Lncrnas for therapy and diagnosis of cardiac hypertrophy

Abstract

The present invention relates to a pharmaceutical composition comprising (i) a compound promoting the expression and/or the activity of one or more long non-coding RNAs (lncRNAs) selected from SEQ ID NOs 12, 8 to 11 and 13; and/or (ii) a compound inhibiting the expression and/or the activity of one or more lncRNAs selected from SEQ ID NOs 1 to 7, 27 and 28. The present invention also relates to a compound (i) promoting the expression and/or the activity of one or more lncRNAs selected from SEQ ID NOs 12, 8 to 11 and 13; and/or (ii) inhibiting the expression and/or the activity of one or more lncRNAs selected from SEQ ID NOs 1 to 7, 27 and 28 for use in treating or preventing cardiac hypertrophy.

1 . A pharmaceutical composition comprising
 (i) a compound comprising a nucleic acid sequence (a) which contains at least 12 contiguous nucleotides selected from SEQ ID NOs 12, 8 to 11 and 13 or (b) which contains a nucleotide sequence which is at least 69% identical to one or more long non-coding RNAs (lncRNAs) selected from SEQ ID NOs 12, 8 to 11 and 13; and/or   (ii) a compound comprising a nucleic acid sequence (a) which is complementary to at least 13 contiguous nucleotides selected from SEQ ID NOs 1 to 7, 27 and 28 or (b) which contains a nucleotide sequence which is at least 69% identical to the complementary strand of one or more lncRNAs selected from SEQ ID NOs 1 to 7, 27 and 28.   
     
     
         2 . A pharmaceutical composition of  claim 1  wherein the compound of (i) and/or (ii) treats or prevents cardiac hypertrophy. 
     
     
         3 . The pharmaceutical composition according to  claim 2 , wherein the cardiac hypertrophy is a ventricular hypertrophy. 
     
     
         4 . The pharmaceutical composition according to  claim 1 , wherein the compound as defined in (ii) is
 (a) a nucleic acid sequence which comprises or consists of a nucleotide sequence being complementary to at least 12 continuous nucleotides of a lncRNAs selected from SEQ ID NOs 1 to 7, 27 and 29,   (b) a nucleic acid sequence which comprises or consists of a nucleotide sequence which is at least 69% identical to the complementary strand of one or more lncRNAs selected from SEQ ID NOs 1 to 7, 27 and 28,   (c) a nucleic acid sequence which comprises or consists of a nucleotide sequence according to (a) or (b), wherein U is replaced by T,   (d) an expression vector expressing the nucleic acid sequence as defined in any one of (a) to (c), or   (e) a host comprising the expression vector of (d).   
     
     
         5 . The pharmaceutical composition according to  claim 1 , wherein the compound as defined in (ii) is an aptamer; or a ribozyme. 
     
     
         6 . The pharmaceutical composition according to  claim 1 , wherein the compound as defined in (i) is
 (a) a nucleic acid sequence which comprises or consists of the nucleic acid sequence of one or more lncRNAs selected from SEQ ID NOs 12, 8 to 11 and 13 or an nucleic acid sequence which is at least 69% identical thereto,   (b) an expression vector expressing the nucleic acid sequence as defined in (a), or   (c) a host comprising the expression vector of (b).   
     
     
         7 . (canceled) 
     
     
         8 . A method for determining expression level of selected lncRNAs in a patient, comprising
 (a) detecting the expression level of one or more lncRNAs selected from SEQ ID NOs 12, 1 to 11, 13, 27 and 28 in a sample obtained from said patient, and   (b) comparing said expression level of the one or more lncRNAs with the expression level of these one or more lncRNAs in a sample obtained from healthy subjects.   
     
     
         9 . The method according to  claim 8 , wherein said sample is a blood sample or blood-derived sample. 
     
     
         10 . The method according to  claim 8 , wherein said sample is a heart tissue sample. 
     
     
         11 . The method according to  claim 8 , wherein the detection of the expression level of the one or more lncRNAs comprises
 (a) quantitative PCR, or   (b) a template/RNA amplification method followed by determining the expression level of the one or more lncRNAs using a fluorescence- or luminescence-based quantification method.   
     
     
         12 . The method of according to  claim 8 , wherein the method comprises prior to the detection of the expression level of the long non-coding RNA a pre-amplification step of the RNA within the test patient's sample and/or the control patient's sample. 
     
     
         13 . A kit for use in the method of  claim 8 , said kit comprising means for the detection of the expression level of one or more lncRNAs selected from SEQ ID NOs 12, 1 to 11, 13, 27 and 28, and instructions how to use the kit. 
     
     
         14 . The kit of  claim 13 , wherein the means are primer pairs used for the specific detection of the expression level of one or more lncRNAs selected from SEQ ID NOs 12, 1 to 11, 13, 27 and 28. 
     
     
         15 . The pharmaceutical composition of  claim 1 , wherein the composition comprises a nucleic acid sequence which is complementary to at least 3 lncRNA selected from SEQ ID NOs 1 to 13, 27, and 28. 
     
     
         16 . The pharmaceutical composition of  claim 4 , wherein the expression vector of (d) expressing the nucleic acid sequence as defined in any one of (a) to (c) is under the control of a heart-specific promoter. 
     
     
         17 . The pharmaceutical composition of  claim 6 , wherein the expression vector of (b) expressing the nucleic acid sequence as defined in (a) is under the control of a heart specific promoter. 
     
     
         18 . The method of  claim 11 , wherein said quantitative PCR is quantitative real time PCR. 
     
     
         19 . The pharmaceutical composition of  claim 15 , wherein the composition comprises a compound which is complementary to a sequence of at least 5 lncRNAs selected from SEQ ID NOs 1 to 13, 27 and 28. 
     
     
         20 . The method of  claim 8 , wherein a greater than 2-fold downregulation of one or more lncRNAs selected from SEQ ID NOs 1 to 7, 27 and 28; and/or a greater than 2-fold upregulation of one or more lncRNAs selected from SEQ ID NOs 12, 8 to 11 and 13 is indicative for a cardiac hypertrophy in the patient.