New inhaled drug may prevent severe pneumonia

Overactive immune cells are often the cause of lung damage in diseases like COVID-19. Researchers at the Technical University of Munich (Germany) have developed an RNA agent for lung aerosols that slows down the activity of these cells, called macrophages.His research was published in the journal Science “Nature Communications”developed a The RNA-based active substance is called RCS-21 Prevent severe lung inflammation and fibrosis, scarring of lung tissue, such as in SARS-CoV-2 infection. In cells, RCS-21 blocks the activity of microRNA 21 molecules. The research group has long studied this nucleic acid as one of the triggers for the hyperactivity of macrophages in severe lung infections.The team now describes how The active ingredient RCS-21 reaches its target particularly effectively through the inhaler. To do this, the researchers took advantage of the special functions of macrophages.

scavenger cells

These scavenger cells also abundant in healthy lungs. There they perform the important task of destroying bacterial and fungal spores as quickly as possible. Macrophages recognize targets based on, among other things, complex sugar molecules on the invader’s surface. “We determined in single-cell analysis that, on the one hand, the corresponding sugar receptor is one of the most common receptors on macrophages. On the other hand, the receptor is, in a sense, a unique feature of macrophages : they hardly appear elsewhere,” explains Stefan Engelhardt, one of the leaders of the study.That’s why the team combined its active ingredient with a sugar molecule, or more precisely: with triglyceride. So far, this approach has only been applied to active ingredients with less complex chemical compositions. Studies in mice yielded definitive results. “When the drug was administered as an aerosol, the macrophages were able to take up the active substance significantly better than in the absence of sugar molecules. In contrast, other cell types even completely excluded these molecules,” says Christina, first author of the article. Baker explained.

reduce risk

In mouse experiments, RCS-21 reduced microRNA 21 by more than half compared with control animals. Fibrosis and inflammation were also reduced obvious after treatment. RCS-21 treatment also prevented increased microRNA-21 activity in human lung tissue samples laboratory-infected with the SARS-CoV-2 coronavirus.