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Wip1 gene and purpose of its expressed protein in treatment of amyotrophic lateral sclerosis

A technology for lateral sclerosis and muscular atrophy, applied in the field of neurobiology, can solve the problems of lower incidence of neurodegenerative diseases and decreased expression

Active Publication Date: 2019-06-14
HARBIN MEDICAL UNIVERSITY
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Problems solved by technology

[0007] Many epidemiological studies have reported that the incidence of neurodegenerative diseases has decreased in tumor patients. The latest studies have shown that many genes, proteins and signaling pathways in tumors and neurodegenerative diseases show the opposite situation. This has caused us With great interest, the inventors of the present invention found through previous studies that the expression of the proto-oncogene Wip1, which is closely related to tumor growth, was significantly decreased in the anterior horn motor neurons of the spinal cord of ALS SOD1G93A mice, and was closely related to the occurrence and development of ALS. The relationship between proto-oncogene Wip1 and ALS has not been reported yet

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  • Wip1 gene and purpose of its expressed protein in treatment of amyotrophic lateral sclerosis

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Embodiment 1

[0057] 1. Methods and Materials

[0058] 1. Experimental animals and reagents

[0059] 1.1 Experimental animals and cells

[0060] Mice were purchased from Jackson Laboratory, USA. After co-caging, offspring were bred. After genotype detection, 15 transgenic C57BL / 6J hSOD1G93A genotype-positive mice and 15 C57BL / 6J wild mice were collected, half male and half male.

[0061] NSC-34 cell line was purchased from CEDARLANE Company.

[0062] The previous research group has successfully constructed, flow laser sorted and stably passaged the pLenti viral-NSC34 cell line, wtSOD1-NSC34 cell line and hSOD1G93A NSC34 stably transfected cell line, and divided them into four groups, named as the blank control group (Control group). ), empty virus group (pLV group), wild type group (wtSOD1 group), mutant group (mSOD1 group).

[0063] Primary neurons were obtained from fetal mouse cortical neurons and cultured in Neurobasal medium.

[0064] 1.2 Main reagents

[0065]

[0066]

[0...

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Abstract

The invention discloses a wild-type p53-induced protein phosphatase 1 gene (Wip1) and a purpose of its expressed protein in the treatment of amyotrophic lateral sclerosis. The in-vivo experiment demonstrates that the expression of Wip1 in SOD1G93A ALS mice is significantly decreased and is closely related to the occurrence and development of the disease, overexpression of Wip1 gene can be regulated and controlled in neuronal cells through the gene, and the neuronal survival can be survived by inhibiting a DNA damage response mechanism, which can suggest that high expression of the proto-oncogene Wip1 can treat amyotrophic lateral sclerosis. The present invention also discloses the polymer nanoparticles for treating amyotrophic lateral sclerosis by administering motoneurons that target thebrain and spinal cord of a subject. The Wip1 gene provides a novel technical means for the prevention and treatment of amyotrophic lateral sclerosis.

Description

technical field [0001] The invention relates to a gene therapy method for amyotrophic lateral sclerosis, in particular to wild-type p53-inducible phosphatase 1 (Wip1) gene and its expressed protein in the treatment of amyotrophic lateral sclerosis The invention belongs to the field of neurobiology technology. Background technique [0002] Amyotrophic Lateral Sclerosis (ALS), also known as ALS, is a fatal neurodegenerative disease. It mainly involves upper and lower motor neurons, manifests as progressive muscle weakness and atrophy, and the average survival period is 3-5 years. The latest epidemiological statistics show that the prevalence of ALS is about 5 / 100,000 per year. About 20 percent of familial ALS cases are closely related to mutations in the SOD1 gene. Current studies believe that the pathogenesis of ALS is mainly related to RNA metabolism disorder, abnormal protein homeostasis, mitochondrial dysfunction, oxidative stress, excitatory amino acid toxicity, DNA da...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K47/42A61K48/00A61K31/713A61P25/28C07K7/06C07K1/34
Inventor 丰宏林杨悦青
Owner HARBIN MEDICAL UNIVERSITY
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