Pyrophosphate Stimulates CFTR Chloride Channels (95-008)
University of Iowa Research Foundation
Contact
Shannon Sheehan
Shannon_Sheehan@uiowa.edu
319-335-4605
Background
Cystic fibrosis is an inherited chronic disease that affects the lungs and digestive system of about 30,000
children and adults in the United States and 70,000 individuals worldwide. Cystic fibrosis is caused by a
mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Structurally, CFTR is an
ATP-binding cassette (ABC) gene which creates a protein that is anchored to the outer membrane of cells in
the sweat glands, lungs, and pancreas. When functioning properly, the protein acts like a channel that
connects the cytoplasm to the surrounding fluid. In cystic fibrosis patients, chloride is trapped inside the cells,
and the body ends up producing unusually thick mucus that can clogs the lungs, obstructs the pancreas, and
prevent natural enzymes from helping the body break down and absorb food.
Technology
Scientists at the University of Iowa have developed a new drug as well as a regimen for treating/preventing
cystic fibrosis and other diseases associated with insufficient ABC protein activity. The pharmaceutical
composition is an aerosolized pyrophosphate that is accessible to ABC proteins. When administered in a
sufficient amount, this pyrophosphate not only stimulates the protein channels that are blocked in cystic
fibrosis patients but also keeps those channels open. The pyrophosphate has been tested on three different
cystic fibrosis mutations – F508, R117h, and G551S – with a measurable effect on CFTR stimulation
demonstrated in each.
Advantages
Applying pyrophosphate to stimulate CFTR holds considerable promise for cystic fibrosis patients and others
with ABC-associated diseases. This technology:
•
Provides new compositions and therapies for treating diseases or conditions associated
with inappropriate or inadequate activity of ABC proteins.
•
Tremendous promise as a treatment for cystic fibrosis patients, as well as a preventive
measure for those susceptible to the disease
Relevant Research
Carson MR, Winter MC, Travis SM, Welsh MJ. Pyrophosphate stimulates wild-type and mutant CF transmembrane conductance regulator Cl- channels. J Biol Chem. 95;270(35): ncbi.nlm.nih.gov/pubmed/7544788.
Patent Links (2)
http://www.google.com/patents/US5686114?printsec=abstract&dq=5686114&ei=qxjaT8y0EqW42wXK6dX
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http://www.google.com/patents/US5958907?printsec=abstract&dq=5958907&ei=BSDaT5L9Bcjm2gXOytn
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