Methods for treatment of polycystic kidney disease
Provided herein are methods for the treatment of polycystic kidney disease, including autosomal dominant polycystic kidney disease, using modified oligonucleotides targeted to miR-17.
1. A method of treating polycystic kidney disease comprising administering to a subject in need thereof a compound comprising a modified oligonucleotide consisting of 8 to 25 linked nucleosides, wherein the nucleobase sequence of the modified oligonucleotide is complementary to miR-17, wherein the nucleobase sequence of the modified oligonucleotide comprises the nucleobase sequence 5′-GCACTTTG-3′ (SEQ ID NO: 3), wherein each T in the nucleobase sequence is independently selected from a T and a U, wherein the compound consists of the modified oligonucleotide, and wherein the polycystic kidney disease is autosomal dominant polycystic kidney disease.
2. The method of claim 1 wherein the subject has been diagnosed as having polycystic kidney disease prior to administering the modified oligonucleotide.
3. The method of claim 1 , wherein the subject has increased total kidney volume.
4. The method of claim 1 , wherein the subject has hypertension.
5. The method of claim 1 , wherein the subject has impaired kidney function.
6. The method of claim 3 , wherein the total kidney volume is height-adjusted kidney volume.
7. The method of claim 1 , wherein the nucleobase sequence of the modified oligonucleotide is at least 90% complementary, is at least 95% complementary, or is 100% complementary to the nucleobase sequence of miR-17 (SEQ ID NO: 1).
8. The method of claim 1 , wherein the modified oligonucleotide consists of 8, 9, 10, 11 or 12 linked nucleosides.
9. The method of claim 1 , wherein the modified oligonucleotide consists of 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 linked nucleosides.
10. The method of claim 1 , wherein the modified oligonucleotide consists of 15, 16, 17, 18, 19, 20, 21, or 22 linked nucleosides.
11. The method of claim 1 , wherein the modified oligonucleotide consists of 17, 18, 19, 20, 21, 22, or 23 linked nucleosides.
12. The method of claim 1 , wherein the modified oligonucleotide comprises at least one modified nucleoside.
13. The method of claim 12 , wherein the modified nucleoside is selected from an S-cEt nucleoside, a 2′-O-methoxyethyl nucleoside, and an LNA nucleoside.
14. The method of claim 1 , wherein each internucleoside linkage of the modified oligonucleotide is a modified internucleoside linkage.
15. The method of claim 14 , wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage.