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Application of prolyl hydroxylase inhibitor in preparation of medicine for improving symptoms of hepatolenticular degeneration disease

A technology of prolyl hydroxylase and hepatolenticular degeneration, applied in the medical field, can solve problems such as neurodegeneration side effects and poor patient compliance, and achieve the effects of improving exercise capacity, improving liver pathology, and reducing liver copper accumulation

Active Publication Date: 2021-04-09
THE AFFILIATED HOSPITAL OF HANGZHOU NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disease must be detected and treated as early as possible. Existing copper-dispelling drugs can cause severe neurodegenerative side effects and poor patient compliance, which makes the treatment of this disease still have a big bottleneck

Method used

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  • Application of prolyl hydroxylase inhibitor in preparation of medicine for improving symptoms of hepatolenticular degeneration disease
  • Application of prolyl hydroxylase inhibitor in preparation of medicine for improving symptoms of hepatolenticular degeneration disease
  • Application of prolyl hydroxylase inhibitor in preparation of medicine for improving symptoms of hepatolenticular degeneration disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0056] Example CRISPR / Cas9 construction ATP7B - / - Zebrafish strains and phenotype analysis:

[0057] Constructed by CRISPR / Cas9 ATP7B - / - Zebrafish strain: according to ATP7B Gene sequence, design the gRNA target sequence in exon2 (encoding MBD domain), synthesize primers, and use pMD19- gata5 _gRNAscaffold vector was used as template to prepare gRNA in vitro transcription template. gRNA was obtained by in vitro transcription and purification. Cas9 mRNA (300-600pg) and gRNA (200pg) were freshly mixed and then microinjected into single-cell stage zebrafish embryos, with about 200 injections per target. Embryos injected 48 hours later (30 embryos, 5 embryos / tube), the genome was extracted, the target sequence was obtained by PCR, and sequenced. The injected batches of embryos whose sequencing results are bimodal enter the rearing system, and when they are sexually mature (three months), the next-generation embryos are screened to detect effective mutation types.

[0058...

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Abstract

The invention discloses the application of a prolyl hydroxylase inhibitor in the preparation of a drug for improving the symptoms of hepatolenticular degeneration disease. The prolyl hydroxylase inhibitor used in the invention can stabilize HIF‑1α and activate it. Transcriptional activity; the gray scale of the liver was weakened, and the expression of lipid metabolism factors was significantly reduced. H&E staining of the liver showed that prolyl hydroxylase inhibitors can effectively improve liver pathology and reduce liver copper accumulation; Expression of neuronal signaling and factors related to dopaminergic neuronal signaling was improved, and motor performance was improved.

Description

technical field [0001] The invention relates to the field of medical technology, in particular to the application of prolyl hydroxylase inhibitors in the preparation of medicines for improving the symptoms of hepatolenticular degeneration disease. Background technique [0002] Hepatolenticular degeneration (also known as Wilsondisease, OMIM#277900) is due to ATP7B An autosomal recessive metabolic disease caused by genetic mutations. ATP7B Gene mutations can cause excessive accumulation of copper ions in liver cells, and excessive copper ions can also be deposited in the lenticular nucleus, cornea and kidneys, causing damage to corresponding organs. The global incidence of the disease is about 1 / 30,000, the incidence rate of the Asian population is higher than that of the European and American population, and the incidence rate of the Chinese population is about 1 / 17,000. The disease is a common cause of cirrhosis of unknown cause in adolescents. The clinical manifestation...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/472A61K31/221A61P3/00A61P1/16
CPCA61K31/221A61K31/472A61P1/16A61P3/00
Inventor 芈肖肖施军平
Owner THE AFFILIATED HOSPITAL OF HANGZHOU NORMAL UNIV
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