Composition and Methods for the Treatment of Degenerative Retinal Conditions

Abstract

The present invention is directed to compositions and methods for the treatment of degenerative retinal conditions. According to a general aspect, the present invention is directed to inflammatory mediators, preferably components or substrates of the NLRP 3 -inflammasome, for use in the treatment of degenerative retinal conditions involving drusen and anaphylatoxin-induced choroidal-neovascularisation. The invention is also directed to a method for the treatment of degenerative retinal conditions involving drusen and anaphylatoxin-induced choroidal-neovascularisation and to recombinant vectors and recombinant proteins for use in such methods. The present invention also provides a method for determining the risk of developing or monitoring the progression of diseases involving drusen and anaphylatoxin-induced choroidal neo-vascularisation.

1 . A method of treating degenerative retinal conditions involving drusen and anaphylatoxin-induced choroidal-neovascularisation comprising administering inflammatory mediators, components, or substrates of the NLRP3-inflammasome to a subject in need thereof. 
     
     
         2 . The method according to  claim 1  wherein the component of the NLRP3-inflammasome is Interleukin-18 (IL-18). 
     
     
         3 . The method according to  claim 1  wherein the retinal condition is selected from the group consisting of age-related macular degeneration, wet age-related macular degeneration, and dry age-related macular degeneration. 
     
     
         4 . The method according to  claim 1  wherein the component of the NLRP3-inflammasome is delivered systemically to said subject. 
     
     
         5 . The method according to  claim 1  wherein the component of the NLRP3 -inflammasome is delivered locally to said subject. 
     
     
         6 . (canceled) 
     
     
         7 . The method according to  claim 1 , wherein said subject is at risk of developing wet age-related macular degeneration (AMD), and wherein choroidal-neovascularisation (CNV) is controlled said subject. 
     
     
         8 . The method according to  claim 1 , wherein Interleukin-18 (IL-18) is administered to said subject prior to the development in said subject of neo-vascular disease or early-stage neo-vascular disease. 
     
     
         9 . The method according to  claim 1 , wherein said subject is at risk of developing wet age-related macular degeneration (AMD), further comprising controlling, maintaining or stimulating Interleukin-18 (IL-18) expression in said subject. 
     
     
         10 . The method according to  claim 1 , wherein Interleukin-18 (IL-18) is delivered to at least one eye, retina, and/or choroid of said subject. 
     
     
         11 . The method according to  claim 1 , wherein Interleukin-18 (IL-18) is delivered to at least one retina of said subject systemically, by injection and/or by viral mediated delivery. 
     
     
         12 . The method according to  claim 1 , wherein Interleukin-18 (IL-18) is delivered to the at least one retina of said subject by adeno-associated viral (AAV) mediated delivery. 
     
     
         13 . The method according to  claim 1 , wherein IL-18 has a protective effect on choroidal neo-vascularisation (CNV) development. 
     
     
         14 . A recombinant viral gene delivery vector which directs the expression of IL-18 in a form suitable for the treatment of choroidal neo-vascularisation. 
     
     
         15 . The recombinant viral gene delivery vector according to  claim 14  in a form for administration to the eye of a subject at risk of developing age-related macular degeneration, wet age-related macular degeneration and/or dry age-related macular degeneration. 
     
     
         16 . The recombinant viral gene delivery vector according to  claim 14  wherein the vector is in a form suitable for delivery to the eye by intraocular injection, sub-retinal, injection, intra-vitreal injection, retrobulbar injection, subconjunctival injection, and/or subtenon injection. 
     
     
         17 . The recombinant viral gene delivery vector according to  claim 14 , wherein the viral vector is an adeno-associated virus (AAV), adenovirus or lentivirus gene delivery vector. 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . A method for treating a subject affected by or at risk of developing a disease involving drusen and anaphylatoxin-induced choroidal neo-vascularisation, the method comprising:
 a) obtaining the level of circulating IL-18 and/or IL-18 binding protein levels in said subject;   b) comparing said IL-18 and/or IL-18 binding protein levels to a reference, wherein the subject's risk of development or progression of the disease drusen and anaphylatoxin-induced choroidal-neovascularisation is based upon the level of IL-18 levels in comparison to said reference; and   c) administering inflammatory mediators, components, or substrates of the NLRP3-inflammasome to said subject based on said binding protein levels.   
     
     
         22 . The method according to  claim 21  wherein the drusen and anaphylatoxin-induced choroidal neo-vascularisation is selected from wet or dry age-related macular degeneration. 
     
     
         23 . The method according to  claim 5  wherein local delivery is selected from intraocular injection, sub-retinal injection, intra-vitreal injection, retrobulbar injection, subconjunctival injection and/or subtenon injection. 
     
     
         24 . The method according to  claim 1 , wherein Interleukin-18 (IL-18) is delivered to at least one retina of said subject by an adeno-associated virus (AAV) expressing an inducible IL-18.