Cystic Fibrosis (CF) CFTR Mutation Biobank Program

 

Research Study: Cystic Fibrosis (CF) is an autosomal recessive disorder due to a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR).  CFTR is a chloride channel where gene mutations cause a defect in chloride conduction at airway surface epithelial cells leading to bacterial biofilm formation. Chronic bacterial biofilm formation leads to recurrent airway infections and ultimately to chronic lung disease and respiratory failure.  There is no cure for CF-related lung disease or universal treatment to correct all CFTR mutations. Until recently, historic treatment for CF has relied on supportive measures.  Yet, recent small molecule CFTR modulators like lumacaftor and ivacaftor represent the first attempt to rescue the aberrant function of CFTR mutations.  However, current CFTR modulator agents are only approved for approximately 50 percent of CF patients.  There are over 2000 specific CF mutations, which will make it very challenging to find new CFTR modulator drugs. 

 

In order to identify future CF therapies to correct CFTR, a diverse cell repository of CF-specific stem cell models are needed.  Currently, CF drugs use airway epithelial cells from discarded lungs at the time of death or at the time of lung transplantation.  However, there are significant limitations of these types of cells.  First, there are limited available donated lungs.  Second, the cell lines exhibit an end-stage cell disease state.  Third, the cell lines have limited growth capacity.  Fourth, these cell lines typically ignore younger and earlier-staged disease.

The Institute is currently developing a diverse biorepository of CF-specific stem cell models for performing drug development.  The ultimate objective of this research is to apply stem cell technologies to develop more diverse airway epithelial cell lines from CF patients for preclinical drug discovery.  The multiplicity of genetic mutations in the CFTR gene illustrates the need for a broad biobank of CF cells. The Institute has developed a first in class virus-free and oncogene-free induced pluripotent stem cells (iPSC), which can convert into lung cells. Not all IPSC technologies are the same.  Earlier technologies used viruses and oncogenes to produce these cells.  However, viruses and oncogenes can skew drug responses in these cells, which leads to less predictive drug outcomes.  

To advance this research, we need CF patients with a variety of CFTR mutations sign up on our patient registry.  Patients selected to participate in the research will be asked to provide medical records to confirm their diagnosis and type of CFTR mutation. Also, a blood sample will be collected and shipped to the Institute for further processing.  The research represents a collaboration between the Institute and the University of Minnesota and University of Pittsburg Cystic Fibrosis Centers.

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