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Rgs2 genotypes associated with extrapyramidal symptoms induced by antipsychotic medication

a technology of antipsychotic drugs and genotypes, applied in the field of rgs2 genotypes associated with resistance or susceptibility to extrapyramidal symptoms induced by antipsychotic drugs, can solve the problems of patients' dependence, patients' families, and society, and the inability to treat with these new drugs alone, etc., to achieve total relief for all psychotic patients

Inactive Publication Date: 2010-01-28
HADASIT MEDICAL RES SERVICES & DEVMENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0010]The present invention provides methods for assessment of the propensity to develop extrapyramidal symptoms (EPS) or for EPS to worsen during treatment with ant

Problems solved by technology

Psychoses exact a tremendous emotional and economic toll on patients, their families, and society as a whole.
The unpleasant side effects induced by antipsychotics often lead patients to stop using them.
While the side effect profile of these atypical antipsychotics is superior to that of typical agents with regard to EPS, treatment with these new drugs alone does not provide total relief to every psychotic patient.
The aforementioned methods do not meet the requirement to determine susceptibility to EPS before initiation of the antipsychotic treatment.

Method used

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  • Rgs2 genotypes associated with extrapyramidal symptoms induced by antipsychotic medication
  • Rgs2 genotypes associated with extrapyramidal symptoms induced by antipsychotic medication
  • Rgs2 genotypes associated with extrapyramidal symptoms induced by antipsychotic medication

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example 1

Demographic and Clinical Features at Baseline and Drug Treatment: Israel Study Sample

[0100]The first set of genetic associations that we examined was of RGS genes with response to antipsychotic treatment at two weeks. Early responders (ER) at this time point, defined by a change in scores on PANSS that exceeded the median, were compared to non-early responders (N-ER). Patients with treatment emergent or worsening Parkinsonism (PARK+) were compared with patients without treatment emergent or worsening Parkinsonism (PARK−) after two weeks of antipsychotic treatment. ER(N=61) and N-ER(N=60) did not differ in background and demographic features including age, gender, education, age at onset, age at first psychiatric hospitalization, cumulative psychiatric hospitalization, dose of typical antipsychotics and risperidone and other treatment details (Table 2). There was a trend for PANSS total scores to be slightly higher in the ER group (ER=24.5±6.4, N-ER=22.0±7.2; p=0.05). There were no s...

example 2

Association of the RGS SNPs with Development of EPS

[0101]Results are based on the Israel study sample. Samples from 6 of the 121 patients were not available for these analyses for technical reasons. PARK+ patients (N=33), who manifested emergent or worsening Parkinson symptoms, as defined by the SAS, were compared to patients without worsening of EPS or treatment emergent symptoms (PARK−, N=82) The two groups did not differ on background or demographic features including age, gender, education, age at onset, age at first psychiatric hospitalization, cumulative psychiatric hospitalization, dose of typical antipsychotics and risperidone and other treatment details (Table 1).

[0102]Several SNPs in RGS genes were examined. These SNPs are listed in Table 3A. Baseline SAS scores were similar (PARK+=12.2±3.1, PARK−=13.9±4.7). As shown in Table 3B, five SNPs within or flanking the RGS2 gene were significantly associated with emergence or worsening of Parkinson symptoms over two weeks of trea...

example 3

Linkage Disequilibrium and Haplotype Tagging SNPs in RGS2

[0103]Table 4 shows the degree of linkage disequilibrium (LD) between SNPs within and flanking RGS2. D′ values are shown above the diagonal and r2 values below the diagonal. An LD block was identified in RGS2 (according to the confidence interval algorithm of Gabriel et al, (Science 2002; 296:2225-2229), which encompasses rs2179652, rs2746073, rs4606 and rs1819741, in SEQ ID NOS. 2-5. The haplotype tagging SNPs (htSNPs) identified within the block were rs2179652 within SEQ ID NO:2, rs4606 within SEQ ID NO:4 and rs1819741 within SEQ ID NO:5.

TABLE 4Linkage disequilibrium (LD) between SNPs within and flanking RGS2SNP / SEQ ID NO.rs1933695 / 1rs2179652 / 2rs2746073 / 3rs4606 / 4rs1819741 / 5rs1152746 / 6rs1933695 / 11.001.001.001.000.04rs2179652 / 20.131.001.001.000.31rs2746073 / 30.060.340.971.000.25rs4606 / 40.060.310.870.970.39rs1819741 / 50.070.361.000.920.45rs1152746 / 60.000.030.010.010.02

[0104]Haplotype analysis was performed on the three tagging SN...

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Abstract

The present invention identifies genotypes associated with resistance to extrapyramidal symptoms induced by antipsychotic drugs. The present invention further identifies genotypes associated with predisposition to the onset or aggravation of extrapyramidal symptoms induced by antipsychotic drugs and use thereof for assessment of patient populations. Specifically, the present invention relates to particular polymorphisms in the RGS2 gene that are associated with resistance or susceptibility to drug-induced extrapyramidal symptoms.

Description

FIELD OF THE INVENTION[0001]The present invention relates to genotypes associated with resistance or susceptibility to extrapyramidal symptoms induced by antipsychotic drugs and use thereof for assessment of patient populations. In particular, the present invention relates to polymorphisms in the RGS2 gene that are associated with resistance or susceptibility to drug-induced extrapyramidal symptoms.BACKGROUND OF THE INVENTION[0002]Psychoses are serious mental illnesses characterized by defective or lost contact with reality. Psychotic patients may suffer hallucinations and delusions as part of their disease. Psychoses exact a tremendous emotional and economic toll on patients, their families, and society as a whole. While the mechanisms underlying these diverse disease states are poorly understood, there are extensive efforts devoted to the discovery of therapies that may offer new hope for the treatment of psychotic patients.[0003]Typical antipsychotic drugs, also called first gene...

Claims

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Application Information

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IPC IPC(8): C12Q1/68
CPCC12Q1/6883C12Q2600/156C12Q2600/106C12Q2600/172C12Q2600/16
Inventor LERER, BERNARDGREENBAUM, LIOR
Owner HADASIT MEDICAL RES SERVICES & DEVMENT
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