NCT for therapy and prophylaxis of airborne mycoses

Fungal lung infections are a permanent problem in modern medicine. They occur in patients with deficits in the immune system, mainly caused by tumour therapies or by inborn diseases. Treatment of fungal lung infections with established antimycotics is difficult and frequently not sufficient so that mortality in patients at risk is still high. Therefore, better therapies are urgently needed. N- chlorotaurine (NCT) is a promising candidate for an improved novel therapy. It is originally a body-own compound formed by human defence cells, and we have established its chemical synthesis. NCT has broad-spectrum anti-infective and antiseptic activity without development of resistance, and it is very well tolerated upon topical application in different sensitive body regions. Even inhalation of NCT is possible in humans and animals without noteworthy adverse effects, which renders the substance promising for treatment of infections of the lower airways. Therefore, it is the aim of this project to investigate the activity and mechanisms of action of NCT applied to the lower airways. In particular, compatibility and interaction of NCT with already used antimycotics will be evaluated as well as its influence on the body-own defence system. The susceptibility of main kinds of fungi to plain NCT, its combination with antimycotics, and its combination with components of the human defence system will be tested. Experiments will be done in bronchial fluid, too, to mimic the real environment. Recently, we were able to demonstrate the efficacy of inhaled NCT in fungal pneumonia in the living organism in a mouse model. In the present project, we want to investigate in this in-vivo model if NCT is better as a single therapy or as a combination with established antimycotics, an important question regarding future therapies. The influence of NCT not only on the removal of fungi, but also on the body-own defence system and many other disease parameters will be studied. Therapy of lung mycoses with inhaled NCT as a body-own antiseptic is a highly innovative and promising approach due to high tolerability and efficacy, supported by up to date clinical studies and case applications. The experiments of this project provide the basis for a breakthrough to decrease severity of disease and mortality of patients at risk.