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

• US 20090239908A1
• Filed: 06/03/2009
• Published: 09/24/2009
• Est. Priority Date: 12/10/2001
• Status: Active Grant

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Polymeropoulos, Mihael Hristos, Kudaravalli, Sridhar
• Granted Patent: US 8,460,867 B2
• Time in Patent Office: Days
• US Class Current: 514/321
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 2600/158 Expression markers
• CPC Class Codes: G01N 2333/475 Assays involving growth factors
• CPC Class Codes: G01N 2800/302 Schizophrenia
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

This invention relates to the use of the association between the 103 G>A polymorphism in the CNTF gene to determine antipsychotic treatment strategies in patients with psychotic disorders.

Claims

1. A method of treating a psychotic disorder in an individual in need of such treatment comprising:

(a) determining for each of the two copies of the CNTF gene present in the individual the identity of the nucleotide pair at the polymorphic site 103 G>

A in GenBank sequence reference No. X55890 (Version

     1) wherein;

(b) if both nucleotide pairs are not G, then the individual is treated with alternative therapy, the individual is treated with lloperidone in combination with an alternative therapy, or the individual is treated with a higher dose of iloperidone.

2. A method according to claim 1, wherein determining includes use of a kit for the identification of the individual'"'"'s polymorphism pattern at the CNTF polymorphic site at 103 G>

A, the kit comprising a means for determining a genetic polymorphism pattern at the CNTF polymorphic site at 103 G>

A.

3. A method according to claim 1, wherein the method is performed ex vivo.

4. A method of treating a psychotic disorder in an individual in need of such treatment comprising:

(a) assaying for the presence of a CNTF protein in a biological sample of the individual;

(b) wherein, if CNTF protein is found at a normal level, the patient is treated with lloperidone, and (c) if the CNTF protein is found at a below normal level or is not found at all, the individual is treated with an alternative therapy, with lloperidone in combination with an alternative therapy, or with a higher dose of lloperidone.

5. A method of treating a psychotic disorder in an individual in need of such treatment comprising:

(a) detecting a level of mRNA corresponding to the G variant of the CNTF gene at the polymorphic site 103 G>

A in GenBank sequence reference No. X55890 (Version

     1) in a biological sample of the individual;

(b) detecting a level of mRNA corresponding to the A variant of the CNTF gene at the polymorphic site 103 G>

A in GenBank sequence reference No. X55890 (Version

     1) in a biological sample of the individual;

(c) comparing the levels of G-variant and A-variant mRNA detected in (a) and (b) above wherein, if the G-variant mRNA and the A-variant mRNA are detected at approximately the same level or the G-variant mRNA is not detected, the individual is treated with alternative therapy, with lloperidone in combination with an alternative therapy, or with a higher dose of iloperidone.

6. A method according to claim 5, wherein detecting includes use of a kit for the identification of an mRNA expression product of the CNTF gene, the kit comprising a means for determining the mRNA expression product of the CNTF gene.

7. A method for choosing subjects for inclusion in a clinical study of an anti-psychotic medication comprising:

(a) determining for the two copies of the CNTF gene present in the individual, the identity of the nucleotide pair at the polymorphic site 103 G>

A in GenBank sequence reference No. X55890 (Version

     1) wherein, (b) the individual is excluded from the study if both nucleotide pairs are not G.

8. A kit for use in determining a treatment strategy for an individual with a psychotic disorder comprising:

(a) an antibody able to recognize and bind to a polypeptide expression product of the CNTF gene;

(b) a container suitable for containing the antibody and a sample of body fluid from the said individual wherein the antibody can contact the CNTF polypeptide in the body fluid, if it is present, and (c) means to detect a combination of the antibody and the CNTF polypeptide;

(d) instructions for use of kit.

9. A method for determining the responsiveness of an individual with a psychotic disorder to treatment with lloperidone, comprising;

(a) determining, for the two copies of the CNTF gene present in the individual, the identity of a nucleotide pair at the polymorphic site 103 G>

A in GenBank sequence reference No. X55890 (Version

     1); and

(b) assigning the individual to a low responder group if both nucleotide pairs are not G.