Disease-Associated Proteins

Abstract

Disclosed are methods and compositions for early diagnosis, monitoring and treatment of an ocular disorder. In particular, the invention relates to a novel protein, that is differentially transcribed and expressed in subjects suffering from retinal dystrophies and the like, such as retinal dystrophy and age-related macular degeneration compared with healthy subjects, antibodies which recognize this protein, and methods for diagnosing such conditions.

1 . An isolated polypeptide consisting of an amino acid sequence selected from the group consisting of the polypeptides set forth in SEQ2, SEQ 4, SEQ 6, SEQ 8, SEQ10, SEQ12, SEQ14, SEQ16 and SEQ18. 
     
     
         2 . An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a polypeptide according to  claim 1 . 
     
     
         3 . An isolated nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of SEQ1, SEQ3, SEQ 5, SEQ 7, SEQ 9, SEQ 11, SEQ 13, SEQ15 and SEQ17. 
     
     
         4 . A host cell comprising an isolated nucleic acid molecule according to  claim 2 . 
     
     
         5 . A vector molecule comprising at least a fragment of an isolated DNA according to  claims 2 . 
     
     
         6 . A vector molecule according to  claim 5  comprising transcriptional control sequences. 
     
     
         7 . An isolated nucleic acid molecule comprising a nucleotide sequence that hybridizes under high stringency conditions to the isolated DNA of  claims 2 . 
     
     
         8 . A host cell comprising a vector molecule according to  claim 5 . 
     
     
         9 . A vertebrate host cell which can be propagated in vitro and which is capable upon growth in culture of producing a polypeptide according to  claim 1 , wherein said cell comprises at least one transcriptional control sequence, wherein said one or more transcriptional control sequences control transcription of DNA encoding a polypeptide according to  claim 1 . 
     
     
         10 . A vertebrate cell according to  claim 9  wherein said one or more transcriptional control DNA sequences are non-human transcriptional control sequences. 
     
     
         11 . A method for the diagnosis of retinal dystrophy in a human which comprises: detecting the decreased transcription of messenger RNA transcribed from the DNA encoding for a RDCVF1 or RDCVF2 polypeptide, in the eye of a human, wherein said decreased transcription is diagnostic of said human's suffering from retinal dystrophy. 
     
     
         12 . A method for the diagnosis of retinal dystrophy in a human which comprises: measuring the amount of an RDCVF1 or RDCVF2 polypeptide or fragments thereof, in rod cells of a human, wherein the presence of an decreased amount of said polypeptide or fragments thereof, relative to the amount of said polypeptide or fragments thereof in normal eye tissue, is diagnostic of said human's suffering from retinal dystrophy. 
     
     
         13 . The method of  claim 12 , wherein said detecting step comprises contacting said tissue with an antibody which specifically binds to an RDCVF1 or RDCVF2 polypeptide, or a fragment thereof and detecting specific binding of said antibody with a polypeptide in said tissue, wherein detection of specific binding to a polypeptide indicates the presence of an RDCVF1 or RDCVF2 polypeptide, or a fragment thereof. 
     
     
         14 . A purified antibody or a fragment thereof which specifically binds to a polypeptide that comprises the amino acid sequence set forth in SEQ2, SEQ 4, SEQ 6, SEQ 8, SEQ10, SEQ12, SEQ14, SEQ16 and SEQ18. 
     
     
         15 . An antibody fragment according to  claim 14  which is an Fab or F(ab′) 2  fragment. 
     
     
         16 . An antibody according to  claim 14  which is a polyclonal antibody. 
     
     
         17 . An antibody according to  claim 14  which is a monoclonal antibody. 
     
     
         18 . A kit for the diagnosis of retinal dystrophy in a human comprising a means for collecting a sample and an antibody according to  claim 14 . 
     
     
         19 . A method for producing RDCVF1 or RDCVF2 polypeptides comprising: culturing a host cell having incorporated therein an expression vector containing recombinant RDCVF1 or RDCVF2 -encoding polynucleotide under conditions sufficient for expression of RDCVF1 or RDCVF2 polypeptides in the host cell, thereby causing the production of an expressed polypeptide; and recovering the polypeptide produced by said cell. 
     
     
         20 . A method for preventing or protecting neuronal cells from degeneration comprising transfecting said cells with a vector comprising a nucleic acid sequence encoding an RDCVF1 or RDCVF2 polypeptide operably linked to a transcription control sequence, and expressing said polypeptide in said cells. 
     
     
         21 . The method of  claim 20  wherein said cells are retinal cells. 
     
     
         22 . The method of  claim 20  wherein the vector is derived from an adenovirus or an adeno-associated virus. 
     
     
         23 . A retinoprotective agent comprising a polypeptide selected from the group of SEQ2, SEQ 4, SEQ 6, SEQ 8, SEQ10, SEQ12, SEQ14, SEQ16 and SEQ18 and, optionally, a pharmaceutically acceptable carrier. 
     
     
         24 . A retinoprotective agent comprising a therapeutically effective amount of a nucleic acid selected from the group of SEQ1, SEQ3, SEQ 5, SEQ 7, SEQ 9, SEQ 11, SEQ13, SEQ15 and SEQ17 and, optionally, a pharmaceutically acceptable carrier. 
     
     
         25 . A pharmaceutical composition comprising a therapeutically effective amount of a polypeptide selected from the group of SEQ2, SEQ 4, SEQ 6,SEQ 8, SEQ10, SEQ12, SEQ14, SEQ16 and SEQ18 and a pharmaceutically acceptable carrier. 
     
     
         26 . A pharmaceutical composition comprising a therapeutically effective amount of a nucleic acid selected from the group of SEQ1, SEQ3, SEQ 5,SEQ 7, SEQ 9, SEQ 11, SEQ13, SEQ15 and SEQ17 and a pharmaceutically acceptable carrier. 
     
     
         27 . A method for the treatment of retinal dystrophy comprising administering a therapeutically effective amount of a polypeptide selected from the group of SEQ2, SEQ 4, SEQ 6, SEQ 8, SEQ10, SEQ12, SEQ14, SEQ16 and SEQ18, and optionally a pharmaceutically acceptable carrier, to a subject in need of said treatment. 
     
     
         28 . A method according to  claim 27  said retinal dystrophy is retinitis pigmentosa, age-related macular degeneration, Bardet-Biedel syndrome, Bassen-kornzweig syndrome, best disease, choroidema, gyrate atrophy, congenital amourosis, refsun syndrome, stargardt disease or Usher syndrome. 
     
     
         29 . Use of a polypeptide selected from the group of SEQ2, SEQ 4, SEQ 6, SEQ 8, SEQ10, SEQ12, SEQ14, SEQ16 and SEQ18 and, optionally, a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of retinal dystrophy. 
     
     
         30 . Use of  claim 29  wherein said retinal dystrophy is retinitis pigmentosa, age-related macular degeneration, Bardet-Biedel syndrome, Bassen-Kornzweig syndrome, Best disease, choroidema, gyrate atrophy, congenital amourosis, Refsun syndrome, Stargardt disease or Usher syndrome.