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Composition of novel immune agonist compound and application of novel immune agonist compound in preparation of drugs for preventing and treating Alzheimer's disease

An agonist and complex technology, applied to the composition of a new immune agonist complex, the application in the preparation of drugs for the prevention and treatment of Alzheimer's disease and other neurodegenerative diseases, and the preparation field, which can solve the problem that the pathological process of TREM2AD is not very clear And other issues

Pending Publication Date: 2022-01-14
HANGZHOU XINGAO BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, how TREM2 participates in and affects the pathological process of AD is still not very clear

Method used

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  • Composition of novel immune agonist compound and application of novel immune agonist compound in preparation of drugs for preventing and treating Alzheimer's disease
  • Composition of novel immune agonist compound and application of novel immune agonist compound in preparation of drugs for preventing and treating Alzheimer's disease
  • Composition of novel immune agonist compound and application of novel immune agonist compound in preparation of drugs for preventing and treating Alzheimer's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1: Preparation of novel immune agonist complexes

[0032] (1) Preparation of immune stimulant

[0033] The immune agonist cyclic dinucleotide 2'3'-cGAMP and its derivatives are synthesized by cyclized cGMP-AMP dinucleotide synthetase under the activation conditions after binding to DNA according to the literature method, with a purity of 98% above (Pingwei Li, et al., Immunity, 2013, 39(6), 1019-1031).

[0034] (2) Preparation of recombinant brain homeostasis regulation fusion protein gH625-Zn7MT3

[0035] All biochemical reagents and kits were purchased from Sigama or Invitrogen unless otherwise specified. Amino acid sequence of gH625-MT3 fusion protein (1-91): HGLASTLTRW AHYNALIRAF GGGMDPETCP CPSGGSCTCADSCKCEGCKC TSCKKSCCSC CPAECEKCAK DCVCKGGEAA EAEAEKSSCC Q

[0036]Expression and purification of gH625-MT3 protein: The gene expression vector plasmid of gH625-MT3 protein was synthesized by Shanghai Biological Gene Co., Ltd. The expression vector plasmid was ...

Embodiment 2

[0045] Example 2: Regulation of novel immune agonist compound on cognitive function of Alzheimer's disease mouse model

[0046] experimental method:

[0047] APP / PS1 transgenic Alzheimer's disease (AD) mice were purchased from Shanghai Southern Model Organism Center, aged 5 months, weighing 22-25 g. Test drug name: novel immune stimulant complex (containing STING agonist cGAMP coupled with brain homeostasis regulatory protein and transmembrane peptide fusion protein Zn7MT3gH625), control drugs: 2'3'-cGAMP and Zn7MT3gH625. Properties: colorless powder. Vehicle: normal saline. Preparation method: Prepare the solution with the required concentration with physiological saline solution before use. The dosages are all: 10mg / kg. Administration method: intraperitoneal injection; administration frequency: once a day for 60 consecutive days.

[0048] Morris water maze device for verifying the cognitive ability of Alzheimer's mice: a circular pool with a diameter of 1m, a height of ...

Embodiment 3

[0055] Example 3: Effects of Novel Immune Agonist Compounds on Brain Amyloid in Alzheimer's Disease Mice

[0056] experimental method:

[0057] Five-month-old APPswe / PSEN1dE9 (APP / PS1) double-transgenic Alzheimer's disease mice and control group C57BL / 6 mice (22-25 g) were purchased from Shanghai Southern Model Organism Center. The mice were raised at about 25°C, in an environment with 12 hours of light and 12 hours of darkness alternately, and provided with free food and drinking water. All experimental operations were carried out in accordance with the national standards for experimental animals.

[0058] Test drug: new immune stimulant complex (containing STING agonist cGAMP coupled with brain homeostasis regulatory protein and transmembrane peptide fusion protein Zn7MT3gH625), control drug: 2'3'-cGAMP, Zn7MT3gH625. Properties: colorless powder. Vehicle: normal saline. Preparation method: Prepare the solution with the required concentration with physiological saline sol...

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Abstract

The invention provides a novel immune agonist compound and application thereof in the prevention or treatment of Alzheimer's disease or other neurodegenerative diseases or for the development of drugs for treating Alzheimer's disease (AD) or other neurodegenerative diseases. The novel immune agonist compound is composed of brain metal ion homeostasis regulatory protein, transmembrane peptide fusion recombinant protein coupled liposome and a natural immune agonist. The novel immune agonist compound can remarkably improve AD brain cognitive dysfunction, regulate and control brain metal ion homeostasis balance, inhibit AD brain amyloid protein deposition, inhibit brain nerve cell apoptosis, reduce brain chronic inflammation and effectively prevent disease progression of Alzheimer's disease. Therefore, the novel immune agonist compound has wide application prospect in development of drugs for preventing and treating Alzheimer's disease or other neurodegenerative diseases.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to the composition and preparation method of a novel immune stimulant compound and its application in the preparation of drugs for preventing and treating Alzheimer's disease and other neurodegenerative diseases. Background technique [0002] Alzheimer's Disease (AD), commonly known as senile dementia, has become one of the most serious diseases in the world. There are few anti-Alzheimer's disease drugs approved by the US FDA and China CFDA, and the drugs treat the symptoms but not the root cause , the curative effect is not significant. Most of the global anti-Alzheimer's disease drugs are still in the clinical stage, mainly acting on nerve signaling pathways and Aβ amyloid plaques. However, there are many patients and the demand for drugs is great. The prevalence of AD among people aged 65 and over reaches 4.8%, and the prevalence rate doubles for every 5 years of...

Claims

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Application Information

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IPC IPC(8): A61K39/39A61K9/127A61K47/42A61P25/28
CPCA61K39/39A61K9/1271A61K47/42A61P25/28A61K2039/55511A61K9/127A61K31/7084A61K38/16
Inventor 谭相石向道凤裴建武
Owner HANGZHOU XINGAO BIOTECH CO LTD
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