Methods for selecting a therapy for a subject suffering from schizophrenia

• US 6,833,243 B2
• Filed: 08/16/2001
• Issued: 12/21/2004
• Est. Priority Date: 05/26/1994
• Status: Expired due to Term

• Current Assignee: Nuvelo, Inc. (Arca Biopharma, Inc.)
• Original Assignee: Nuvelo, Inc. (Arca Biopharma, Inc.)
• Inventors: Rozen, Rima
• Primary Examiner(s): Myers, Carla J.
• Application Number:
  US09/931,795
• Publication Number:
  US 20020198211A1
• Time in Patent Office: 1,223 Days
• Field of Search: 435/6, 536/23.1, 536/23.5, 536/23.7
• US Class Current: 435/6.13
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 9/0026 acting on CH-NH groups of donors (1.5)
• CPC Class Codes: C12N 9/0028 with NAD or NADP as acceptor (1.5.1)
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Y 105/0102 Methylenetetrahydrofolate reductase [NAD(P)H] (1.5.1.20)

Abstract

The invention features methods for diagnosing subjects at risk for or suffering from a disease or disorder, such as a psychosis. Methods are also provided for selecting a preferred therapy for a particular subject or group of subjects.

Claims

1. A method for selecting an efficacious therapy for a subject suffering from a schizophrenia, said method comprising the steps of:

(a) analyzing the MTHFR nucleic acid in a sample obtained from said subject;

(b) determining the presence of a heterozygous C/T mutation at position 677 that decreases MTHFR activity or reduces MTHFR thermal dability MTHF in said subject, wherein the presence of said mutation is indicative of the efficacy of a therapy; and

(c) selecting an efficacious neuroleptic therapy for said subject.

2. The method of claim 1, wherein said nucleic acid with said mutation at position 677 is determined to further comprise an additional mutation selected from the group consisting of:

G/A mutation at position 167, a G/A mutation at position 482, a CIT mutation a position 559, a C/T mutation at position 692, a C/T mutation at position 764, a G/A mutation at position 792+1, a C/T mutation at position 985, a CIT mutation at position 1015, a C/T mutation at position 1081, an A/C mutation at position 1298, and a T/C mutation at position 1317, wherein said additional mutation decreases MTHFR activity or reduces MTHFR thermal stability.

3. The method of claim 2, wherein said nucleic acid with said mutation at position 677 comprises an A/C mutation at position 1298.

4. The method of claim 1, wherein said nucleic acid is determined to comprise at least two MTHFR mutations at a position other than 677 that further decrease MTHFR activity or further reduce MTHFR thermal stability.

5. The method of claim 4, wherein said mutations at a position other than 677 comprise at least one of a G/A mutation at position 167, a G/A mutation at position 482, a CIT mutation a position 559, a CIT mutation at position 692, a C/T mutation at position 764, a G/A mutation at position 792+1, a C/T mutation at position 985, a C/T mutation at position 1015, a C/T mutation at position 1081, an A/C mutation at position 1298, or a T/C mutation at position 1317.

6. The method of claim 5, wherein said mutations at a position other than 677 comprise an A/C mutation at position 1298.

13. The method of claim 1, A further comprising the step of determining the presence of at least one MTHFR mutation at a position other than 677 prior to step (c) wherein said mutation decreases MTHFR activity or reduces MTHFR thermal stability.

15. The method of claim 1, wherein said step (c) further comprises selecting a folic acid therapy.

7. A method for treating a schizophrenia in a subject, said method comprising the steps of:

(a) analyzing the MTHFR nucleic acid in a sample obtained from said subject;

(b) determining the presence of a heterozygous C/T mutation at position 677 that decreases MTHFR activity or reduces MTHFR thermal stability in said subject, wherein the presence of said mutation is predictive of the responsiveness of said schizophrenia to a neuroleptic therapy; and

(c) administering said neuroleptic therapy to said subject.

8. The method of claim 7, wherein said nucleic acid with said mutation at position 677 further comprises a G/A mutation at position 167, a G/A mutation at position 482, a C/T mutation a position 559, a C/T mutation at position 692, a C/T mutation at position 764, a G/A mutation at position 792+1, a C/T mutation at position 985, a C/T mutation at position 1015, a C/T mutation at position 1081, an A/C mutation at position 1298, or a T/C mutation at position 1317, wherein said additional mutation decreases MTHFR activity or reduces MTHFR thermal stability.

9. The method of claim 8, wherein said nucleic acid with said mutation at position 677 comprises an A/C mutation at position 1298.

10. The method of claim 7, wherein said nucleic acid is determined to comprise at least two mutations at a position other than 677 that further decrease MTHFR activity or further reduce MTHFR thermal stability.

11. The method of claim 10, wherein said mutations at a position other than 677 comprise at least one of a G/A mutation at position 167, a G/A mutation at position 482, a C/T mutation a position 559, a C/T mutation at position 692, a C/T mutation at position 764, a G/A mutation at position 792+1, a C/T mutation at position 985, a C/T mutation at position 1015, a C/T mutation at position 1081, an A/C mutation at position 1298, or a TIC mutation at position 1317.

12. The method of claim 11, wherein said mutations at a position other than 677 comprise an A/C mutation at position 1298.

14. The method of claim 7, further comprising determining the presence of at least one MTHFR mutation at a position other than 677 prior to step (c), wherein said additional mutation decreases MTHFR activity or reduces MTHFR thermal stability.

16. The method of claim 7, wherein said step (c) further comprises administering a folic acid therapy.