Methods and compositions using klotho variant polypeptides

Abstract

The present disclosure is directed to compositions and methods related to an alpha sKlotho variant or fragment, in which 1 to up to about 20 amino acids have been deleted from the C-terminus, optionally also having mutations at V563 and/or K795. The present disclosure also pertains to an alpha sKlotho polypeptide variant or fragment, having mutations at V563 and/or K795, wherein the polypeptide variant or fragment is full-length, or optionally 1 to up to about 20 amino acids have been deleted from the C-terminus. The present disclosure also pertains to fusion polypeptides comprising: (a) an alpha sKlotho, in which 1 to up to about 20 amino acids have been deleted from the C-terminus, optionally also having mutations at V563 and/or K795; (b) a linker; and (c) FGF23, optionally having a mutation at R179, C206 and/or C244, or (c) serum albumin.

1 - 34 . (canceled) 
     
     
         35 . A method of treating or preventing a Klotho-related disease, comprising the step of administering to an individual in need thereof a therapeutically effective dose of a composition comprising an alpha sKlotho, in which about 20 amino acids have been deleted from the C-terminus, optionally also having mutations at V563 and/or K795. 
     
     
         36 . (canceled) 
     
     
         37 . The method of  claim 35  or  36 , wherein the Klotho-related disease is selected from the group consisting of: an age-related condition, a metabolic disorder, hyperphosphatemia, calcinosis, chronic renal disease, chronic renal failure, cancer, breast cancer, and muscle atrophy. 
     
     
         38 . The method of  claim 37 , wherein the age-related condition is selected from the group consisting of sarcopenia, skin atrophy, muscle wasting, brain atrophy, atherosclerosis, arteriosclerosis, pulmonary emphysema, osteoporosis, osteoarthritis, immunologic incompetence, high blood pressure, dementia, Huntington's disease, Alzheimer's disease, cataracts, age-related macular degeneration, prostate cancer, stroke, diminished life expectancy, memory loss, wrinkles, impaired kidney function, and age-related hearing loss. 
     
     
         39 . The method of  claim 38 , wherein the metabolic disorder is selected from the group consisting of Type II Diabetes, Metabolic Syndrome, hyperglycemia, and obesity.