Double-stranded RNA compounds to CASP2 and uses thereof

1. 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.

2. The method of claim 1 , wherein the treatment comprises multiple administrations of the compound.

3. The method of claim 2 , wherein the IVT injections are administered six times.

4. The method of claim 2 , wherein the multiple administrations occur at regular intervals.

5. The method of claim 2 , wherein the compound is administered as six IVT injections at intervals about one month apart.

6. The method of claim 1 , wherein the pharmaceutically acceptable salt is a sodium salt.

7. The method of claim 1 , wherein the compound is administered to the patient's eye as a liquid composition comprising a pharmaceutically acceptable carrier.

8. The method according to claim 7 , wherein a volume of a single dose IVT injection is between about 20 μl to about 200 μl.

9. The method according to claim 7 , wherein a volume of a single dose IVT injection is between about 50 μl to about 100 μl.