Double-stranded RNA compounds to CASP2 and uses thereof

A method of treating a human patient suffering from or at risk for developing any one or more of primary open angle glaucoma (POAG), normal-tension glaucoma, primary angle-closure glaucoma (PACG), acute angle-closure glaucoma (AACG), angle-closure glaucoma, primary angle closure (PAC), or acute angle closure (AAC), the method comprising administering to the patient's eye via intravitreal (IVT) injection a double-stranded ribonucleic acid (dsRNA) compound that down-regulates CASP2 expression, wherein the double-stranded RNA compound has the structure:

• (sense strand;
• SEQ ID NO:
• 1)
• 5′ iB - GCCAGAAUGUGGAACUCCU 3′
• (antisense strand;
• SEQ ID NO:
• 2)
• 3′ CGGUCUUACACCUUGAGGA 5′
• wherein each A, C, U, and G is a nucleotide and each consecutive nucleotide is joined to the next nucleotide by a phosphodiester bond;
• wherein each nucleotide is independently an unmodified ribonucleotide, a 2′-O-Methyl sugar modified ribonucleotide, or an L-DNA nucleotide;
• wherein the sense strand comprises, counting from the 5′ terminus, an unmodified ribonucleotide at each of positions 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 19 and a L-deoxycytidine at position 18, and an inverted abasic deoxyribose cap (iB) covalently bound to the 5′ terminus;
• wherein the antisense strand comprises, counting from the 5′ terminus, a 2′-O-Methyl sugar modified ribonucleotide at each of positions 2, 4, 6, 8, 11, 13, 15, 17, and 19 and an unmodified ribonucleotide at each of positions 1, 3, 5, 7, 9, 10, 12, 14, 16, and 18;
• or a pharmaceutically acceptable salt thereof;
• and
• wherein the compound is administered to the patient's eye at a dose of about 1.2 mg to about 3.0 mg per eye.