Therapeutic uses and methods

A method for improving muscle performance such as muscle or limb strength or delaying decline in muscle performance such as muscle or limb strength in a subject with muscular dystrophy, the method comprising periodically administering to the subject a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of an oligonucleotide comprising the structure:

• 5′ - MeCMeUG AGT MeCTG TTT MeUMeCMeC AMeUMeU
• MeCMeU - 3′
• wherein,
• a) each of the 19 internucleotide linkages of the oligonucleotide is an O,O-linked phosphorothioate diester;
• b) the nucleotides at the positions 1 to 3 from the 5′ end are 2′-O-(2-methoxyethyl) modified ribonucleosides;
• c) the nucleotides at the positions 4 to 12 from the 5′ end are 2′-deoxyribonucleosides;
• d) the nucleotides at the positions 13 to 20 from the 5′ end are 2′-O-(2-methoxyethyl) modified ribonucleosides;
• and
• e) all cytosines are 5-methylcytosines (MeC),
• or a pharmaceutically acceptable salt or stereoisomer thereof, for a time and under conditions sufficient to improve muscle performance such as muscle (e.g, limb) strength or delay decline in muscle performance such as muscle (e.g. limb) strength.

A method of treating muscular dystrophy in a subject in need thereof, the method comprising periodically administering to the subject a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of an inhibitory oligonucleotide comprising the structure:

• 5′ - MeCMeUG AGT MeCTG TTT MeUMeCMeC AMeUMeU
• MeCMeU - 3′
• wherein,
• a) each of the 19 internucleotide linkages of the oligonucleotide is an O,O-linked phosphorothioate diester;
• b) the nucleotides at the positions 1 to 3 from the 5′ end are 2′-O-(2-methoxyethyl) modified ribonucleosides;
• c) the nucleotides at the positions 4 to 12 from the 5′ end are 2′-deoxyribonucleosides;
• d) the nucleotides at the positions 13 to 20 from the 5′ end are 2′-O-(2-methoxyethyl) modified ribonucleosides;
• and
• e) all cytosines are 5-methylcytosines (MeC),
• or a pharmaceutically acceptable salt thereof, or stereoisomer thereof, for a time and under conditions sufficient to improve one or more markers, signs or symptoms of muscular dystrophy, or to delay progression of muscular dystrophy in a subject.

A method for improving muscle function such as limb function or delaying decline in muscle function such as limb function in a subject with muscular dystrophy, the method comprising periodically administering to the subject a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of an oligonucleotide comprising the structure:

• 5′ - MeCMeUG AGT MeCTG TTT MeUMeCMeC AMeUMeU
• MeCMeU - 3′
• wherein,
• a) each of the 19 internucleotide linkages of the oligonucleotide is an O,O-linked phosphorothioate diester;
• b) the nucleotides at the positions 1 to 3 from the 5′ end are 2′-O-(2-methoxyethyl) modified ribonucleosides;
• c) the nucleotides at the positions 4 to 12 from the 5′ end are 2′-deoxyribonucleosides;
• d) the nucleotides at the positions 13 to 20 from the 5′ end are 2′-O-(2-methoxyethyl) modified ribonucleosides;
• and
• e) all cytosines are 5-methylcytosines (MeC),
• or a pharmaceutically acceptable salt or stereoisomer thereof, for a time and under conditions sufficient improve muscle function such as limb function in a subject.