Accesory cholera enterotoxin and analogs thereof as activators of calcium dependent chloride channel
AssigneeUniversity of Maryland, Baltimore
InventorMichele Trucksis
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Abstract
Vibrio cholerae accessory cholera enterotoxin (ACE) activates a calcium dependent chloride channel. Ace and Ace analogs can be administered to patients to treat diseases involving defects in chloride secretion by the cystitis fibrosis transmembrane receptor (CFTR). Cystic fibrosis, Dent's disease, X-linked nephrolithiasis, X-linked recessive hypophosphatemic rickets, autosomal dominant myotonia congenita and autosomal recessive general myotonia can be treated by the administration of Ace or an Ace analog. For cystic fibrosis, administration of Ace or an Ace analog increases chloride secretion in the lungs which increases the amount of airway surface water in the lumen of the lungs.
Claims49
A method for treating a disease characterized by a cystic fibrosis transmembrane regulator having decreased activity compared to normal cystic fibrosis transmembrane regulator, said method comprising:
- administering a therapeutically effective amount of a polypeptide to said animal having said disease, wherein said polypeptide activates the calcium-dependent chloride channel.
A method for treating cystic fibrosis comprising:
- administering a therapeutically effective amount of a polypeptide to said animal having said cystic fibrosis, wherein said polypeptide activates the calcium-dependent chloride channel.
A method for treating cystic fibrosis comprising:
- administering a therapeutically effective amount of Ace to an animal having cystic fibrosis.
A method for treating cystic fibrosis comprising:
- administering a therapeutically effective amount of an Ace analog to an animal having cystic fibrosis.
A method for increasing the amount of airway surface water in the lungs of an animal. comprising:
- administering a polypeptide to said animal, wherein said polypeptide activates the calcium-dependent chloride channel.
A method for increasing the amount of airway surface water in the lungs of an animal having a disease characterized by a cystic fibrosis transmembrane regulator having decreased activity compared to normal cystic fibrosis transmembrane regulator, said method comprising:
- administering a polypeptide to said animal having said disease, wherein said polypeptide activates the calcium-dependent chloride channel.
A method for increasing ciliary activity in the lungs of an animal having reduced ciliary activity wherein said reduced ciliary activity is caused, in part, by having a cystic fibrosis transmembrane regulator having decreased activity compared to nonnal cystic fibrosis transmembrane regulator, said method comprising:
- administering a polypeptide to said animal having said reduced ciliary activity, wherein said polypeptide activates the calcium-dependent chloride channel.
A method for increasing ciliary activity in the lungs of an animal having reduced ciliary activity wherein said reduced ciliary activity results from a decrease in the amount of chloride being secreted from bronchial epithelial cells, said method comprising:
- administering Ace to said animal having said reduced ciliary activity.
A method for increasing ciliary activity in the lungs of an animal having reduced ciliary activity wherein said reduced ciliary activity results from a decrease in the amount of chloride being secreted from bronchial epithelial cells, said method comprising:
- administering an Ace analog to said animal having said reduced ciliary.
A method for increasing chloride secretion from bronchial epithelial cells in the lungs of an animal having reduced chloride secretion from bronchial epithelial cells, said method comprising:
- administering a polypeptide that activates the calcium-dependent chloride channel to said animal having reduced chloride secretion from bronchial epithelial.
A method for increasing chloride secretion from cells in an animal having a disease characterized by having reduced chloride secretion from cells, said method comprising:
- administering a polypeptide to said animal having said disease.
A polypeptide encoding for K43*, an Ace analog, in SEQ ID NO:
- 5.
A polypeptide encoding for K21A, an Ace analog, in SEQ ID NO:
- 8.
A polypeptide encoding for E28A, an Ace analog, in SEQ ID NO:
- 10.
A polypeptide encoding for MT1, an Ace analog, in SEQ ID NO:
- 17.
A polypeptide encoding for MT2, an Ace analog, in SEQ ID NO:
- 18.
A polypeptide encoding for MT3, an Ace analog, in SEQ ID NO:
- 19.
A composition comprising at least one polypeptide that activates the calcium-dependent chloride channel and at least one inhalation adjuvant.
A pharmaceutical composition for the treatment of a disease characterized by a decrease of chloride secretion by the cystic fibrosis transmembrane regulator, said composition comprising:
- the polypeptide Ace (SEQ ID NO:
- 2);
- and
- a pharmaceutical acceptable carrier.
A pharmaceutical composition for the treatment of a disease characterized by a decrease of chloride secretion by the cystic fibrosis transmembrane regulator, said composition comprising:
- an Ace analog;
- and
- a pharmaceutical acceptable carrier.
Dependencies are inferred from the claim text.