Cystic fibrosis (CF) is one of the most common autosomal recessive diseases in the human population. CF as a disease typically involves several different epithelial tissues. However, the principal clinical problem resulting in 90% of all CF deaths is that of defective lung function. This disease is a result of mutations in a single gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR is a member of the ATP-binding cassette (ABC) family of transmembrane reporter proteins. Hundreds of different individual CFTR mutations falling into five different functional classes have been identified including missense mutations, frameshifts, in-frame deletions, and splicing mutants.
However, a single mutation resulting in deletion of the phenylalanine at position 508 of the protein (∆F508) accounts for approximately 67% of all known CF patients. This mutation results in improper CFTR protein folding and trafficking such that functional CFTR does not reach the cell membrane surface. Experiments in cell culture that are able to overcome the blockade of this mutant CFTR from reaching the cell surface indicate that if ∆F508 reaches the cell membrane it functions normally.
Dartmouth researchers have discovered that anthracyclines (e.g., doxorubicin, idarubicin) or their metabolites (e.g., doxorubicinal) can increase functional cell surface expression of the ∆F508 mutant CFTR protein and other mutants in this class in CF patients. It is believed therefore that these drugs can be used clinically to treat CF patients, at lower doses than currently used in cancer chemotherapy and at completely non-toxic doses of drug. Gene constructs and cell lines transfected with these constructs have also been identified for CF treatment drug screens.
These findings are claimed in the issued United States Patent No. 7,585,639. We are seeking an industrial partner who is interested in further refinement and commercialization. (Ref: J110)
Last Updated: 7/24/12