US2020101042A1PendingUtilityA1

4-methylumbelliferone treatment for immune modulation

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Assignee: BENAROYA RES INSTITUTE AT VIRGINIA MASONPriority: Aug 12, 2013Filed: May 3, 2019Published: Apr 2, 2020
Est. expiryAug 12, 2033(~7.1 yrs left)· nominal 20-yr term from priority
Inventors:Paul L. BollykyNadine NagyThomas N. WightHedwich F. Kuipers
A61P 43/00A61P 5/14A61P 19/02A61K 31/7048A61P 11/06A61P 37/02A61P 17/04A61P 1/04A61K 31/37A61P 5/00A61P 17/02A61P 17/06A61P 3/10A61P 29/00A61P 17/00A61P 37/00A61P 37/08A61P 25/00A61P 1/18
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Claims

Abstract

Compositions for treating autoimmune, allergic, or atopic disease comprising a compound that inhibits hyaluronan synthesis and a pharmaceutically acceptable carrier are described. In some embodiments, the compound that inhibits hyaluronan synthesis is 4-methylumbelliferone or a metabolite of 4-methylumbelliferone. Methods for treating autoimmune diabetes, multiple sclerosis and/or autoimmune demyelination, including administering to the subject a composition having a compound in an amount effective to inhibit hyaluronan synthesis in a mammalian subject, are also described.

Claims

exact text as granted — not AI-modified
The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows: 
     
         1 . A composition for treating an autoimmune, allergic, or atopic disease comprising (i) a compound that inhibits hyaluronan synthesis, and (ii) a pharmaceutically acceptable carrier. 
     
     
         2 . The composition of  claim 1 , wherein the compound is a UDP-glycosyltransferase inhibitor. 
     
     
         3 . The composition of  claim 2 , wherein the compound is a UDP-glucuronyltransferase inhibitor. 
     
     
         4 . The composition of  claim 3 , wherein the compound is 4-methylumbelliferone. 
     
     
         5 . The composition of  claim 4 , wherein the compound is a metabolite of 4-methylumbelliferone. 
     
     
         6 . The composition of  claim 5 , wherein the compound is 4-methylumbelliferone-glucuronide or a sulfated 4-methylumbelliferone. 
     
     
         7 . The composition of  claim 1 , wherein the compound is effective to induce a regulatory T-cell response. 
     
     
         8 . The composition of  claim 7 , wherein the compound is effective to increase FoxP3+ regulatory T-cells. 
     
     
         9 . The composition of  claim 1 , wherein the autoimmune, allergic, or atopic disease is selected from the group consisting of autoimmune diabetes, multiple sclerosis, Sjögrens disease, autoimmune thyroiditis, Lupus, rheumatoid arthritis, psoriasis, colitis, and asthma. 
     
     
         10 . A method for treating an autoimmune, allergic, or atopic disease in a mammalian subject in need thereof, the method comprising administering to the subject a composition comprising a compound in an amount effective to inhibit hyaluronan synthesis in the mammalian subject. 
     
     
         11 . The method of  claim 10 , wherein the compound is a UDP-glycosyltransferase inhibitor. 
     
     
         12 . The method of  claim 11 , wherein the compound is a UDP-glucuronyltransferase inhibitor. 
     
     
         13 . The method of  claim 12 , wherein the compound is 4-methylumbelliferone. 
     
     
         14 . The method of  claim 13 , wherein the compound is a metabolite of 4-methylumbelliferone. 
     
     
         15 . The method of  claim 14 , wherein the compound is 4-methylumbelliferone-glucuronide or a sulfated 4-methylumbelliferone. 
     
     
         16 . The method of  claim 10 , wherein the compound is effective to induce a regulatory T-cell response. 
     
     
         17 . The method of  claim 16 , wherein the compound is effective to increase FoxP3+ regulatory T-cells. 
     
     
         18 . The method of  claim 10 , wherein the mammalian subject is a human subject. 
     
     
         19 . The method of  claim 18 , wherein the human subject is suffering from, or at risk for developing an autoimmune, allergic, or atopic disease selected from the group consisting of autoimmune diabetes, multiple sclerosis, Sjögrens disease, autoimmune thyroiditis, Lupus, rheumatoid arthritis, psoriasis, colitis, and asthma. 
     
     
         20 . A method for treating insulitis and/or reversing progression of autoimmune diabetes in a mammalian subject suffering from or at risk of developing autoimmune diabetes, the method comprising:
 administering to the mammalian subject a composition comprising a compound in an amount effective to inhibit hyaluronan synthesis in the mammalian subject.   
     
     
         21 . The method of  claim 20 , wherein the compound is a UDP-glycosyltransferase inhibitor or a UDP-glucuronyltransferase inhibitor. 
     
     
         22 . The method of  claim 21 , wherein the compound is 4-methylumbelliferone or a metabolite of 4-methylumbelliferone. 
     
     
         23 . The method of  claim 20 , wherein the mammalian subject is a human subject. 
     
     
         24 . A method for treating multiple sclerosis in a mammalian subject in need thereof, the method comprising administering to the subject a composition comprising a compound in an amount effective to inhibit hyaluronan synthesis in the mammalian subject. 
     
     
         25 . The method of  claim 24 , wherein the compound is a UDP-glycosyltransferase inhibitor or a UDP-glucuronyltransferase inhibitor. 
     
     
         26 . The method of  claim 25 , wherein the compound is 4-methylumbelliferone or a metabolite of 4-methylumbelliferone. 
     
     
         27 . The method of  claim 24 , wherein the mammalian subject is a human subject. 
     
     
         28 . The method of  claim 24 , wherein compound is effective to induce a regulatory T-cell response. 
     
     
         29 . The method of  claim 28  wherein the compound is effective to increase FoxP3+ regulatory T-cells. 
     
     
         30 . A method for treating multiple sclerosis and/or autoimmune demyelination in a mammalian subject suffering from or at risk of developing multiple sclerosis, the method comprising:
 administering to the mammalian subject a composition comprising a compound in an amount effective to inhibit hyaluronan synthesis in the mammalian subject.   
     
     
         31 . The method of  claim 30 , wherein the compound is a UDP-glycosyltransferase inhibitor or a UDP-glucuronyltransferase inhibitor. 
     
     
         32 . The method of  claim 31 , wherein the compound is 4-methylumbelliferone or a metabolite of 4-methylumbelliferone. 
     
     
         33 . The method of  claim 30 , wherein the mammalian subject is a human subject. 
     
     
         34 . The method of  claim 30 , wherein compound is effective to induce a regulatory T-cell response. 
     
     
         35 . The method of  claim 34 , wherein the compound is effective to increase FoxP3+ regulatory T-cells.

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