Cystic Fibrosis (“CF”) is the most common autosomal recessive
disorder in Europe and the USA, impacting one in every 2500 children born in
western countries. It is a genetic disease caused by mutations of the CF
transmembrane conductance regulator protein (“CFTR”). While this genetic mutation leads to
several respiratory, reproductive and gastrointestinal complications, the
primary cause of morbidity and mortality in these subjects results from the
destructive effects of chronic pulmonary colonization with Pseudomonas aeruginosa (“P. aeruginosa”).
P. aeruginosa infection of epithelial
cells is initiated by contact of the pathogen with the cell surface. Therefore,
identification of the molecular factors that makes CF patients highly
susceptible to infection by P.
aeruginosa, is critical to the development of new strategies for the
treatment and prevention of CF. Dr. Edward Schuchman and collaborators at the
University of Duisburg-Essen and Weizmann Institute have recently shown that the
lipid ceramide is elevated in the bronchial epithelial cells of the CF patients,
leading to enhanced binding of P.
aeruginosa to CF respiratory epithelial cells. Dr. Schuchman and his colleagues also
showed that administering an inhaled version of the enzyme, acid ceramidase
(AC), which hydrolyzes ceramide in CF mouse models, prevented infection of P. aeruginosa. Therefore, AC can be used in the
treatment of CF to enhance existing therapies and to prevent infection by this
and perhaps other pathogens.
Patent Status: Patent