One of the exciting things about the biotechnology industry is its ability to innovate and translate developments in basic science into potential new drugs.
I previously wrote about denufosol in cystic fibrosis (CF), a disease that affects about 30,000 people in the United States and 70,000 worldwide. The disease is characterized by the accumulation of mucus that leads to bacterial overgrowth and chronic lung infections. Mucus cannot be removed from the lung in CF due to abnormal mucociliary transport resulting from impaired epithelial chloride secretion and sodium hyperabsorption. This is now known to be due to defective cystic fibrosis transmembrane regulator (CFTR) protein. A good overview of this can be found in the 2006 New England Journal of Medicine Editorial by Felix Ratjen, “Restoring Airway Surface Liquid in Cystic Fibrosis.”
A good overview of the pipeline of new drugs in development for CF can be found on the Cystic Fibrosis Foundation web site. Vertex in particular has two drugs (VX-809, VX-770) in late stage development that are cystic fibrosis transmembrane conductance regulators, aimed at increasing CFTR function. Phase 3 registration data for VX-770 is expected in the first half of 2011. I look forward to writing about the results.
Recently, a team from Johns Hopkins led by Neeraj Vij published a paper in the January 2011 issue of Journal of Immunology on the “Critical Modifier Role of Membrane-Cystic Fibrosis Transmembrane Conductance Regulator-Dependent Ceramide Signaling in Lung Injury & Emphysema.”
The researchers found that lung damage in mice was associated with changes in the amount of CFTR in the cell surface membrane. Decreases in the amount of CFTR were associated with increased ceramide, a trigger of inflammation of cell-death. Or as the the paper describes it:
“CFTR expression inversely correlates with severity of emphysema and ceramide accumulation in chronic obstructive pulmonary disease subjects compared with control subjects.”
The emergence of inflammation as a key role in chronic disease was the subject of a previous blog post about diabetes, so is interesting to see another area where it is involved.
This basic research shows that developing drugs that target CFTR and mediate ceramide may have an important role to play in the treatment of emphysema, a chronic obstructive pulmonary disease (COPD) that affects 2 million Americans. Translational medicine that can take basic science and apply it to clinical practice is key to the long term success of the biotechnology industry.