Although associated with a long list of side effects, corticosteroids are still the drugs of choice to treat asthma patients, because of their high efficiency. Nevertheless, also responsive patients develop resistance to the beneficial effect of these steroidal drugs. We previously demonstrated that a combination of steroids with another type of drug, called PPAR agonists, not only improved cellular anti-inflammatory responses, but also kept the blood sugar levels constant. These normally rise upon long-term steroid treatment, ultimately leading to diabetes. Starting from these findings, we wish to
explore whether a combination therapy based on GCs and PPAR agonists may be advantageous to
treat allergic asthma. To this purpose, the house dust mite model is most relevant. We will first look which of the three different PPAR agonist types work best together with the steroids in bronchial epithelial cells derived from asthma patients versus control donors. Next, we will also investigate if PPAR agonists are able to circumvent steroid-driven therapy resistance. Understanding the detailed molecular mechanism how the different receptors triggered by steroids and PPAR agonists interact and how they modulate target genes that contribute to asthmatic responses, or are able to resolve airway inflammation, is our ultimate goal. The gathered insights will be crucial for the ultimate
development of safer and effective drugs that demonstrate fewer side effects.