Compositions and methods for modulating growth hormone receptor expression
The present embodiments provide methods, compounds, and compositions for treating, preventing, or ameliorating a disease associated with excess growth hormone using antisense compounds or oligonucleotides targeted to growth hormone receptor (GHR).
1. A compound comprising a modified oligonucleotide and a conjugate group, wherein the modified oligonucleotide consists of 16 linked nucleosides having the nucleobase sequence of SEQ ID NO: 2122, wherein each cytosine of the modified oligonucleotide is a 5-methylcytosine; each internucleoside linkage of the modified oligonucleotide is a phosphorothioate linkage; the modified oligonucleotide comprises the sugar motif eekddddddddddkke (5′ to 3′), wherein ‘k’ indicates a cEt sugar moiety, ‘d’ indicates a 2′-deoxyribose, and ‘e’ indicates a MOE sugar moiety; and the conjugate group is attached to the 5′-end of the modified oligonucleotide and comprises:
2. A composition comprising the compound of claim 1 , or salt thereof, and a pharmaceutically acceptable carrier or diluent.
3. The composition of claim 2 , wherein the pharmaceutically acceptable diluent is water or phosphate buffered saline.
4. The composition of claim 3 , wherein the pharmaceutically acceptable diluent consists essentially of water.
5. A method comprising administering to an animal the compound of claim 1 .
6. A method comprising administering to an animal the composition of claim 2 .
7. A method comprising administering to an animal the composition of claim 3 .
8. A method comprising administering to an animal the composition of claim 4 .
9. The method of claim 5 , wherein the animal is a human.
10. The method of claim 6 , wherein the animal is a human.
11. The method of claim 7 , wherein the animal is a human.
12. The method of claim 8 , wherein the animal is a human.
13. A method of treating a disease associated with excess growth hormone in a human comprising administering to the human a therapeutically effective amount of the compound of claim 1 , thereby treating the disease.
14. A method of treating a disease associated with excess growth hormone in a human comprising administering to the human a therapeutically effective amount of the composition of claim 2 , thereby treating the disease.
15. A method of treating a disease associated with excess growth hormone in a human comprising administering to the human a therapeutically effective amount of the composition of claim 3 , thereby treating the disease.
16. A method of treating a disease associated with excess growth hormone in a human comprising administering to the human a therapeutically effective amount of the composition of claim 4 , thereby treating the disease.
17. The method of claim 13 , wherein the disease is acromegaly.
18. The method of claim 14 , wherein the disease is acromegaly.
19. The method of claim 15 , wherein the disease is acromegaly.
20. The method of claim 16 , wherein the disease is acromegaly.