Application of compound FTY720 to preparation of detection markers for treating behavior abnormality and motion abnormality

A technology of FTY720, abnormal motion, applied in the fields of biochemical equipment and methods, microbial determination/inspection, measurement devices, etc., can solve the problem of undetermined specific substrate ligands and so on

Pending Publication Date: 2020-07-28
HANGZHOU DUANLI BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

ATP13A2 acts as a lysosomal transmembrane ATPase whose corresponding specific substrate ligand has not been identified

Method used

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  • Application of compound FTY720 to preparation of detection markers for treating behavior abnormality and motion abnormality
  • Application of compound FTY720 to preparation of detection markers for treating behavior abnormality and motion abnormality
  • Application of compound FTY720 to preparation of detection markers for treating behavior abnormality and motion abnormality

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1 ATP13A2 mutation and / or decreased sphingomyelin and increased ceramide and lysosomal phosphatidylethanolamine in serum are biomarkers of anxiety, abnormal behavior, and movement, especially impulse control disorders such as hair pulling and skin peeling, papules Markers for Kinson's disease, Kufor-Rakeb dementia, hereditary spastic paraplegia (SPG), and neuronal ceroid lipofuscinosis (NCL):

[0027] Experimental subjects: wild-type and ATP13A2 gene mutant C57BL / 6 experimental mice

[0028] Experimental approach: Systemic or neuron-specific expression of cre recombinase-mediated gene knockout, behavioral and serum lipidomics. From the mouse 129Sv / J genomic DNA sequence, a DNA fragment with two ends of homologous recombination and LoxP-Exon 2-Exon3-FRT-Neo Cassette-FRT–LoxP and two ends used for homologous recombination was generated by PCR, and the vector was passed through electroporation Transfection inserted into W9.5 passage 28 embryonic stem (ES) cells ob...

Embodiment 2

[0030] Example 2 ATP13A2 mutation and / or decreased serum sphingomyelin and increased ceramide and lysosomal phosphatidylethanolamine are markers of mammalian male impulse control abnormalities such as mating hyperactivity and same-sex mating

[0031] Experimental subjects: wild-type and ATP13A2 gene mutant C57BL / 6 experimental mice.

[0032] Experimental method: Systemic or neuron-specific expression of cre recombinase-mediated gene knockout, behavioral and serum lipidomics detection. The behavioral phenotypes of animals are observed through real-time video, statistics at different time periods, and statistical comparison analysis to obtain significant difference conclusions.

[0033] The results showed that the loss of ATP13A2 function caused impaired mating impulse control, frequent abnormal impulses and mating behaviors in mice, especially in young or young male animals. The specific manifestation is that the genetic mutant animals frequently chase, smell, and forcefully m...

Embodiment 3

[0034] Example 3 ATP13A2 deficiency or dysfunction, and / or decreased serum sphingomyelin, increased ceramide and lysosomal phosphatidylethanolamine, are biomarkers of mammalian aging and related neurodegenerative diseases, especially Parkinson's disease, Markers of ataxia, paralysis in Kufor-Rakeb dementia, hereditary spastic paraplegia (SPG), and neuronal ceroid lipofuscinosis (NCL):

[0035] Experimental subjects: wild-type and ATP13A2 gene mutant C57BL / 6 experimental mice.

[0036] Experimental method: Systemic or neuron-specific expression of cre recombinase-mediated gene knockout, behavioral and serum lipidomics detection. The behavioral phenotypes of animals are observed through real-time video, statistics at different time periods, and statistical comparison analysis to obtain significant difference conclusions.

[0037] The results showed that loss of ATP13A2 function caused motor coordination dysfunction and paralysis that gradually aggravated with age in mice, espec...

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Abstract

The invention provides an application of a compound FTY720 to preparation of detection markers for treating behavior abnormality and motion abnormality. The behavior abnormality and the motion abnormality are caused by nerve impulse control disorder and dyskinesia, and the amino acid sequence of ATP13A2 is shown as SEQ.No.1. The invention also provides an application of reduction of sphingomyelinin blood and rise of ceramide caused by ATPase ATP13A2 abnormality to preparation of biological detection markers for impulse control behaviors and motion abnormality diseases. The invention also provides an application of a ceramide similar compound FTY720 or a sphingomyelinase restraining compound Fluoxetine to preparation of medicines for treating impulse control behaviors and motion abnormality diseases. A new treatment medicine is provided for behavior abnormality diseases and motion abnormality diseases, and a theoretical basis is provided for clinical research of the behavior abnormality diseases and motion abnormality diseases.

Description

[0001] This case is a divisional application with the filing date: 2018.5.3, the application number: 2018104165800, and the invention name: biological detection markers for impulse control disorders and the medical use of Impulsins. technical field [0002] The invention belongs to biotechnology, and relates to a marker, in particular to a method for detecting ATPase ATP13A2 gene mutation, abnormal sphingolipids causing nerve impulse control, behavior and movement disorders, and a class of compounds with therapeutic effects called Impulsins, Impulsins -F1 (FTY720) or impulsin-F2 (Fluooxetine) has medicinal uses for sphingolipid abnormality-related impulse control disorders, specifically related to the prevention and treatment of nerve impulse control disorders (impulse control disorder, ICD) and motor ataxia, paralysis and dementia by FTY720 Medical use, especially related to the medicine of FTY720 on impulse control disorder and neurodegenerative diseases of Parkinson's diseas...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/34A61K31/137A61P25/00A61P25/28A61P25/16
CPCA61P25/00A61P25/16A61P25/28A61K31/137C12Q1/34G01N2800/28G01N2800/2821G01N2800/2835G01N2333/914
Inventor 刘俊平
Owner HANGZHOU DUANLI BIOTECH CO LTD
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