Complement antagonists and uses thereof

摘要

Disclosed are antagonists designed to inhibit or block expression of a mammalian complement such as complement component 6 (C6). The invention has a wide range of uses including use in the preparation of a medicament for the enhancement of nerve regeneration following acute or chronic nerve damage in a mammal. Additional applications include use in the treatment of multiple sclerosis either alone or in combination with another drug.

主权项

1. An in vitro or in vivo method of reducing or inhibiting the expression of COMPLEMENT COMPONENT 6 (C6) in a cell or a tissue, comprising the step of contacting said cell or tissue with an antisense oligomer so that expression of the COMPLEMENT COMPONENT 6 (C6) is reduced or inhibited, wherein the oligomer is
(a) between about 10 to 50 nucleotides in length having a contiguous nucleobase sequence with at least 80% sequence identity to a complementary region of a nucleic acid which encodes the COMPLEMENT COMPONENT 6 (C6) sequence represented by SEQ ID NO: 1, or a naturally occurring allelic variant thereof, (b) is targeted to about nucleotides 112-152, 433-473, 546-586, 706-746, or 1015-1055 from the ATG start site of SEQ ID NO: 1 (starting at the “A”), (c) comprises at least one nucleotide analogue, and (c) is capable of reducing the level of C6 mRNA expression in a mammal, and wherein the oligomer is (d) single-stranded, or (e) a gapmer comprising 2 or 3 locked nucleic acid (LNA) monomers at each of the 3′ and 5′ ends of the oligomer.