Compositions Comprising PKC-theta and Methods for Treating or Controlling Ophthalmic Disorders Using Same
Compositions for treating or controlling: (i) an eye condition, disorder, or disease, or (ii) a degeneration of a component of an optic nerve system in a subject, comprise a PKC-θ inhibitor. The compositions can further include an anti-inflammatory or anti-glaucoma medicament. Such a condition or degeneration has an inflammatory component.
1 . A composition comprising at least a PKC-θ inhibitor; wherein said at least a PKC-θ inhibitor is present at a concentration such that the composition is capable of treating or controlling an eye condition, disorder, or disease in a subject, wherein said condition, disorder, or disease has an inflammatory component.
2 . The composition of claim 1 , further comprising an anti-inflammatory medicament.
3 . The composition of claim 1 , wherein said condition, disorder, or disease is selected from the group consisting of diabetic retinopathy (“DR”), wet age-related macular degeneration (“AMD”), dry AMD, diabetic macular edema (“DME”), posterior uveitis, anterior uveitis, intermediate uveitis, panuveitis, corneal inflammatory diseases, non-allergic conjunctivitis, keratoconjunctivitis, endophthalmitis, ocular neurodegeneration, glaucoma, optic neuritis, retinitis pigmentosa, and combinations thereof.
4 . The composition of claim 1 , wherein said at least a PKC-θ inhibitor comprises rottlerin.
5 . The composition of claim 3 , wherein said at least a PKC-θ inhibitor is selected from the group consisting of antibodies to PKC-θ.
6 . The composition of claim 5 , wherein said PKC-θ is human PKC-θ.
7 . The composition of claim 3 , wherein said at least a PKC-θ inhibitor comprises a PKC-θ antisense nucleic acid sequence.
8 . The composition of claim 3 , wherein said at least a PKC-θ inhibitor comprises a PKC-θ siNA, siRNA, dsRNA, miRNA, shRNA, or combination thereof.
9 . The composition of claim 3 , wherein said at least a PKC-θ inhibitor is present in an amount in a range from about 0.0001 to about 10 percent by weight of said composition.
10 . The composition of claim 2 , wherein said anti-inflammatory medicament comprises a material selected from the group consisting of non-steroidal anti-inflammatory drugs, DIGRAs, peroxisome proliferator-activated receptor (“PPAR”) ligands, and combinations thereof.
11 . The composition of claim 1 , further comprising a medicament selected from the group consisting of immunosuppressants, cyclooxygenase-2 inhibitors, DMARDS (disease-modifying anti-rheumatic drugs), anti-cell adhesion molecules, and combinations thereof.
12 . The composition of claim 11 , wherein said immunosuppressants are selected from the group consisting of cyclosporine, tacrolimus, rapamycinazathioprine, 6-mercaptopurine, and combinations thereof.
13 . The composition of claim 1 , wherein the composition has a pH in a range from about 5 to about 8.
14 . A composition comprising: (a) at least a PKC-θ inhibitor; and (b) an additional medicament selected from the group consisting of NSAIDs, DIGRAs, VEGF inhibitors, PPAR ligands, immunosuppressants, cyclooxygenase-2 inhibitors, DMARDS, anti-cell adhesion molecules, and combinations thereof; wherein the composition is capable of treating or controlling: (i) an eye condition, disorder, or disease, or (ii) a degeneration of a component of an optic nerve system; wherein each of said at least a PKC-θ inhibitor and said additional medicament, when present, is present in an amount from about 0.0001 to about 5 percent by weight of said composition; and said composition has a pH of about 5-8.
15 . A composition comprising: (a) at least a PKC-θ inhibitor; and (b) an IOP-lowering; wherein the composition is capable of treating or controlling a degeneration of a component of an optic nerve system; wherein each of said at least a PKC-θ inhibitor and said additional medicament, when present, is present in an amount from about 0.0001 to about 5 percent by weight of said composition; and said composition has a pH of about 5-8.
16 . A method for treating or controlling: (i) an eye condition, disorder, or disease, which has an inflammatory component, or (ii) a degeneration of a component of an optic nerve system in a subject, the method comprising administering to an environment of an affected eye a pharmaceutically effective amount of a composition that comprises at least a PKC-θ inhibitor, wherein said composition is administered at a frequency effective to provide said treating or controlling.
17 . The method of claim 16 , wherein said condition, disorder, or disease is selected from the group consisting of DR, wet AMD, dry AMD, DME, posterior uveitis, anterior uveitis, intermediate uveitis, panuveitis, corneal inflammatory diseases, non-allergic conjunctivitis, keratoconjunctivitis, endophthalmitis, ocular neurodegeneration, glaucoma, optic neuritis, retinitis pigmentosa, and combinations thereof.
18 . The method of claim 17 , wherein said at least a PKC-θ inhibitor comprises an antibody to PKC-θ.
19 . The method of claim 18 , wherein said PKC-θ is human PKC-θ.
20 . The method of claim 17 , wherein said at least a PKC-θ inhibitor comprises a PKC-θ antisense nucleic acid molecule.
21 . The method of claim 17 , wherein said at least a PKC-θ inhibitor comprises a PKC-θ siNA, siRNA, dsRNA, miRNA, shRNA, or combination thereof.
22 . The method of claim 17 , wherein said at least a PKC-θ inhibitor is present in an amount in a range from about 0.0001 to about 10 percent by weight of said composition.
23 . The method of claim 17 , wherein the composition further comprises an additional medicament selected from the group consisting of NSAIDs, DIGRAs, VEGF inhibitors, PPAR ligands, immunosuppressants, cyclooxygenase-2 inhibitors, DMARDS, anti-cell adhesion molecules, and combinations thereof; wherein said additional medicament is present in an amount from about 0.0001 to about 5 weight percent.
24 . A method for treating or controlling a degeneration of a component of an optic nerve system in a subject, the method comprising administering to an environment of an affected eye a pharmaceutically effective amount of a composition that comprises at least a PKC-θ inhibitor and an IOP-lowering medicament, wherein said composition is administered at a frequency effective to provide said treating or controlling.
25 . A method for preparing a composition for treating or controlling: (i) an eye condition, disorder, or disease, or (ii) a degeneration of a component of an optic nerve system in a subject, the method comprising combining at least a PKC-θ inhibitor with a pharmaceutically acceptable carrier; wherein said at least a PKC-θ inhibitor is present at a concentration such that the composition is capable of treating or controlling said condition, disorder, disease, or degeneration in a subject.
26 . The method of claim 25 , further comprising adding a medicament selected from the group consisting of NSAIDs, DIGRAs, VEGF inhibitors, PPAR ligands, immunosuppressants, cyclooxygenase-2 inhibitors, DMARDS, anti-cell adhesion molecules, and combinations thereof to the composition.