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Targets, methods, and reagents for diagnosis and treatment of schizophrenia

a technology for schizophrenia and reagents, applied in the direction of nervous disorders, drug compositions, peptide/protein ingredients, etc., can solve the problems of difficult identification of specific susceptibility genes in these regions, lack of convincing direct genetic, physiological, or biochemical evidence for association of dopamine receptors or nmda receptors with schizophrenia, and inability to achieve true satisfactory treatmen

Inactive Publication Date: 2011-07-14
THE ROCKEFELLER UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention relates to the identification of targets for the diagnosis and treatment of schizophrenia and related conditions. The invention is based on the discovery of a link between the genetics of calciineurin and schizophrenia. The invention provides methods for diagnosis and treatment of schizophrenia by detecting polymorphisms in genes encoding calciineurin and its interacting molecules. The invention also provides methods for screening for compounds useful in treating schizophrenia and related conditions. The compounds identified through these screens can be used to develop pharmaceutical compositions for the treatment of schizophrenia. The invention also provides reagents and knockout or knockdown mice for use in performing screens for compounds useful in treating schizophrenia. Overall, the invention provides new ways to diagnose and treat schizophrenia and related conditions.

Problems solved by technology

Therefore, the identification of specific susceptibility genes in these regions is challenging.
Despite the appeal of these hypotheses, convincing direct genetic, physiological, or biochemical evidence for association of dopamine receptors or NMDA receptors with schizophrenia has not been obtained.
In addition, although various pharmacological agents for the treatment of schizophrenia exist and are widely used, no truly satisfactory therapy exists.

Method used

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  • Targets, methods, and reagents for diagnosis and treatment of schizophrenia
  • Targets, methods, and reagents for diagnosis and treatment of schizophrenia
  • Targets, methods, and reagents for diagnosis and treatment of schizophrenia

Examples

Experimental program
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example 1

Calcineurin-Deficient Mice Display Abnormalities in Activity and Behavior Suggestive of Schizophrenia

[0250]Materials and Methods

[0251]Animals and experimental design. The generation of forebrain specific calcineurin knockout mice (CN mutants) is detailed elsewhere [36]. All behavioral tests were carried out with male mice that were 11 weeks old at the start of the testing. Mice were individually housed in a room with a 12-hr light / dark cycle (lights on at 7:00 a.m.) with access to food and water ad libitum. Behavioral testing was performed between 9:00 a.m. and 5:00 p.m. All procedures relating to animal care and treatment conformed to MIT and NIH guidelines.

[0252]Motor function tests. Motor coordination and balance were tested with the rotarod test. The rotarod test was performed using an accelerating rotarod (UGO Basile Accelerating Rotarod) and consisted of placing a mouse on a rotating drum (3 cm diameter) and measuring the time each animal was able to maintain its balance on th...

example 2

Locations of Calcineurin Subunit Genes, Calcineurin Binding Protein Genes, and Genes Encoding Proteins that Interact with Calcineurin Activity are Coincident with Schizophrenia Susceptibility Loci

[0278]Materials and Methods

[0279]Gene location analysis. To determine the chromosomal locations of calcineurin subunit and calcineurin associated genes, the map viewer function / site of the human draft sequence (http: / / www.ncbi.nlm.nih.gov / cgi-bin / Entrez / hum_srch?chr=hum_chr.inf&query) was searched with query terms such as “calcineurin”, and the precise chromosomal locations of the genes were retrieved. Terms describing the chromosomal positions of the genes (e.g. chromosome 8 or 8q) were combined with the term “schizophrenia”, and the individual combinations were used to search the Entrez Pubmed data base (http: / / www.ncbi.nlm.nih.gov / Entrez / ) to retrieve publications describing schizophrenia susceptibility loci present on those chromosomes. The chromosomal positions of the schizophrenia loc...

example 3

Sequence Analysis of Genes Encoding Calcineurin Subunits and Proteins Associated with Calcineurin Signaling in Schizophrenia Patients

[0324]Materials and Methods

[0325]Patient samples. The United States and South African patient samples utilized in this study have been previously described [1, 2]. Detailed information about the adult schizophrenic (AS) sample is provided in Sobin, C., Blundell, M. L., Conry, A., Weiller, F., Gavigan, C., Haiman, C. & Karayiorgou, M. (2001) Psychiatry Res. 101, 101-113. The South African sample is part of our ongoing collection of schizophrenia patients of Afrikaner origin and will be described in detail elsewhere (M. K., M. Torrington, C. S., B. R., S. C. H., M. L. B., H. Pretorius, S. Lay, J. A. G., and J. L. R., unpublished work). Probands in both samples met lifetime criteria for Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. (DSM-IV) (American Psychiatric Association. (1994) Diagnostic and Statistical Manual (Am. Psychiatric Assoc....

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Abstract

The present invention provides targets, methods, and reagents for the diagnosis and treatment of schizophrenia and related conditions. The invention provides methods for the diagnosis of schizophrenia and susceptibility to schizophrenia by detection of polymorphisms, mutations, variations, alterations in expression, etc., in calcineurin genes or calcineurin interacting genes, or polymorphisms linked to such genes. The invention provides oligonucleotides, arrays, and antibodies for detection of polymorphisms and variants. The invention provides transgenic mice having alterations in such genes. The invention also provides methods of treating schizophrenia by administering compounds that target these genes. The invention further provides screening methods for identifying such compounds and compounds obtained by performing the screens.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Application No. 60 / 367,944, filed Mar. 26, 2002, and U.S. Provisional Patent Application serial number not yet assigned, entitled “Methods for Diagnosis and Treatment of Schizophrenia and Other Psychiatric Disorders and Related Reagents and Methods of Use Thereof”, filed Mar. 7, 2003, listing as inventors Gerber, Karayiorgou, Miyakawa, and Tonegawa. The contents of these applications are incorporated herein by reference.GOVERNMENT SUPPORT[0002]The United States Government has provided grant support utilized in the development of the present invention. In particular, P50-MH58880, awarded by the National Institute of Health; R01-MH61399, awarded by the National Institute of Health have supported development of this invention. The United States Government may have certain rights in the invention.BACKGROUND[0003]Schizophrenia is a severe psychiatric condition that affects approximately one ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/02A61P25/18C12Q1/68
CPCC12Q1/6883C12Q2600/156C12Q2600/136A61P25/18A61P43/00
Inventor GERBER, DAVID J.KARAYIORGOU, MARIAMIYAKAWA, TSUYOSHITONEGAWA, SUSUMU
Owner THE ROCKEFELLER UNIV
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