Methods for Treatment of Alport Syndrome

Abstract

Provided herein are methods for the treatment of Alport Syndrome, using modified oligonucleotides targeted to miR-21. In certain embodiments, a modified oligonucleotide targeted to miR-21 improves kidney function and/or reduces fibrosis in subjects having Alport Syndrome. In certain embodiments, administration of a modified oligonucleotide targeted to miR-21 delays the onset of end-stage renal disease in a subject having Alport Syndrome. In certain embodiments, a modified oligonucleotide targeted to miR-21 delays the need for dialysis or kidney transplant in a subject having Alport Syndrome.

1 . A method of treating Alport Syndrome comprising administering to a subject having or suspected of having Alport Syndrome a pharmaceutical composition comprising a therapeutically effective amount of a modified oligonucleotide consisting of 19 linked nucleosides and having the structure 5′-A E C S ATC S AGTC S TGAU S AAGC S TA E -3′ (SEQ ID NO: 3), where nucleosides not followed by a subscript are β-D-deoxyribonucleosides; nucleosides followed by a subscript “E” are 2′-MOE nucleosides; nucleosides followed by a subscript “S” are S-cEt nucleosides, and each internucleoside linkage is a phosphorothioate internucleoside linkage, wherein the subject is male and wherein the Alport syndrome is the X-linked form of Alport syndrome. 
     
     
         2 . The method of  claim 1  wherein the subject has been diagnosed as having Alport Syndrome prior to administering the modified oligonucleotide. 
     
     
         3 .- 30 . (canceled) 
     
     
         31 . The method of  claim 1 , wherein the pharmaceutical composition is a sterile aqueous solution. 
     
     
         32 . The method of  claim 1 , comprising measuring blood urea nitrogen in the blood of the subject. 
     
     
         33 . The method of  claim 1 , comprising measuring creatinine in the blood of the subject. 
     
     
         34 . The method of  claim 1 , comprising measuring creatinine clearance in the subject. 
     
     
         35 . The method of  claim 1 , comprising measuring albumin:creatinine ratio in the subject. 
     
     
         36 . The method of  claim 1 , comprising measuring glomerular filtration rate in the subject. 
     
     
         37 . The method of  claim 1 , wherein blood urea nitrogen is reduced in the subject following administration of the pharmaceutical composition. 
     
     
         38 . The method of  claim 1 , wherein creatinine is reduced in the blood of the subject following administration of the pharmaceutical composition. 
     
     
         39 . The method of  claim 1 , wherein creatinine clearance is improved in the subject following administration of the pharmaceutical composition. 
     
     
         40 . The method of  claim 1 , wherein albumin:creatinine ratio is reduced in the subject following administration of the pharmaceutical composition. 
     
     
         41 . The method of  claim 1 , wherein the glomerular filtration rate is improved in the subject following administration of the pharmaceutical composition.