Agent for preventing or treating muscular disease
A myoregulin inhibitor such as an antisense oligonucleotide against myoregulin or an anti-myoregulin antibody is used as an active ingredient of a prophylactic or therapeutic agent for a muscle disease such as muscular dystrophy, inclusion body myositis, amyotrophic lateral sclerosis, disused muscular atrophy, and sarcopenia.
1 . A method for treating muscular dystrophy, comprising:
administering an effective amount of a myoregulin inhibitor to a subject in need thereof,
wherein the myoregulin inhibitor includes an antisense oligonucleotide consisting of 10 to 50 bases and comprising a nucleobase sequence of at least 8 contiguous bases such that the nucleobase sequence is 100% complementary to an equal length portion of a nucleobase sequence of myoregulin.
2 . The method according to claim 1 , wherein the antisense oligonucleotide is consisting of 15 to 30 bases.
3 . The method according to claim 1 , wherein the nucleobase sequence of myoregulin is SEQ ID NO: 1 or SEQ ID NO: 3.
4 . The method according to claim 1 , wherein the nucleobase sequence of myoregulin is a nucleobase sequence having an identity of 90% or more with SEQ ID NO: 1 or SEQ ID NO: 3.
5 . The method according to claim 1 , wherein the muscular dystrophy is Becker muscular dystrophy.
6 . The method according to claim 1 , wherein the muscular dystrophy is Duchenne muscular dystrophy.
7 . The method according to claim 1 , wherein the muscular dystrophy is sarcoglycanopathy.
8 . The method according to claim 1 , wherein the antisense oligonucleotide is a modified oligonucleotide comprising a 5-methylcytosine.
9 . The method according to claim 1 , wherein the antisense oligonucleotide is a modified oligonucleotide including at least one nucleoside comprising a modified sugar.
10 . The method according to claim 9 , wherein the modified sugar has a bicyclic sugar.
11 . The method according to claim 9 , wherein the modified sugar has a substituted sugar moiety.
12 . The method according to claim 1 , wherein the antisense oligonucleotide is a modified oligonucleotide comprising a modified internucleoside linkage.
13 . The method according to claim 1 , wherein the antisense oligonucleotide is a modified oligonucleotide including at least one nucleoside of
wherein B is a nucleobase, each of R1, R2, R3 and R4 is independently a hydrogen atom or a C1-6 alkyl group, each of R5 and R6 is independently a hydrogen atom, a protecting group of a hydroxyl group, a phosphate group, a phosphorus moiety, or a covalent attachment to a support, m is 1 or 2, and M is a sulfonyl group substituted with a methyl group.
14 . The method according to claim 1 , wherein the myoregulin inhibitor is administered orally to the subject in need thereof.
15 . The method according to claim 1 , wherein the myoregulin inhibitor is administered parenterally to the subject in need thereof.
16 . The method according to claim 1 , wherein the myoregulin inhibitor is administered daily in a range of 0.1 ng to 1000 mg per 1 kg body weight per dose.
17 . The method according to claim 1 , wherein the myoregulin inhibitor is administered daily in a range of 1 ng to 100 mg/kg/week.
18 . The method according to claim 1 , wherein the myoregulin inhibitor is administered in a range of 1 to 10 times per month.
19 . The method according to claim 1 , wherein the subject in need thereof is a patient in need thereof.
20 . The method according to claim 1 , wherein the nucleobase sequence of myoregulin is a nucleobase sequence having an identity of 95% or more with SEQ ID NO: 1 or SEQ ID NO: 3.