Differential gene expression in schizophrenia
OwnerSabine Bahn, Margaret Ryan +1inventors
InventorsSabine Bahn, Margaret Ryan, Stephen Huffaker
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Abstract
The invention relates to methods of identifying potential therapeutic agents for the prevention, treatment, or amelioration of schizophrenia, to methods of diagnosis of schizophrenia, to methods of identifying patients most likely to respond to a particular therapeutic treatment, to methods for selecting participants in clinical trials, and to methods of prevention, treatment, or amelioration of schizophrenia.
Claims50
A method for identifying a potential therapeutic agent for the prevention, treatment, or amelioration of schizophrenia, which comprises:
- contacting a cell with a candidate therapeutic agent, or administering a candidate therapeutic agent to an organism;
- determining whether expression of any of the following genes is altered in the cell or organism in response to the candidate therapeutic agent:
- PARG;
- OLR1;
- ARPC3;
- DNCLI1;
- PPM1A;
- ATPIF1;
- TIMM17A;
- DNAJA1;
- SST;
- NEUROD6;
- ICAP-1A;
- FLJ23251;
- KCNK1;
- FLJ13611;
- HIRIP5;
- TAC1;
- MAGEH1;
- C13orf12;
- EBNA1BP2;
- DIRAS2;
- MPPE1;
- OAT;
- OAZIN;
- OAZ2;
- ARG2;
- ATP6V1B2;
- ATP6IP2;
- ATP6V1C1;
- ATP5J;
- ATP5G3;
- ATP5L;
- ATP5C1;
- ATP5F1;
- ATP5A1;
- NDUFA5;
- NDUFA6;
- NDUFAB1;
- NDUFB3;
- NDUFB6;
- NDUFB5;
- NDUFB1;
- NDUFS4;
- NDUFA4;
- NDUFC2;
- NDUFB4;
- UQCRH;
- UQCRFS1;
- UQCRC2;
- UQCRB;
- UQCRC2;
- COX7A2;
- COX7B;
- COX5A;
- COX17;
- COX11;
- COX7CP1;
- COX7BP1;
- HCCS;
- SLC25A4;
- VDAC2;
- VDAC1P;
- VDAC3;
- LDHB;
- LDHA;
- IDH3B;
- IDH3A;
- HMGCR;
- GLRX2;
- FBS1;
- WFS1;
- AMT;
- CLN3;
- ACOX1;
- G6PD;
- GCDH;
- COL5A1;
- NY-REN-24;
- TXNL2;
- SOD3;
- BCAT2;
- ALDH4A1;
- PYCR1;
- MT1X;
- MT1L;
- MT1G;
- MT1H;
- MT2A;
- MT1E;
- MT1F;
- DDAH2;
- AMT;
- HMGCL;
- EPHX1;
- and
- identifying the candidate as a potential therapeutic agent if expression of one or more of the genes is altered.
A screening assay to identify a potential therapeutic agent for the prevention, treatment, or amelioration of schizophrenia comprising using any of the following proteins or nucleic acids:
- (i) proteins encoded by the following genes:
- PARG;
- OLR1;
- ARPC3;
- DNCLI1;
- PPM1A;
- ATPIF1;
- TIMM17A;
- DNAJA1;
- SST;
- NEUROD6;
- ICAP-1A;
- FLJ23251;
- KCNK1;
- FLJ13611;
- HIRIP5;
- TAC1;
- MAGEH1;
- C13orf12;
- EBNA1BP2;
- DIRAS2;
- MPPE1;
- OAT;
- OAZIN;
- OAZ2;
- ARG2;
- ATP6V1B2;
- ATP6IP2;
- ATP6V1C1;
- ATP5J;
- ATP5G3;
- ATP5L;
- ATP5C1;
- ATP5F1;
- ATP5A1;
- NDUFA5;
- NDUFA6;
- NDUFAB1;
- NDUFB3;
- NDUFB6;
- NDUFB5;
- NDUFB1;
- NDUFS4;
- NDUFA4;
- NDUFC2;
- NDUFB4;
- UQCRH;
- UQCRFS1;
- UQCRC2;
- UQCRB;
- UQCRC2;
- COX7A2;
- COX7B;
- COX5A;
- COX17;
- COX11;
- COX7CP1;
- COX7BP1;
- HCCS;
- SLC25A4;
- VDAC2;
- VDAC1P;
- VDAC3;
- LDHB;
- LDHA;
- IDH3B;
- IDH3A;
- HMGCR;
- GLRX2;
- FBS1;
- WFS1;
- AMT;
- CLN3;
- ACOX1;
- G6PD;
- GCDH;
- COL5A1;
- NY-REN-24;
- TXNL2;
- SOD3;
- BCAT2;
- ALDH4A1;
- PYCR1;
- MT1X;
- MT1L;
- MT1G;
- MT1H;
- MT2A;
- MT1 E;
- MT1F;
- DDAH2;
- AMT;
- HMGCL;
- EPHX1;
- or ii) nucleic acid encoding any of the proteins of (i) above.
A method of prevention, treatment, or amelioration of schizophrenia which comprises increasing the level or activity of any of the following proteins in the brain (in particular the prefrontal cortex) of a subject in need of such prevention, treatment, or amelioration:
- PARG;
- OLR1;
- ARPC3;
- DNCLI1;
- PPM1A;
- ATPIF1;
- TIMM17A;
- DNAJA1;
- SST;
- NEUROD6;
- ICAP-1A;
- FLJ23251;
- KCNK1;
- FLJ13611;
- HIRIP5;
- TAC1;
- MAGEH1;
- C13orf12;
- EBNA1BP2;
- DIRAS2;
- MPPE1;
- OAT;
- OAZIN;
- OAZ2;
- ARG2;
- ATP6V1B2;
- ATP6IP2;
- ATP6V1C1;
- ATP5J;
- ATP5G3;
- ATP5L;
- ATP5C1;
- ATP5F1;
- ATP5A1;
- NDUFA5;
- NDUFA6;
- NDUFAB1;
- NDUFB3;
- NDUFB6;
- NDUFB5;
- NDUFB1;
- NDUFS4;
- NDUFA4;
- NDUFC2;
- NDUFB4;
- UQCRH;
- UQCRFS1;
- UQCRC2;
- UQCRB;
- UQCRC2;
- COX7A2;
- COX7B;
- COX5A;
- COX17;
- COX11;
- COX7CP1;
- COX7BP1;
- HCCS;
- SLC25A4;
- VDAC2;
- VDAC1P;
- VDAC3;
- LDHB;
- LDHA;
- IDH3B;
- IDH3A;
- HMGCR;
- GLRX2.
A method of prevention, treatment, or amelioration of schizophrenia which comprises reducing the level or activity of any of the following proteins in the brain (in particular the prefrontal cortex) of a subject in need of such prevention, treatment, or amelioration:
- FBS1;
- WFS1;
- AMT;
- CLN3;
- ACOX1;
- G6PD;
- GCDH;
- COL5A1;
- NY-REN-24;
- TXNL2;
- SOD3;
- BCAT2;
- ALDH4A1;
- PYCR1;
- MT1X;
- MT1L;
- MT1G;
- MT1H;
- MT2A;
- MT1E;
- MT1F;
- DDAH2;
- AMT;
- HMGCL;
- EPHX1.
A method of prevention, treatment, or amelioration of schizophrenia which comprises increasing the level or activity of the majority of the following proteins in the brain (in particular the prefrontal cortex) of a subject in need of such prevention, treatment, or amelioration:
- PARG;
- VDAC2;
- OLR1;
- ARPC3;
- UQCRFS1;
- DNCLI1;
- PPM1A;
- ATPIF1;
- GLRX2;
- TIMM17A;
- IDH3B;
- ARG2;
- DNAJA1;
- SST;
- NEUROD6;
- ICAP-1A;
- FLJ23251;
- KCNK1;
- SLC25A4;
- FLJ13611;
- HIRIP5;
- COX7A2;
- COX5A;
- TAC1;
- UQCRH;
- MAGEH1;
- C13orf12;
- EBNA1BP2;
- DIRAS2;
- MPPE1;
- and reducing the level or activity of the majority of the following proteins in the brain (in particular the prefrontal cortex) of the subject:
- FBS1;
- WFS1;
- AMT;
- CLN3;
- ACOX1;
- G6PD;
- GCDH;
- COL5A1;
- NY-REN-24;
- HMGCL;
- TXNL2;
- SOD3;
- BCAT2;
- MT1X.
Dependencies are inferred from the claim text.