Application of ErbB receptor stimulant to preparation of medicament for treating epilepsy

A receptor agonist and epilepsy technology, which is applied in the application field of ErbB receptor agonists in the preparation of drugs for the treatment of epilepsy, and can solve the problems of lack of kinase activity and the like

Inactive Publication Date: 2012-01-25
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among them, ErbB1 and ErbB2 have no ligand binding region, but the intracellular segment has hydrolysis and kinase activity; while ErbB3 can bind NRG1 but does not have kinase activity

Method used

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  • Application of ErbB receptor stimulant to preparation of medicament for treating epilepsy
  • Application of ErbB receptor stimulant to preparation of medicament for treating epilepsy
  • Application of ErbB receptor stimulant to preparation of medicament for treating epilepsy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1: Mice specifically knocking out ErbB4 receptors on PV interneurons are more prone to epilepsy

[0025] (1) Experimental materials:

[0026] Experimental animal: male PV-Cre-ErbB4 LoxP / LoxP Mice (ErbB4 receptor knockout mice) and littermate control ErbB4 LoxP / LoxP Mice (normal mice containing ErbB4 receptors), 18 each, eight weeks old, weighing 24±2 grams, were raised in the same environment, with free intake of food and water; 12 hours of light were given every day. Behavioral experiments were conducted between 12:00 and 14:00.

[0027] ErbB4 receptor-knockout mice were obtained using the widely used Cre-LoxP recombinase system in the world. The system contains two components: ① a 34bp DNA sequence, containing two 13bp inverted repeat sequences and an 8bp core sequence, the sequence is as follows: 5'-ATAACTTCGTATA-ATGTATGC-TATACGAAGTTAT-3'. This 34bp sequence is the site recognized by the recombinase, known as the loxP site; ②Cre recombinase (cyclizationre...

Embodiment 2

[0038] Example 2: Exogenous intraventricular injection of NRG1 can inhibit epileptic seizures

[0039] (1) Experimental materials:

[0040] Experimental animal: male ErbB4 LoxP / LoxP A total of 20 mice, eight weeks old, weighing 24+2 grams, were raised in the same environment, with free intake of food and water; 12 hours of light were given every day. Behavioral experiments were conducted between 12:00 and 14:00.

[0041] Reagents: PTZ, pilocarpine were purchased from Sigma, USA; Isoflurane (isoflurane) was purchased from Hebei Jiupai Pharmaceutical Company;

[0042] Instrument; stereotaxic apparatus, model 512600, manufactured by Stoelting Company in the United States; anesthesia machine.

[0043] (2) Experimental method:

[0044] According to the previous results, it can be hypothesized that drugs stimulating the NRG1-ErbB4 axis may have antiepileptic effects. Continuous isoflurane (2%) inhalation anesthesia, the mice were fixed under the stereotaxic instrument, after th...

Embodiment 3

[0049] Example 3: The expression of ErbB4 receptors in the brains of human epileptic patients decreased

[0050] (1) Experimental materials:

[0051] Human brain tissue: postoperative brain tissue of 5 patients with intractable epilepsy, meeting the following criteria: I characteristic electroencephalogram, epileptic seizures after more than two years of drug treatment, 2 to 3 first-line antiepileptic drugs used and reached blood level. drug concentration. II Epilepsy symptoms in line with the 1981 International Organization Against Epilepsy classification criteria. No progressive foci under the guidance of IIICT or MRI. IV No neurologic disorder other than epilepsy V Preoperative evaluation pertaining to position-related epileptiform discharges.

[0052] The brain tissues of the control group met the following criteria: I had no history of nervous system diseases. II In addition to the trauma, there is no other injury that can cause changes in brain structure or function ...

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Abstract

The invention provides application of an ErbB receptor stimulant to preparation of a medicament for treating epilepsy. The ErbB receptor stimulant has the advantages: the inhibiting effect of the ErbB4 stimulant NRG1 on epilepsy is disclosed, the organism of epilepsy is studied intensively, a research direction for studying a novel effective 'target' and a molecule of an epilepsy inhibiting medicament is provided, and a basis is laid for the screening of a novel medicament for treating brain diseases based on neuronal excitability changes.

Description

(1) Technical field [0001] The invention relates to the application of ErbB receptor agonist in the preparation of medicine for treating epilepsy. (2) Background technology [0002] Epilepsy is a chronic disease in which the sudden abnormal discharge of brain neurons leads to transient brain dysfunction. The prevalence of epilepsy is high, about 10 million patients in China, affecting about 1% of the total population, and the mortality rate of epilepsy is about 20%. It is a great burden to the family and the society. At present, after the existing antiepileptic drug treatment, about 30% of patients still cannot control it. Epilepsy that cannot be controlled by drugs, that is, intractable epilepsy, has a higher mortality rate, up to 50%. Although surgical treatment is often used for epilepsy that cannot be controlled by drugs, only a small proportion of patients are suitable for surgery. Therefore, finding effective and safe therapeutic drugs is one of the important goals ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61P25/08A61K45/00A61K38/18
Inventor 李晓明李可心卢应梅
Owner ZHEJIANG UNIV
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