network of airways
Diagramatic representation of the conducting airways of the bronchial tree and the alveolar region that they supply.

The bronchial tree is the network of airways that take air to and from the mouth/nose to the alveolar area of the lung for oxygen uptake (Bronchial Tree).

The lungs have developed the mucociliary clearance (MCC) system (MCC image), which is the primary and “perhaps most quantitatively important innate defense mechanism in the lung” (Livraghi & Randell, 2011).

The role of MCC is to trap and remove inhaled materials from the lung. A key component of this system is a thin mucous layer that lines the walls of the airways. MCC constantly moves mucus up to the mouth so that any trapped material is removed from the lung by coughing or by being swallowed. In CF, a mutation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene causes dehydration the Periciliary Fluid (PCF) and produces thick sticky mucus that reduces the efficiency of the MCC system.

 

MCC Normal

 

Diagramatic representation of the MCC system in healthy individuals. Click on image for higher resolution.

 

 

 

CFF MCC

 

The MCC is degraded in CF due to the dehydration of the periciliary and mucus layers. Click on image for higher resolution.

 

Through a series of experiments Lamellar has repeatedly shown the ability of LamellasomeTM technology  to alter the fluidity of sticky mucus (Mucin video) and as presented above in particular they  increased the fluidity of human mucus from the mouth that had been rendered sticky and immobile by radiotherapy (Beatson RIX study).

Based on these findings The West of Scotland CF centre is working with Lamellar to develop LamellasomeTM-based nebulised therapy for CF (PMB/1-nn). A highly detailed pre-clinical and clinical research program is being undertaken for PMB/1-nn).

The pre-clinical work is being supported by a £430k SMART grant from Scottish Enterprise. Preliminary observations include a reduction in the number and size of lamellar bodies in CF (see image).

Note large and multiple lamellar bodies from non CF patient (left image) compared to fewer and smaller lamellar bodies from a CF patient (right image). Click image to enlarge.
Above: Note large and multiple lamellar bodies from non CF patient (left) compared to fewer and smaller lamellar bodies from a CF patient (right). Click image to enlarge.

CF is a genetically inherited disease which affects at least 80,000 people. Given this low prevalence, CF is defined as an orphan drug indication. Lamellar has EU Orphan Drug status for PMB/1-nn for CF and will apply for US Orphan Drug Status after the completion of the SAD/MAD study. The market for treatments in Cystic Fibrosis is currently worth in excess of $2.0 billion per annum.

CF Reference:

Livraghi A, Randell SH. Cystic fibrosis and other respiratory diseases of impaired mucus clearance. Toxicol Pathol. 2007 Jan;35(1):116-29.