METHODS OF TREATING PSYCHOSIS AND SCHIZOPHRENIA BASED ON POLYMORPHISMS IN THE ERBB4 GENE

• US 20100144781A1
• Filed: 10/29/2009
• Published: 06/10/2010
• Est. Priority Date: 10/29/2008
• Status: Abandoned Application

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Wang, Dai, Fu, Dong-Jing, Li, Qingqin S.
• Application Number:
  US12/608,386
• Publication Number:
  US 20100144781A1
• Time in Patent Office: Days
• US Class Current: 514/300
• CPC Class Codes: A61K 31/4375 the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/16 Primer sets for multiplex assays
• CPC Class Codes: C12Q 2600/172 Haplotypes

Abstract

The present application is directed to the use of genetic polymorphism in the ErbB4 gene to predict whether a patient is likely to respond to psychotic medication Paliperidone. The polymorphism in the ErbB4 gene is also used to predict whether a patient is likely to display placebo effect among patients in need of psychotic treatment. A method of treating patients with antipsychotic medication Paliperidone using the polymorphism in the ErbB4 gene and a kit of are also provided.

Claims

1. A method for predicting likelihood of a patient responding to treatment with an atypical antipsychotic drug selected from the group consisting of Paliperidone, and pharmaceutically acceptable salts and esters thereof, comprising:

a) analyzing nucleotide sequences of two alleles of the ErbB4 gene in said patient;

b) determining a genotype at a polymorphic site in the ErbB4 gene, wherein said polymorphic site is at 201 in SEQ ID NO;

1; and

c) identifying the patient with the genotype of GA or GG as being more likely to respond to the drug, and the patient with the genotype of AA as being less likely to respond to the drug.

2. The method of claim 1, wherein the atypical antipsychotic drug is selected from the group consisting of Paliperidone and Paliperidone Palmitate.

3. The method of claim 1, wherein said nucleotide sequences are determined by the method selected from the group consisting of hybridization, sequencing, primer extension, ligase detection reaction, and cleavage method.

4. The method of claim 3, wherein said nucleotide sequences are determined by ligase detection reaction.

5. The method of claim 3, wherein said nucleotide sequences are determined by hybridization.

6. A method for predicting a patient being less likely to respond to a treatment with an atypical antipsychotic drug selected from the group consisting of Paliperidone, and pharmaceutically acceptable salts and esters thereof, comprising:

a) analyzing nucleotide sequences of two alleles of the ErbB4 gene in said patient;

b) determining a genotype at a polymorphic site in the ErbB4 gene, wherein said polymorphic site is at 201 in SEQ ID NO;

1; and

c) identifying the patient with the genotype of AA as being less likely to respond to the drug.

7. The method of claim 6, wherein the atypical antipsychotic drug is selected from the group consisting of Paliperidone and Paliperidone Palmitate.

8. A method for predicting a patient being more likely to respond to a treatment with an atypical antipsychotic drug selected from the group consisting of Paliperidone, and pharmaceutically acceptable salts and esters thereof, comprising:

a) analyzing nucleotide sequences of two alleles of the ErbB4 gene in said patient;

b) determining a genotype of a polymorphic site in the ErbB4 gene, wherein said polymorphic site is at 201 in SEQ ID NO;

1; and

c) identifying the patient with the genotype of GA or GG as being more likely to respond to the drug.

9. The method of claim 8, wherein the atypical antipsychotic drug is selected from the group consisting of Paliperidone and Paliperidone Palmitate.

12. The method of claim 9, further comprising excluding the subject with the genotype of AA from the clinical study of an antipsychotic medication.

10. A method for predicting whether a patient in need of treatment with antipsychotic drug is likely to display placebo response, comprising:

a) analyzing nucleotide sequences of two alleles of the ErbB4 gene in said patient;

b) determining a genotype at a polymorphic site in the ErbB4 gene, wherein said polymorphic site is at 201 in SEQ ID NO;

1; and

c) identifying the patient with the genotype of AA as being likely to display placebo response.

11. A method for selecting a subject for a clinical study of an antipsychotic medication comprising:

a) analyzing nucleotide sequences of two alleles of the ErbB4 gene in said patient;

b) determining a genotype at a polymorphic site in the ErbB4 gene, wherein the polymorphic site is at 201 in SEQ ID NO;

1; and

c) identifying the subject with the genotype of AA as being likely to display placebo response.

13. A method of treating a patient in need of a psychotic treatment comprising:

a) obtaining a DNA sample from the patient;

b) analyzing nucleotide sequences of the ErbB4 gene in the patient;

c) determining a genotype of a polymorphic site in the ErbB4 gene, wherein the polymorphic site is at 201 in SEQ ID NO;

1; and

d) treating the patient with the genotype of GA or GG with an atypical antipsychotic drug selected from the group consisting of Paliperidone, and pharmaceutically acceptable salts and esters thereof.

14. The method of claim 13, wherein the atypical antipsychotic drug is selected from the group consisting of Paliperidone and Paliperidone Palmitate.

15. A kit for use in determining treatment strategy for a patient with a psychotic disorder comprising:

a) a polynucleotide able to recognize and bind to portion of the ErbB4 gene;

b) a container suitable for containing said polynucleotide and a DNA sample from the d patient wherein the polynucleotide can contact the ErbB4 gene; and

means to detect hybridization of the polynucleotide with the ErbB4 gene.

16. The kit of claim 15, further comprising instructions for use.