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Impulse control disorder biological detection marker (Impulsins) and medical purpose of Impulsins

A technology for detecting markers and disorders, applied in biochemical equipment and methods, microbiological determination/inspection, medical preparations containing active ingredients, etc., can solve problems such as undetermined specific substrate ligands

Inactive Publication Date: 2018-10-12
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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  • Impulse control disorder biological detection marker (Impulsins) and medical purpose of Impulsins
  • Impulse control disorder biological detection marker (Impulsins) and medical purpose of Impulsins
  • Impulse control disorder biological detection marker (Impulsins) and medical purpose of Impulsins

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] 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):

[0026] Experimental subjects: wild-type and ATP13A2 gene mutant C57BL / 6 experimental mice

[0027] 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 both ends of homologous recombination and LoxP - Exon 2 -Exon 3 - FRT- Neo Cassette - FRT – LoxP and both ends for homologous recombination was generated by PCR, and the vector was passed through Electroporation inserted into W9.5 passage 28 embryonic stem (ES) cells obtaine...

Embodiment 2

[0029] 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

[0030] Experimental subjects: wild-type and ATP13A2 gene mutant C57BL / 6 experimental mice.

[0031] 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.

[0032] The results showed that the loss of ATP13A2 function caused the mating impulse control disorder, frequent abnormal impulsivity and mating behavior in mice, especially in young or young male animals. The specific manifestation is that the genetic mutant animals frequently chase, smell, and forcib...

Embodiment 3

[0033] 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):

[0034] Experimental subjects: wild-type and ATP13A2 gene mutant C57BL / 6 experimental mice.

[0035] 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.

[0036] 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 impulse control disorder biological detection marker (Impulsins) and a medical purpose of the Impulsins. The medical purpose belongs to application of an ATP enzyme ATP13A2 to preparation of a behavior and motion abnormality disease biological detection marker. The behavior and motion abnormality is caused by impulse control disorder and dyskinesia; and the amino acid sequence of ATP13A2 is shown as SEQ.No.1. The invention also provides application of sphingomyelin reduction and ceramide increase in blood due to APT enzyme ATP13A2 abnormality to preparation of an impulse control behavior and motion abnormality disease biological detection marker. The invention also provides application of a ceramide similar compound FTY720 or a sphingomyelinase inhibition compoundFluoxetine to preparation of medicine for treating impulse control behavior and motion abnormality diseases. Novel treatment medicine is provided for the behavior and motion abnormality diseases. Thetheoretical basis is provided for the clinic study of the behavior and motion abnormality diseases.

Description

technical field [0001] 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 medical use in the aspect of impulsive control disorder related to abnormal sphingolipids, specifically related to the prevention and treatment of nerve impulse control disorder (impulse control disorder, ICD) and motor ataxia, paralysis and dementia by FTY720 Medical use, especially related to the medicine of FTY720 in impulse control disorder and neurodegenerative diseases of Parkinson's disease (PD), spastic paralysis, neuronal ceroid lipofuscinosis and Kufor-Rakeb dementia use. Background technique [0002] Movement and behavior disorders caused by neurodegenerative diseases have caused great harm to patie...

Claims

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Application Information

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IPC IPC(8): C12Q1/34A61K31/137A61P25/00A61P25/28A61P25/16
CPCA61K31/137A61P25/00A61P25/16A61P25/28C12Q1/34G01N2333/914G01N2800/28G01N2800/2821G01N2800/2835
Inventor 刘俊平
Owner HANGZHOU DUANLI BIOTECH CO LTD
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