Early Data Support Ability of MicroRNA Mimic, MRG-229, to Treat IPF

Early Data Support Ability of MicroRNA Mimic, MRG-229, to Treat IPF
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New preclinical data support MRG-229, an investigative next-generation treatment for idiopathic pulmonary fibrosis (IPF), as safe and effective, miRagen reported.

“We believe this body of evidence supports further development of MRG-229 as a potentially differentiated approach for the treatment of IPF,” William S. Marshall, PhD, the company’s president and CEO, said in a press release.

MicroRNAs are tiny RNA molecules that — unlike the better known messenger RNAs — do not code for a protein. Instead, microRNAs help to regulate the activity of cells, largely by controlling the activity of genes.

MiR-29 is a microRNA molecule that has been shown to be present at comparatively low levels in people with disorders characterized by fibrosis (scarring), such as IPF.

MRG-229 is a next-generation mimic of miR-29, meaning it was designed to replicate the biological activity of this microRNA.

Data disclosed by miRagen confirmed that miR-29 levels are lower than usual in the lungs of  IPF patients, and that blood levels of this microRNA are significantly associated with survival.

Fibrosis in IPF and other fibrotic diseases is primarily driven by cells called fibroblasts. New preclinical data show that treating fibroblasts with miR-29 mimics in vitro (in a lab setting) significantly reduced the activity of fibrosis-associated molecular pathways in these cells. This includes a decrease in fibroblasts’ production of collagen, a protein that is a major component of scar tissue.

MiR-29 mimics also reduced fibrosis in samples of human lung tissue treated with pro-fibrotic compounds in vitro.

Next-generation miR-29 mimics — specifically, MRG-229 — were also seen to more effectively limit scarring in a mouse model of lung fibrosis, compared with the company’s first-generation miR-29 mimics (like MRG-201, or Remlarsen). This anti-fibrotic activity was evident when the next-generation mimic was administered intravenously (injected into the bloodstream) and subcutaneously (injected under the skin).

Studies in mice also identified some biological markers that may be useful in future lab work or in clinical trials assessing miR-29’s antifibrotic activity.

Data obtained also showed no toxic effects of MRG-229’s use in rats and mice, studied at doses up to 30 mg/kg twice a week for up to four weeks, miRagen reported. Studies are now starting in non-human primates to further investigate its safety profile.

“MRG-229 has demonstrated mechanistic biomarker regulation and antifibrotic activity in vitro using human model systems,” Marshall said. “In addition, subcutaneous administration of the product candidate induced the reversal of pathologic fibrotic gene expression and resulted in a significant reduction of fibrosis in the most commonly employed pre-clinical animal model of pulmonary fibrosis. Finally, high doses of MRG-229 in preclinical toxicology studies in rats showed no clinically significant toxicity.”

Naftali Kaminski, MD, principle investigator on a National Institutes of Health (NIH) grant investigating miR-29 therapies in pulmonary fibrosis, added: “The most recent data, generated as part of our collaboration with miRagen and supported by an NIH CADET grant, is encouraging and suggests that miR-29 replacement may represent a novel paradigm in the treatment of IPF.”

Kaminski is a professor at Yale School of Medicine.

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
Total Posts: 110
Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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