Novel therapy for improving airway hydration status in cystic fibrosis patients

Novel therapy for improving airway hydration status in cystic fibrosis patients
Credit: Thinkstock

Cystic fibrosis is one of the most common inherited single gene diseases, with an incidence of 1 out of 3,000 newborns in central Europe. An EU study developed a novel gene therapy approach for improving fluid absorption in diseased airways.

is caused by mutations in the (CFTR) gene, which controls the water and salt content of the liquid protecting the lung airways. Cystic fibrotic lungs are characterised by an accumulation of thick secretions due to an abnormal transport of chloride across the lung epithelium.

Delivery of the wild type CFTR gene to the lung epithelium appears to be the most straightforward approach towards gene therapy of cystic fibrosis. However, clinical studies have been met with limited success due to the low transfection levels achieved in vivo.

The EU-funded 'Improved precision of nucleic acid based therapy of cystic fibrosis' (Improved Precision) project was designed to develop a novel therapeutic approach for the treatment of cystic fibrosis by targeting the epithelial (ENaC) of the respiratory epithelium by .

ENaC is believed to play a major role in the pathogenesis of in cystic fibrosis patients as it is regulated by CFTR. It has therefore been suggested that down-regulation of ENaC restores the tissue layer damaged in cystic fibrosis airways, thereby improving mucous clearance in the lung.

The Improved Precision project proposed to administer siRNA constructs via the airways in aerosol form. A further level of precision to the approach was brought about through coupling of these constructs with magnetic nanoparticles. Application of an would then be used to achieve lung-specific accumulation and retention.

After showing over 90% reduction in ENaC synthesis in vitro, the most efficient construct formulation was tested in animal models. The constructs were delivered to the lungs as aerosolised magnetic fine particles by high-gradient magnetic devices.

The observed down-regulation of ENaC expression was concomitant with up to 70 % reduction in channel activity, and lower fluid absorption through the bronchial epithelium for 8 days. These findings clearly indicated the potential of a siRNA approach for improving the airway hydration status in cystic fibrosis patients.

Although the system mandates further optimisation before it can be applied to humans, the Improved Precision project showed promising results towards ameliorating the lung pathology of . Translation of this approach to the clinic will surely benefit many cystic fibrosis sufferers worldwide by improving their quality of life.

add to favorites email to friend print save as pdf

Related Stories

New proteins to clear the airways in cystic fibrosis and COPD

Jul 13, 2012

University of North Carolina scientists have uncovered a new strategy that may one day help people with cystic fibrosis and chronic obstructive pulmonary disorder better clear the thick and sticky mucus that clogs their lungs ...

Unraveling a new regulator of cystic fibrosis

Sep 19, 2011

Cystic fibrosis (CF), a chronic disease that clogs the lungs and leads to life-threatening lung infections, is caused by a genetic defect in a chloride channel called cystic fibrosis transmembrane conductase regulator (CFTR). ...

Cystic fibrosis gene typo is a double whammy

Nov 12, 2010

An imbalance of salt and water in patients with cystic fibrosis makes their lungs clog up with sticky mucus that is prone to infection. The cause of the offending imbalance is a well-known genetic error, one that blocks the ...

Recommended for you

Overwhelmed west Africa ramps up Ebola response

2 hours ago

West Africa intensified its response to the deadly Ebola epidemic on Sunday, with Sierra Leone uncovering scores of dead bodies during a 72-hour shutdown and Liberia announcing hundreds of new hospital beds.

Sierra Leone reaches final day of Ebola lockdown

6 hours ago

Frustrated residents complained of food shortages in some neighborhoods of Sierra Leone's capital on Sunday as the country reached the third and final day of a sweeping, unprecedented lockdown designed to ...

Sierra Leone faces criticism over Ebola shutdown

Sep 20, 2014

Sierra Leone began the second day of a 72-hour nationwide shutdown aimed at containing the spread of the deadly Ebola virus on Saturday amid criticism that the action was a poorly planned publicity stunt.

Presence of peers ups health workers' hand hygiene

Sep 19, 2014

(HealthDay)—The presence of other health care workers improves hand hygiene adherence, according to a study published in the October issue of Infection Control and Hospital Epidemiology.

User comments