Drug-repositioning indicates a way to conquest corticosteroid-insensitivity

Abstract

Recent advance of medications and devices brings more effective treatment intervention to the patients with asthma. As far as obeying guidelines, approximately 90% of patients with asthma acquire good control. However, there are still small number of patients with asthma who resist conventional treatment. Most of them are corticosteroid-insensitive. It would be thought that there are two ways to deal with this problem. The first one is biologics. However, these are very expensive. The second way is a treatment intervention focusing on cancellation of corticosteroid-resistance. In early 2010s, a new-intracellular signaling pathway (phosphatydilinositol-3-kinese: PI3K pathway) is proven to be closely associated with corticosteroid-resistance. PI3K-inhibitor should be one of the promising candidates to attenuate corticosteroid-resistance. But PI3K-inhibitor also has a toxicity when given systemically. Drug-repositioning (DR) is a good option to deal with it. To find out PI3K-inhibitor from numerous medicines gives an answer how to inhibit PI3K pathway. The presenter has found both low-dose theophylline and long-acting beta-2 agonist have a potential to antagonize PI3K. These medicines have been prescribed for decades and their safety has already been proved. It is possible for clinicians to inhibit PI3K activation in patients with asthma associated with corticosteroid-resistance using these medicines without waiting for development of bran-new PI3K inhibitors. DR revealed that nortriptyline acts as a steroid-enhancer via its anti-PI3K activity. Calcium-channel blocker saves lung function in patients with asthma in long-term observation. DR promises us to find cheap and safe options to treat difficult asthma by inhibiting specific intracellular signaling pathways.