Therapy and kit for the prevention and treatment of cystic fibrosis
A combination therapy and kit including an agent that inhibit the interaction between CAL and mutant CFTR proteins, in combination with a CFTR corrector, CFTR potentiator, mucolytic, anti-inflammatory agent or a combination thereof are provided as is a method for preventing or treating cystic fibrosis.
1. A method for treating cystic fibrosis comprising administering to a subject in need of treatment an effective amount of an agent that selectively inhibits the interaction between a degradation-prone Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and CFTR-Associated Ligand, thereby treating the subject's cystic fibrosis.
2. The method of claim 1 , wherein the degradation-prone CFTR is ΔF508 CFTR or R1066C CFTR.
3. The method of claim 1 , wherein the agent is a small organic compound having the structure of Formula I:
wherein, R 1 , R 2 and R 3 are each independently hydrogen, —OR 4 , lower alkyl, amino, halo, or a carboxyl group; and R 4 is hydrogen or a lower alkyl group.
4. The method of claim 1 , wherein the agent is a peptide comprising the amino acid sequence of SEQ ID NO:1, or a derivative or peptidomimetic thereof.
5. The method of claim 4 , wherein the peptide is derivatized with a label, one or more post-translational modifications, a cell-penetrating sequence, or a combination thereof.
6. The method of claim 1 , further comprising administering a CFTR corrector, CFTR potentiator, mucolytic, anti-inflammatory agent or a combination thereof.
7. A kit comprising
(a) an agent that inhibits the interaction between a degradation-prone Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and CFTR-Associated Ligand (CAL); and
(b) a CFTR corrector, CFTR potentiator, mucolytic, anti-inflammatory agent or a combination thereof.
8. The kit of claim 7 , wherein the agent is a small organic molecule having the structure of Formula I:
wherein, R 1 , R 2 and R 3 are each independently hydrogen, —OR 4 , lower alkyl, amino, halo, or a carboxyl group; and R 4 is hydrogen or a lower alkyl group.
9. The kit of claim 7 , wherein the agent is a peptide comprising the amino acid sequence of SEQ ID NO:1, or a derivative or peptidomimetic thereof.
10. The kit of claim 9 , wherein the peptide is derivatized with a label, one or more post-translational modifications, a cell-penetrating sequence, or a combination thereof.