Composition for the treatment of cystic fibrosis

Abstract

The present invention provides compositions comprising a prostacyclin or prostacyclin analogue, or a pharmaceutically acceptable salt thereof for use in preventing or treating cystic fibrosis. The invention also provides the use of a kit comprising a prostacyclin or prostacyclin analogue for treating or preventing a condition associated with cystic fibrosis in a subject.

Description

[0001]The present invention provides compositions comprising a prostacyclin or a prostacyclin analogue or a pharmaceutically acceptable salt thereof for use in preventing or treating cystic fibrosis.[0002]Cystic fibrosis (CF) is a genetic disease resulting from mutations in a 230 kb gene on chromosome 7 encoding a 1480 amino acid polypeptide known as the cystic fibrosis transmembrane conductance regulator (CFTR) which serves as a chloride channel in epithelial membranes. Over 1000 mutant alleles have been identified to date. The most common mutation, ΔF508, is the deletion of a phenylalanine residue at codon 508 in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This mutation results in a severe reduction in CFTR function, and leads to the classic cystic fibrosis phenotype characterized with abnormality in exocrine gland functions like raised sweat chloride, recurrent respiratory infection with bronchiectasis, and early-onset of pancreatic insufficiency.[0003...

AI Technical Summary

Benefits of technology

[0016]The object of the invention is achieved by providing a composition comprising a prostacyclin or an analogu

Problems solved by technology

This leads to impaired mucociliary clearance, airway infection, and inflammation characteristic of cystic fibrosis (CF).

A central issue in CF disease is the inability of this common CFTR variant to achieve the native, folded state that will exit from the endoplasmic reticulum (ER) and traffic to the epithelial cell apical membrane.

However, a consensus as to which CFTR subdomains are effective in mutant protein rescue is not apparent, and the mechanism of this effect remains obscure.

Most of these substances, such as forskolin, however, induce a rather unspecific elevation of cAMP, which may have also very harmful effects such as inflammation.

Pulmonary fibrosis, however, is an interstitial lung disease that is caused by the accumulation of collagen fibres in the lung; this restricts the capacity of the lung to inhale air: the lung loses its compliance and the airway resistance increases (compliance=1 / resistance).

If mucociliary breaks down, the bacteria cannot be removed from the bronchi, the bronchi are colonized by bacteria and there are repeated bouts of lung infections that destroy the lung.

Presently, no treatments of cystic fibrosis are available that significantly improve quality of life of patients over a longer period.

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