CN-121987786-A - Use of DDX6 inhibitors in the preparation of a medicament for the treatment of diseases associated with elevated cholesterol

CN121987786ACN 121987786 ACN121987786 ACN 121987786ACN-121987786-A

Abstract

The application provides application of a DDX6 inhibitor in preparing medicines for treating diseases related to cholesterol rise, and the application can inhibit the function of DDX6 genes in liver parenchymal cells by means of gene knockout, effectively reduce the content of cholesterol in mouse blood and prevent damage to liver tissues. Further, analysis of the effects of DDX6 on the liver using transcriptome sequencing found that DDX6 knockout was likely to function by inhibiting cholesterol synthesis in hepatic parenchymal cells.

Inventors

CHEN WEI
FANG LIANG

Assignees

南方科技大学

Dates

Publication Date: 20260508
Application Date: 20250313

Claims (10)

Use of a ddx6 inhibitor for the manufacture of a medicament for the treatment and/or prevention of a disease associated with elevated cholesterol.
Use of a ddx6 inhibitor in a medicament for the treatment and/or prevention of a disease associated with elevated cholesterol.
3. Use according to claim 1 or 2, wherein the disease associated with elevated cholesterol is selected from familial hypercholesterolemia, non-familial hypercholesterolemia, heart disease, metabolic syndrome, diabetes, coronary heart disease, stroke, cardiovascular disease, alzheimer's disease, peripheral arterial disease, hyperlipidemia and dyslipidemia.
Use of a ddx6 inhibitor for the preparation of a medicament for the treatment and/or prevention of a disease selected from the group consisting of: Familial hypercholesterolemia, non-familial hypercholesterolemia, heart disease, metabolic syndrome, diabetes, coronary heart disease, stroke, cardiovascular disease, alzheimer's disease, peripheral arterial disease, hyperlipidemia, and dyslipidemia.
Use of a ddx6 inhibitor in a medicament for the treatment and/or prophylaxis of a disease selected from the group consisting of: Familial hypercholesterolemia, non-familial hypercholesterolemia, heart disease, metabolic syndrome, diabetes, coronary heart disease, stroke, cardiovascular disease, alzheimer's disease, peripheral arterial disease, hyperlipidemia, and dyslipidemia.
6. The use of any one of claims 1-5, wherein the DDX6 inhibitor is a small molecule compound, a polypeptide, a DDX6 protein comprising an inhibitory nucleic acid molecule that hybridizes to a DDX6 nucleic acid molecule, a gene editor, or a mutation.
7. A pharmaceutical composition for the treatment and/or prevention of a disease associated with elevated cholesterol comprising an inhibitor of DDX 6.
8. The pharmaceutical composition of claim 7, wherein the DDX6 inhibitor is a small molecule compound, a polypeptide, a DDX6 protein comprising an inhibitory nucleic acid molecule that hybridizes to a DDX6 nucleic acid molecule, a gene editor, or a mutation.
9. The pharmaceutical composition of claim 7 or 8, further comprising a carrier for delivering a DDX6 inhibitor.
10. The composition of claim 7, wherein the vector is a viral vector or a lipid nanoparticle.

Description

Use of DDX6 inhibitors in the preparation of a medicament for the treatment of diseases associated with elevated cholesterol Technical Field The application relates to the technical field of biomedicine, in particular to application of a DDX6 inhibitor in preparing a medicament for treating diseases related to cholesterol elevation. Background Cholesterol is a small molecule indispensable to human body, and its metabolic regulation includes four main processes of endogenous synthesis, exogenous uptake, esterification storage and efflux. Although cholesterol is indispensable to the body, excessive cholesterol synthesis or intake may induce hypercholesterolemia, and a range of related metabolic diseases including cardiovascular disease, obesity, fatty liver, diabetes, etc. Through decades of research, scientists have deeply understood molecular mechanisms of cholesterol metabolism regulation, and two important cholesterol-lowering drugs are induced (1) because of key roles of HMG-CoA reductase HMGCR in cholesterol synthesis, inhibitors (statin drugs) of the drugs revolutionarily change treatment strategies of hypercholesterolemia, and (2) PCSK9 can inhibit the removal of cholesterol in blood, and monoclonal antibodies aiming at PCSK9 are used for treating familial hypercholesterolemia patients and statin intolerant patients. Despite the clinical success of statins and PCSK9 inhibitors, there are still numerous patients who are unable to tolerate the side effects of existing drugs or are insensitive to existing therapies, and there is a clinical need to develop new therapeutic approaches to control cholesterol levels. Although cholesterol homeostasis is regulated by a number of processes, and in theory, regulation of any one process is likely to be used to treat hypercholesterolemia, currently there are very limited therapeutic approaches that can be used clinically to reduce cholesterol levels. Disclosure of Invention Based on the above technical problems existing in the prior art, the inventors of the present application have found a new target point that can reduce cholesterol synthesis by knocking out DDX6 gene or inhibiting expression of DDX6 gene. The specific technical scheme of the application is as follows: Use of a ddx6 inhibitor for the manufacture of a medicament for the treatment and/or prevention of a disease associated with elevated cholesterol. Use of a ddx6 inhibitor in a medicament for the treatment and/or prevention of a disease associated with elevated cholesterol. 3. The use according to item 1 or 2, wherein the disease associated with elevated cholesterol is selected from familial hypercholesterolemia, non-familial hypercholesterolemia, heart disease, metabolic syndrome, diabetes, coronary heart disease, stroke, cardiovascular disease, alzheimer's disease, peripheral arterial disease, hyperlipidemia and dyslipidemia. Use of a ddx6 inhibitor for the preparation of a medicament for the treatment and/or prevention of a disease selected from the group consisting of: Familial hypercholesterolemia, non-familial hypercholesterolemia, heart disease, metabolic syndrome, diabetes, coronary heart disease, stroke, cardiovascular disease, alzheimer's disease, peripheral arterial disease, hyperlipidemia, and dyslipidemia. Use of a ddx6 inhibitor in a medicament for the treatment and/or prophylaxis of a disease selected from the group consisting of: Familial hypercholesterolemia, non-familial hypercholesterolemia, heart disease, metabolic syndrome, diabetes, coronary heart disease, stroke, cardiovascular disease, alzheimer's disease, peripheral arterial disease, hyperlipidemia, and dyslipidemia. 6. The use of any one of claims 1-5, wherein the DDX6 inhibitor is a small molecule compound, a polypeptide, a DDX6 protein comprising an inhibitory nucleic acid molecule that hybridizes to a DDX6 nucleic acid molecule, a gene editor, or a mutation. 7. A pharmaceutical composition for the treatment and/or prevention of a disease associated with elevated cholesterol comprising an inhibitor of DDX 6. 8. The pharmaceutical composition of item 7, wherein the DDX6 inhibitor is a small molecule compound, a polypeptide, a DDX6 protein comprising an inhibitory nucleic acid molecule that hybridizes to a DDX6 nucleic acid molecule, a gene editor, or a mutation. 9. The pharmaceutical composition of item 7 or 8, further comprising a carrier for delivering a DDX6 inhibitor. 10. The composition of item 7, wherein the vector is a viral vector or a lipid nanoparticle. ADVANTAGEOUS EFFECTS OF INVENTION The application can inhibit the function of DDX6 gene in liver parenchymal cells by means of gene knockout, can effectively reduce the content of cholesterol in mouse blood, and can not cause damage to liver tissues. Further, analysis of the effects of DDX6 on the liver using transcriptome sequencing found that DDX6 knockout was likely to function by inhibiting cholesterol synthesis in hepatic parenchymal cells. Further, a metabol