Methods for treating hypercholesterolemiaDisclosed herein are antisense compounds and methods for decreasing LDL-C in an individual having elevated LDL-C. Additionally disclosed are antisense compounds and methods for treating hypercholesterolemia, or alternatively for treating or preventing atherosclerosis. Further disclosed are antisense compounds and methods for decreasing coronary heart disease risk. Such methods include administering to an individual in need of treatment an antisense compound targeted to a PCSK9 nucleic acid. The antisense compounds administered include gapmer antisense oligonucleotides.Compound that comprises modified oligonucleotides, the nucleosides that this modified oligonucleotides is connected by 12-30 is formed and is had a following nuclear base sequence, described nuclear base sequence comprise by with the component of at least 8 continuous kernel based compositions of following isometric part complementary: seq id no:1's294-317,406-440,406-526,410-436,410-499,446-526,545-581,591-619,591-704,591-743,595-622,600-626,600-639,600-670,601-628,602-628,603-630,611-636,620-647,638-665,648-674,657-684,705-743,782-810,821-859,835-859,835-917,835-942,860-887,860-899,860-909,860-917,869-895,878-905,888-909,923-952,960-1034,960-1173,960-986,967-991,970-1023,970-1064,970-1117,970-996,977-1004,985-1011,989-1016,992-1019,997-1024,997-1024,998-1025,999-1026,1000-1027,1001-1028,1002-1029,1003-1029,1004-1029,1005-1029,1006-1029,1007-1034,1036-1061,1045-1072,1076-1096,1088-1115,1098-1123,1200-1251,1210-1237,1219-1245,1228-1251,1273-1444,1295-1316,1318-1345,1328-1354,1337-1361,1344-1371,1354-1377,1380-1406,1389-1416,1400-1426,1409-1434,1465-1491,1465-1602,1474-1499,1482-1519,1513-1540,1523-1549,1526-1602,1526-1624,1532-1558,1541-1568,1552-1579,1560-1587,1561-1589,1564-1591,1565-1592,1566-1592,1567-1592,1570-1597,1571-1599,1605-1706,1628-1706,1640-1666,1672-1698,1681-1706,1735-1761,1735-1765,1740-1765,1849-1876,1849-1879,1850-1877,1851-1877,1852-1878,1852-1879,1853-1879,1854-1879,1905-1955,1915-1942,1916-1943,1917-1944,1918-1945,1919-1946,1920-1939,1920-1947,1921-1948,1922-1949,1923-1950,1924-1951,1925-1952,1926-1952,1927-1952,1928-1955,1962-2059,2040-2126,2100-2126,2100-2139,2100-2206,2101-2126,2305-2332,2305-2354,2306-2333,2307-2334,2308-2334,2309-2334,2310-2334,2410-2434,2504-2528,2509-2528,2582-2625,2606-2668,2828-2855,2832-2851,2900-2927,2900-2929,2902-2927,2983-3007,2983-3013,3227-3252,3227-3456,3472-3496 or 3543-3569and the nuclear base sequence of wherein said modified oligonucleotides and seq id no:1 at least 90% complementation.
고콜레스테롤혈증을 치료하는 방법본 발명은 상승된 LDL-C를 가진 개체에서 LDL-C를 감소시키기 위한 안티센스 화합물 및 방법에 관한 것이다. 또한, 본 발명은 고콜레스테롤혈증의 치료, 또는 선택적으로 동맥경화증을 치료 또는 예방하기 위한 안티센스 화합물 및 방법에 관한 것이다. 또한 본 발명은 관상동맥질환 위험을 감소시키기 위한 안티센스 화합물 및 방법에 관한 것이다. 상기 방법은 PCSK9 핵산을 표적하는 안티센스 화합물을 처리가 요구되는 개체에 투여하는 것을 포함한다. 투여된 안티센스 화합물들은 갭머 안티센스 올리고뉴클레오타이드들을 포함한다. 12 내지 30개의 연결된 뉴클레오사이드로 이루어지고 SEQ ID NO: 1의 294-317, 406-440, 406-526, 410-436, 410-499, 446-526, 545-581, 591-619, 591-704, 591-743, 595-622, 600-626, 600-639, 600-670, 601-628, 602-628, 603-630, 611-636, 620-647, 638-665, 648-674, 657-684, 705-743, 782-810, 821-859, 835-859, 835-917, 835-942, 860-887, 860-899, 860-909, 860-917, 869-895, 878-905, 888-909, 923-952, 960-1034, 960-1173, 960-986, 967-991, 970-1023, 970-1064, 970-1117, 970-996, 977-1004, 985-1011, 989-1016, 992-1019, 997-1024, 997-1024, 998-1025, 999-1026, 1000-1027, 1001-1028, 1002-1029, 1003-1029, 1004-1029, 1005-1029, 1006-1029, 1007-1034, 1036-1061, 1045-1072, 1076-1096, 1088-1115, 1098-1123, 1200-1251, 1210-1237, 1219-1245, 1228-1251, 1273-1444, 1295-1316, 1318-1345, 1328-1354, 1337-1361, 1344-1371, 1354-1377, 1380-1406, 1389-1416, 1400-1426, 1409-1434, 1465-1491, 1465-1602, 1474-1499, 1482-1519, 1513-1540, 1523-1549, 1526-1602, 1526-1624, 1532-1558, 1541-1568, 1552-1579, 1560-1587, 1561-1589, 1564-1591, 1565-1592, 1566-1592, 1567-1592, 1570-1597, 1571-1599, 1605-1706, 1628-1706, 1640-1666, 1672-1698, 1681-1706, 1735-1761, 1735-1765, 1740-1765, 1849-1876, 1849-1879, 1850-1877, 1851-1877, 1852-1878, 1852-1879, 1853-1879, 1854-1879, 1905-1955, 1915-1942, 1916-1943, 1917-1944, 1918-1945, 1919-1946, 1920-1939, 1920-1947, 1921-1948, 1922-1949, 1923-1950, 1924-1951, 1925-1952, 1926-1952, 1927-1952, 1928-1955, 1962-2059, 2040-2126, 2100-2126, 2100-2139, 2100-2206, 2101-2126, 2305-2332, 2305-2354, 2306-2333, 2307-2334, 2308-2334, 2309-2334, 2310-2334, 2410-2434, 2504-2528, 2509-2528, 2582-2625, 2606-2668, 2828-2855, 2832-2851, 2900-2927, 2900-2929, 2902-2927, 2983-3007, 2983-3013, 3227-3252, 3227-3456, 3472-3496, 또는 3543-3569의 동일 길이 부분에 상보적인 적어도 8개의 인접한 핵염기들로 이루어진 부분을 포함하는 핵염기 서열을 가진 변형된 올리고뉴클레오타이드를 포함하는 화합물로서, 상기 변형된 올리고뉴클레오타이드의 핵염기 서열은 SEQ ID NO: 1에 적어도 90% 상보적인 화합물.