Methods for Treatment of Alport Syndrome
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.