-12. It was in the form of a poster presentation titled “Feasibility, distribution, and efficacy of an inhaled oligonucleotide mimic of miR-29 for pulmonary fibrosis induced by bleomycin in rats.”
The company partnered with the Lovelace Biomedical Research Institute on the study, which looked at how the compound held up after being delivered, the size of the particles in the inhalant, the dose, and where the therapy ended up.
MRG-201 targets microRNA, small molecules of RNA that play a role in gene expression — or genes’ creation of proteins and other functional products.
In the study, researchers exposed rats’ airways exposed to bleomycin, a chemical that triggers fibrosis. The rates then received MRG-201 through a nose inhalant.
The inhalant delivery system produced a fine mist of MRG-201. The fact that the drug’s chemical properties held up after delivery showed that the inhalation system is a suitable way to administer it.
Importantly, the study showed that multiple administrations of MRG-201 reduced the activity of genes involved in the development of fibrosis in the rats.
“We are encouraged by these preclinical inhalation feasibility results for MRG-201, which we believe offer an innovative approach for the potential treatment of pulmonary fibrosis,” William S. Marshall, miRagen’s president and CEO, said in a press release.
“Patients suffering from pulmonary fibrosis have limited treatment options, and this data demonstrates our commitment to developing a safe and effective therapy to treat this debilitating disease,” Marshall added.
MRG-201 mimics the actions of microRNA-29, which researchers think is involved in fibrosis development. This idea is supported by studies showing that patients with idiopathic pulmonary fibrosis (IPF) have abnormally low levels of microRNA-29, which promotes fibrosis by controlling gene activity.
Researchers think this genetic regulation enables MRG-201 to control the production of extracellular matrix, which is composed of collagen and other molecules involved in the build-up of fibrosis.
In addition to lung fibrosis, miRagen is developing MRG-201 to treat skin fibrosis. It recently completed a Phase 1 clinical trial (NCT02603224) of its use against that condition. The treatment lowered the activity of fibrosis-related genes, similarly to what researchers observed in the rat study.
“While we continue to advance MRG-201 in clinical development for the treatment of cutaneous fibrosis, we are excited to further explore its potential utility in pulmonary fibrosis,” Marshall concluded.