Neuronal viability factor and use thereof

Abstract

The present invention concerns a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound selected in the group comprising (i) a polypeptide comprising an amino acid sequence selected in the group comprising the amino acid sequence of the long isoform in Homo sapiens of the RdCVF2 gene (SEQ ID NO: 10), orthologs, derivatives and fragments thereof, (ii) a polynucleotide coding for said polypeptide, (iii) a vector comprising said polynucleotide, and (iv) a host cell genetically engineered expressing said polypeptide; the use of such a composition for the manufacture of a medicament for treating and/or preventing a neurodegenerative disorder in a subject; and a method of testing a subject thought to have or be predisposed to having a neurodegenerative disorder.

1 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound selected in the group consisting of:
 (i) a polypeptide comprising an amino acid sequence selected in the group consisting of the amino acid sequence of the long isoform in  Homo sapiens  of the RdCVF2 gene (SEQ ID NO:10), orthologs, derivatives and fragments thereof;   (ii) a polynucleotide coding for said polypeptide;   (iii) a vector comprising said polynucleotide; and   (iv) a host cell genetically engineered expressing said polypeptide.   
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the derivatives are selected in the group consisting of polypeptides having a percentage of identity of at least 75% with SEQ ID NO. 10 or orthologs thereof. 
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein said fragments refer to polypeptides having a length of at least 25 amino acids. 
     
     
         4 . The pharmaceutical composition according to  claim 1 , wherein the polynucleotide is selected in the group consisting of RNA and DNA. 
     
     
         5 . The pharmaceutical composition according to  claim 4 , wherein said polynucleotide comprises a sequence which encodes the sequence SEQ ID NO. 10. 
     
     
         6 . The pharmaceutical composition according to  claim 1 , wherein the vector is an expression vector selected in the group consisting of plasmids, viral particles and phages. 
     
     
         7 . The pharmaceutical composition according to  claim 1 , wherein the host cell is selected in the group consisting of bacterial cells, fungal cells, insect cells, animal cells, and plant cells. 
     
     
         8 . A method, for treating and/or preventing a neurodegenerative disorder, comprising the administration of an effective amount of a compound selected in the group consisting of:
 (i) a polypeptide comprising an amino acid sequence selected in the group consisting of the amino acid sequence of long isoform in  Homo sapiens  of the RdCVF2 gene (SEQ ID NO:10), orthologs, derivatives and fragments thereof;   (ii) a polynucleotide coding for said polypeptide;   (iii) a vector comprising said polynucleotide; and   (iv) a host cell genetically engineered expressing said polypeptide to a patient in need thereof.   
     
     
         9 . The method according to  claim 8 , wherein the neurodegenerative disorder is a disease associated with the degeneration of neurons selected in the group consisting of degenerative disorders of the central nervous system, degenerative disorders of the photoreceptors, and degenerative disorders of the olfactory neurons. 
     
     
         10 . The method according to  claim 9 , wherein the degenerative disorder of the central nervous system, is selected in the group consisting of Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease/Chorea. 
     
     
         11 . The method according to  claim 9 , wherein the degenerative disorders of the photoreceptors is cone dystrophy. 
     
     
         12 . A method of testing a subject thought to have or be predisposed to having neurodegenerative disorder, which comprises the step of analyzing a biological sample for:
 (i) detecting the presence of mutation in the RdCVF2 gene and/or its associated promoter, and/or   (ii) analyzing the expression of the RdCVF2 gene.   
     
     
         13 . The pharmaceutical composition according to  claim 2 , wherein the derivatives are selected in the group consisting of polypeptides having a percentage of identity of at least 85% with SEQ ID NO. 10 and orthologs thereof. 
     
     
         14 . The pharmaceutical composition according to  claim 3 , wherein said fragments refer to polypeptides having a length of at least 50 amino acids. 
     
     
         15 . (Ne The pharmaceutical composition according to  claim 4 , wherein the polynucleotide is DNA. 
     
     
         16 . A method for treating Alzheimer's Disease comprising the administration of an effective amount of:
 (i) a polynucleotide coding for a polypeptide comprising an amino acid sequence of long isoform in  Homo sapiens  of the RdCVF2 gene and having the sequence forth in SEQ ID NO:10; or   (ii) a vector comprising said polynucleotide.   
     
     
         17 . A method according to  claim 16 , wherein the vector is an expression vector selected in the group consisting of plasmids, viral particles and phages.