Prevention and treatment of inflammatory conditions
Inventors
Assignees
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Publication Number
US-11660309-B2
Publication Date
2023-05-30
Expiration Date
Abstract
The present embodiments relate to methods for the prevention and treatment of inflammatory conditions such as alcoholic liver disease (ALD). More specifically the present embodiments relate to the prevention and treatment of ALD through the administration of an Retinoic Acid Receptor (RAR) agonist. Some embodiments relate to use of tazarotene in the prevention and treatment of alcohol-induced liver injury, alcohol-related liver disease, fatty liver disease, hepatic steatosis, alcoholic hepatitis or alcoholic cirrhosis.
Core Innovation
The invention relates to methods and compositions for inhibiting pro-inflammatory type I NKT cells in a subject. It provides RAR-selective agonists, including all-trans retinoic acid (ATRA), tazarotene, and tazarotenic acid, as the administered agents, where the administered RAR-selective agonist inhibits activation of pro-inflammatory type I NKT cells in the subject.
The invention also relates to methods and compositions for preventing or treating inflammatory liver conditions by modulating innate immunity through control of NKT cell subtypes. Type I NKT cells, including alphaGalCer/CD1d-implicated type I NKT cells, are associated with pathogenic activity such as IFN-gamma production and recruitment of myeloid and NK cells, while type II NKT cells activated by sulfatide are described as protective by inhibiting type I NKT activation and thereby inhibiting IFN-gamma secretion.
A further focus is on inflammatory conditions of fibrosis and alcohol-induced liver injury, including alcoholic liver disease and alcoholic hepatitis. In this context, an RAR-selective agonist is administered in an amount sufficient to inhibit activation of pro-inflammatory type I NKT cells, and the inhibition of activation of these cells is described as treating the inflammatory condition of fibrosis.
Claims Coverage
The independent claims cover two main inventive subjects: administering a RAR-selective agonist to inhibit activation of pro-inflammatory type I NKT cells, and treating an inflammatory condition of fibrosis by administering a RAR-selective agonist sufficient to inhibit activation of pro-inflammatory type I NKT cells. Across the independent claims, the inventive focus is on RAR-selective agonist-mediated inhibition of pro-inflammatory type I NKT activation.
Administering a rAR-selective agonist to inhibit activation of pro-inflammatory type I NKT cells
A method of inhibiting pro-inflammatory type I NKT cells in a subject, comprising administering a RAR-selective agonist, wherein the administered RAR-selective agonist inhibits activation of pro-inflammatory type I NKT cells in the subject.
Treating an inflammatory condition of fibrosis by inhibiting pro-inflammatory type I NKT activation
A method of treating an inflammatory condition of fibrosis in a subject in need thereof, the method comprising administering an amount of RAR-selective agonist sufficient to inhibit activation of pro-inflammatory type I NKT cells to the subject, wherein the fibrosis is associated with an increase in pro-inflammatory type I NKT cells and the administered RAR-selective agonist inhibits activation of pro-inflammatory type I NKT cells in the subject, thereby treating the inflammatory condition of fibrosis.
Taken together, the independent claims require administering a RAR-selective agonist that inhibits activation of pro-inflammatory type I NKT cells, either for inhibiting such activation directly or as the basis for treating fibrosis-associated inflammatory conditions where pro-inflammatory type I NKT cells are increased.
Stated Advantages
Inhibits activation of pro-inflammatory type I NKT cells in a subject.
Treats an inflammatory condition of fibrosis by inhibiting activation of pro-inflammatory type I NKT cells.
Addresses inflammatory liver conditions associated with innate immune modulation through type I versus type II NKT control.
Documented Applications
Preventing or treating inflammatory liver conditions, including alcoholic liver disease and inflammatory conditions associated with fibrosis.
Treating an inflammatory condition of fibrosis in a subject in need thereof where fibrosis is associated with an increase in pro-inflammatory type I NKT cells.
Inhibiting activation of pro-inflammatory type I NKT cells in a subject.
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