Method for the diagnosis and follow up of schizophrenia and other mental and neurodegenerative disorders

Inactive Publication Date: 2005-07-21
YEDA RES & DEV CO LTD
View PDF1 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0023] (iii) evaluating the ratio between the ratios obtained in (ii) for the individual tested for schizophrenia and for the at least one healthy control individual, wherein an increase of above 1.6 fold, preferably 2-4, in the D3 dopamine receptor mRNA and/or a decrease of more than 20%, preferably 20-98%, in the α7 AChR mRNA in the tested individual in comparison to healthy individuals, indicate that said tested individual has a high likelihood of having schizophrenia.
[0024] In order to carry out this assay, blood is obtained from individuals, PBLs are isolated therefrom, and total RNA is isolated from the lymphocytes by standard methods as well known in the art. The mRNA of the total RNA is then reverse-transcribed into cDNA that is used for PCR amplification using primers for the D3 dopamine receptor, for the α7 AChR, and for a control house keeping gene such as β-actin, α-actin, NADH or tub

Problems solved by technology

Notably, most drugs effective in treating schizophrenia exhibit D2 receptor antagonistic activity, and administration of a selective D1-like antagonist has been reported to result in the worsening of symptoms (Karlsson. et al., 1995).
Therefore, such binding assays in lymphocytes may not be suitable for a reliable assay for schizophrenia.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for the diagnosis and follow up of schizophrenia and other mental and neurodegenerative disorders
  • Method for the diagnosis and follow up of schizophrenia and other mental and neurodegenerative disorders
  • Method for the diagnosis and follow up of schizophrenia and other mental and neurodegenerative disorders

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0039] Table 1 summarizes the details (ages, sexes, and diagnoses) of schizophrenic patients and healthy controls from whom blood samples were obtained. RT-PCR was performed on total RNA preparations from these blood samples with primers specific for D3 or D4 dopamine receptor, and β-actin as a control. The specific PCR products were resolved on 2% agarose gels, and their sequences were verified. For each patient, a sex- and optimal age-matched healthy control was used, and the. level of specific dopamine receptor. mRNA was compared between sick and healthy patients. As depicted in FIG. 1 (a and b) for several representative patients, the signals for D3 receptor mRNA were significantly higher in schizophrenic patients than in healthy controls. This increase was found to be specific for the D3 dopamine receptor, because no significant differences in the intensities of D4 receptor bands were detected between schizophrenic patients and healthy controls (FIGS. 1b, 1c).

[0040] Quantifica...

example 2

[0044] Thirty four patients were included in this study, 14 men and 20 women, ranging from 18 to 67 year of age. Of these, 20 were hospitalized schizophrenic patients, and 14 unmedicated patients that were examined during their first hospitalization. 21 healthy controls were studied, 11 nonsmokers and 10 smokers, 8 male and 13 female ranging from 31 to 62 years of age. Table 5 summarizes the details (age, sex and diagnosis) of schizophrenic patients and healthy controls participating in this study.

[0045] RNA was prepared from blood samples and RT-PCR was performed on total RNA, using specific primers for the α7 AChR, and for β-actin as a control. The specific PCR products were resolved on 1.5% agarose gels. As depicted in FIG. 2, the signals for α7 AChR were significantly lower in 3 schizophrenic patients than in 3 healthy controls. Quantification of the intensities of the specific α7 AChR and M-actin bands was performed by densitometry. The results obtained in 28 experiments are s...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
Fractionaaaaaaaaaa
Fractionaaaaaaaaaa
Fractionaaaaaaaaaa
Login to View More

Abstract

A method for the diagnosis and follow up of a mental disorder or of a neurodegenerative disorder in an individual, comprises: (i) measuring mRNA of D3 dopamine receptor and / or of α7 nicotinic acetylcholine receptor (α7 AChR) and of a control gene in peripheral blood lymphocytes (PBLs) of said individual and of at least one healthy control individual; (ii) calculating the ratio between the D3 dopamine receptor mRNA and the control gene mRNA and / or the ratio between α7 AChR mRNA and the control gene mRNA for each individual; and (iii) evaluating the ratio between the ratios obtained in (ii) for the tested individual and for the at least one healthy control individual, wherein an increase in the D3 dopamine receptor mRNA and / or a decrease in the α7 AChR mRNA in the tested individual in comparison to healthy individuals, indicate that said tested individual has a high likelihood of having said mental disorder or neurodegenerative disorder, wherein said increase in the D3 dopamine receptor mRNA and / or decrease in the α7 AChR mRNA in the tested individual is correlated to said mental disorder or neurodegenerative disorder. When the mental disorder is schizophrenia, an increase of above 1.6 fold in the D3 dopamine receptor mRNA and / or a decrease of more than 20% in the α7 AChR mRNA in the tested individual in comparison to healthy individuals, indicate that said tested individual has a high likelihood of having schizophrenia.

Description

FIELD OF THE INVENTION [0001] The present invention relates to methods for the diagnosis and follow-up of schizophrenia and other mental and neurodegenerative disorders, and kits for use in said methods. BACKGROUND OF THE INVENTION [0002] Schizophrenia is a neuropsychiatric disorder afflicting about one percent of the population. It is characterized by delusions, hallucinations, disorders in organizing thoughts logically, and emotional withdrawal. There is a well-known tendency for schizophrenia to run in families. [0003] Although the exact pathogenesis of schizophrenia is still not known precisely, a common belief is that excessive activity at dopaminergic synapses in the brain plays a prominent role. To date, a definitive diagnosis of schizophrenia requires a 6-month duration of symptomatology, and relies on heterogeneous symptoms. Because there is neither an effective biological marker for identifying schizophrenia (Willner, 1997; Hietala and Syvalahti, 1996), nor an accurate and...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C12Q1/68C12Q1/6883
CPCC12Q2600/156C12Q1/6883Y02A90/10
InventorFUCHS, SARAILANI, TALPERL, ORLY
OwnerYEDA RES & DEV CO LTD