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 modified oligonucleotide consisting of 15 to 22 linked nucleosides, wherein the nucleobase sequence of the modified oligonucleotide is at least 90% complementary to miR-21.
2. The method of claim 1 , wherein the nucleobase sequence of the modified oligonucleotide is at least 95% complementary to the nucleobase sequence of miR-21 (SEQ ID NO: 1).
3. The method of claim 1 , wherein the modified oligonucleotide comprises at least one modified nucleoside.
4. The method of claim 3 , wherein the modified nucleoside is selected from an S-cEt nucleoside, a 2′-O-methoxyethyl nucleoside, and an LNA nucleoside.
5. The method of claim 1 , wherein the modified oligonucleotide comprises at least one modified internucleoside linkage.
6. The method of claim 1 , wherein each internucleoside linkage of the modified oligonucleotide is a modified internucleoside linkage.
7. The method of claim 6 , wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage.
8. The method of claim 6 , wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage.
9. The method of claim 1 , wherein the nucleobase sequence of the modified oligonucleotide is 100% complementary to the nucleobase sequence of miR-21.
10. The method of claim 1 , wherein the modified oligonucleotide consists of 19 linked nucleosides.