Methods for modulating kallikrein (KLKB1) expression
Disclosed herein are methods for decreasing kallikrein and treating or preventing inflammatory conditions in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to kallikrein include hereditary angioedema (HAE). Methods for inhibiting kallikrein can also be used as a prophylactic treatment to prevent individuals at risk for developing an inflammatory condition, such as, hereditary angioedema.
1. A method comprising, prophylactically treating hereditary angioedema (HAE) in an animal identified as having HAE by administering to the animal a therapeutically effective amount of a compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides, wherein the modified oligonucleotide is at least 90% complementary to a KLKB1 nucleic acid.
2. The method of claim 1 , wherein the prophylactic administering of the compound comprising a modified oligonucleotide prevents or ameliorates edema.
3. The method of claim 1 , wherein the prophylactic administering of the compound comprising a modified oligonucleotide prevents or ameliorates vascular permeability.
4. The method of claim 1 , wherein the prophylactic administering of the compound comprising a modified oligonucleotide prevents or ameliorates vascular leakage.
5. The method of claim 1 , wherein the prophylactic administering of the compound comprising a modified oligonucleotide prevents or ameliorates inflammation.
6. The method of claim 1 , wherein the animal is a human.
7. The method of claim 1 , wherein the KLKB1 nucleic acid is a human KLKB1 nucleic acid.
8. The method of claim 7 , wherein the human KLKB1 nucleic acid is SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or the complement of SEQ ID NO: 10.
9. The method of claim 8 , wherein the modified oligonucleotide is 100% complementary to a human KLKB1 nucleic acid.
10. The method of claim 9 , wherein the modified oligonucleotide is a single-stranded oligonucleotide.
11. The method of claim 10 , wherein the modified oligonucleotide comprises at least one modified internucleoside linkage.
12. The method of claim 11 , wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage.
13. The method of claim 8 , comprising at least one nucleoside having a modified sugar.
14. The method of claim 13 , wherein the modified sugar is a bicyclic sugar.
15. The method of claim 14 , wherein the bicyclic sugar comprises a 4′-CH(CH 3 )—O-2′ bridge.
16. The method of claim 13 , wherein the modified sugar comprises a 2′-O-methoxyethyl group.
17. The method of claim 8 , wherein at least one nucleoside comprises a modified nucleobase.
18. The method of claim 17 , wherein the modified nucleobase is a 5-methylcytosine.
19. The method of claim 8 , comprising co-administering the compound comprising a modified oligonucleotide and any of the group selected from a serine protease inhibitor Cl-INH recombinant protein, CINRYZE, BERINERT, KALBITOR, Icatibant, Ecallantide, attenuated androgens, anabolic steroids, antifibrinolytic agents, epsilon-aminocaproic acid, tranexamic acid.
20. The method of claim 8 , wherein the administering is parenteral administration.
21. The method of claim 20 , wherein the parenteral administration is any of subcutaneous or intravenous administration.
22. The method of claim 8 , wherein the compound comprises a conjugate.