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MIF and application of MIF in prediction of metabolic adverse reactions induced by second-generation antipsychotic drugs

A technology for antipsychotic drugs and metabolic abnormalities, which is applied in biological testing, biochemical equipment and methods, and microbial measurement/inspection, and can solve problems such as metabolic adverse reactions, abnormal glucose metabolism, and restricted drug use

Pending Publication Date: 2019-06-11
SHANGHAI MENTAL HEALTH CENT (SHANGHAI PSYCHOLOGICAL COUNSELLING TRAINING CENT)
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In addition, although the risk of extrapyramidal syndrome (EPS) produced by atypical antipsychotic drugs is much lower than that of typical antipsychotic drugs, they can cause different degrees of metabolic adverse reactions, such as: weight gain, abnormal glucose metabolism, and dyslipidemia , leading to more severe cardiovascular disease
These side effects severely limit the clinical use of the drug
In addition to causing long-

Method used

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  • MIF and application of MIF in prediction of metabolic adverse reactions induced by second-generation antipsychotic drugs
  • MIF and application of MIF in prediction of metabolic adverse reactions induced by second-generation antipsychotic drugs
  • MIF and application of MIF in prediction of metabolic adverse reactions induced by second-generation antipsychotic drugs

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0076] Clinical Sample Evaluation

[0077] The basic information of 56 first-episode drug-naïve patients treated with olanzapine monotherapy is shown in Table 1.

[0078] Although fasting plasma glucose levels did not change, in these subjects ( figure 1 A-1C), body mass index (BMI), insulinemia and triglyceridemia were all significantly increased ( figure 1 D). The insulin resistance (HOMA-IR) score (index of metabolic dysfunction) also increased from a baseline level of 1.5 to 2.5 ( figure 1 E). Notably, in these patients, plasma MIF concentrations increased after olanzapine treatment ( figure 1 F), and these measures are associated with increased hyperinsulinemia ( figure 1 G), hypertriglyceridemia ( figure 1 H) and insulin resistance score ( figure 1 I) related.

Embodiment 2

[0080] Effect of MIF gene variation on olanzapine-induced metabolic side effects

[0081] Patients were classified as low or high expressing based on a-794CATT5 / 5 genotype (CATT 5 / 5, i.e. lowest MIF expression level), or non-794CATT5 / 5 genotype (CATT not 5 / 5, i.e. higher MIF expression) MIF genotype. Compared with the untreated group, the high MIF genotype group (CATT non-5 / 5) showed increased plasma MIF, HOMA-IR score and BMI, as well as increased plasma levels of insulin, triglycerides and decreased HDL ( figure 2 A). In contrast, in patients with CATT 5 / 5, olanzapine treatment did not alter plasma MIF levels, HOMA IR score, BMI, or other measures of metabolism (i.e., insulin, glucose, triglycerides, HDL, and total cholesterol) ( figure 2 B). Thus, these data suggest that MIF gene variants affect the development of olanzapine-induced metabolic side effects.

Embodiment 3

[0083] Effect of MIF gene variation on risperidone-induced metabolic side effects

[0084] After risperidone was administered to C57 / B6J wild-type and Mif- / - mice for four weeks, the glucose and lipid metabolism phenotypes of the mice were detected.

[0085] The result is as image 3 As shown, after risperidone treatment, the body weight and food intake of wild-type mice increased, but Mif- / - mice before and after risperidone treatment had no significant changes ( image 3 A, 3B). In addition, after risperidone treatment, the glucose tolerance of mice increased (statistically significant), while Mif- / - mice before and after risperidone treatment had no significant changes ( image 3 C). The above results indicated that risperidone-induced symptoms of glucose and lipid metabolism disorders were confirmed to be related to MIF in C57 / B6J mice.

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Abstract

The invention provides MIF and application of a detection reagent of MIF. Specifically, the invention provides application of a macrophage migration inhibition factor (MIF) or a detection reagent thereof in preparation of a diagnostic reagent or a diagnostic kit, and the diagnostic reagent or the diagnostic kit is used for judging the risk of metabolic disorder of a schizophrenia patient after theschizophrenia patient is treated by using a second-generation antipsychotic drug. The invention also provides a corresponding detection kit and a detection method.

Description

technical field [0001] The present invention relates to the fields of pharmacology and molecular detection, more specifically to MIF and its application in predicting metabolic adverse reactions induced by second-generation antipsychotic drugs. Background technique [0002] Schizophrenia (SZ) is a severe, highly prevalent, highly relapsing, chronic and disabling mental disease that mostly occurs in young adults, and its lifetime incidence is about 1% of the world's population. Suffering from schizophrenia not only affects the patient's quality of life and family relationships, but also imposes a serious burden on the social economy. The mortality rate of this disease is 2-3 times higher than that of the general population, and the life expectancy is shortened by 10-20 years compared with the general population. About 60% of the observed higher mortality in schizophrenia than in the general population is attributable to physiological comorbidities, especially cardiovascular ...

Claims

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Application Information

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IPC IPC(8): C12Q1/6883G01N33/53
Inventor 崔东红祁大可彭延敏李泽挚粟幼嵩
Owner SHANGHAI MENTAL HEALTH CENT (SHANGHAI PSYCHOLOGICAL COUNSELLING TRAINING CENT)
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