A potential treatment for cystic fibrosis has been identified in mice, according to a study published online in Nature Medicine.
Patients with cystic fibrosis have a thick layer of mucus along the linings of their lungs, leading to increased bacterial infections and death. The disease is caused by a mutation in an ion transporter expressed at the cell surface. A leading idea in the field is that reduced ion transport in the lungs leads to cell dehydration and to the accumulation of more viscous mucus, allowing bacteria to evade the immune system.
Working with two mouse models of cystic fibrosis, Erich Gulbins and colleagues found that improper ion transport in the lung has a very different effect -- it raises the pH of intracellular vesicles, modifying the activity of two enzymes that control the level of the lipid ceramide. Over time, ceramide levels increased in the mice lungs, leading to cell death and to inflammation -- two known effects of excess ceramide that, in this case, promoted bacterial infection in the lung.
The authors show that, when an enzyme involved in ceramide metabolism was blocked in the mice, the levels of the lipid were normalized, and bacterial infection and mortality rates were reduced.
As a drug that reduces ceramide levels - amitriptyline - is currently used to treat depression, it could also be used to treat patients with cystic fibrosis.
Erich Gulbins (University of Duisburg-Essen, Germany)
Abstract available online
(C) Nature Medicine press release.
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