Methods for treating multiple sclerosis using antisense oligonucleotides

A method for treating a human subject afflicted with a form of multiple sclerosis (MS) characterized by the presence of active brain lesions detectable by MRI, the method comprising:

• (i) imaging the subject by MRI or obtaining an MRI image of the subject to detect new active brain lesions;
• (ii) following the imaging, administering to the human subject a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an oligonucleotide corresponding to OLIGONUCLEOTIDE I having the structure:
• 5′-MeCMeUG AGT MeCTG TTT MeUMeCMeC
• AMeUMeU MeCMeU-3′(SEQ ID NO. 1)
• wherein
• each of the 19 internucleotide linkages of the oligonucleotide is an O,O-linked phosphorothioate diester;
• the nucleotides at the positions 1 to 3 from the 5′ end are 2′-O-(2-methoxyethyl) modified ribonucleosides;
• the nucleotides at the positions 4 to 12 from the 5′ end are 2′-deoxyribonucleosides;
• the nucleotides at the positions 13 to 20 from the 5′ end are 2′-O-(2-methoxyethyl) modified ribonucleosides;
• and
• all cytosines are 5-methylcytosines (MeC);
• or a pharmaceutically acceptable salt of the oligonucleotide;
• and
• (iii) following the administration, imaging the subject by MRI or obtaining an MRI image of the subject and detecting in the image that the conversion of the detected new active brain lesions from (i) to new hypointense T1-weighted lesions is inhibited,
• whereby the administration of the pharmaceutical composition is in a dose effective to inhibit the conversion of active brain lesions in the subject into hypointense T1-weighted lesions.