Small molecule compounds to potentiate most common type of CFTR mutation in cystic fibrosis patients.
Potentiates ΔF508-hCFTR mutation, addressing more than 60 percent of CF patients.
Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and ion channel that malfunctions in the genetic disorder cystic fibrosis (CF) and is implicated in chronic obstructive pulmonary disease (COPD), secretory diarrhea, and chronic pancreatitis, as well. About 30,000 people are living with CF in the United States and 1,000 new cases are diagnosed annually. CF leads to thick viscous mucus in the lungs and repeated respiratory infections. Common treatments of CF include chest physiotherapy, therapies to thin mucus in the lungs and therapies to treat the recurrent infections, but these do not treat the underlying cause of CF. Currently, the only drug available that improves CFTR function works on a specific CFTR mutation which accounts for 4-5% of cases. There are currently no approved drugs that improve the function of the CFTR for majority of CF patients.
The inventors have identified compounds that potentiate the most common CFTR mutation found in cystic fibrosis patients (ΔF508-hCFTR). These two compounds were chosen for study and tested for their effects on wild type CFTR channels from human, mouse, and frog and on ΔF508-hCFTR, the most common mutation found in cystic fibrosis patients in the United States. Both compounds showed species-dependent effects on the wild-type CFTR channels and both compounds potentiated ΔF508-hCFTR better than existing clinical therapeutics. When administered, these drugs lead to a restoration in channel function of more than 60 percent. The CFTR is also a target for other diseases such as chronic obstructive pulmonary disease, chronic pancreatitis and diarrhea.
In vitro proof of concept and electrophysiology data is available. Additional validation studies for these compounds are currently underway.
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