Inflammasome activation in myelodysplastic syndromes

Patent metadata

Field	Value
Publication number	US-10688077-B2
Application number	US-201615552578-A
Country	US
Kind code	B2
Filing date	Feb 26, 2016
Priority date	Feb 26, 2015
Publication date	Jun 23, 2020
Grant date	Jun 23, 2020

Abstract

Disclosed are methods for treating a meylodysplastic syndrome (MDS) in a subject that involves administering to the subject a therapeutically effective amount of an inflammasome inhibitor. Also disclosed are methods for diagnosing a myelodysplastic syndrome (MDS) in a subject. In some embodiments, the method involves assaying a sample from the subject to detect inflammasome activation, wherein an increase in inflammasome activation in the sample compared to a control is an indication of MDS in the subject. In some embodiments, the method involves assaying a sample from the subject to detect s100A9 protein levels, wherein an increase in s100A9 protein levels in the sample compared to a control is an indication of MDS in the subject. The disclosed methods can further involve treating the subject for MDS if an increase in inflammasome activation and/or s100A9 levels are detected.

First claim

We claim:

1. A method for treating a myelodysplastic syndromes (MDS) in a subject, comprising administering to the subject a therapeutically effective amount of an inflammasome inhibitor, wherein the MDS in the subject is non-del(5q) MDS or del(5q) MDS.

2. The method of claim 1 , wherein the inflammasome inhibitor comprises a NLRP3 inflammasome inhibitor.

3. The method of claim 2 , wherein the inflammasome inhibitor has the following structure:

4. The method of claim 2 , wherein the inflammasome inhibitor is selected from the group consisting of comprises glybenclamide (glyburide), 5-chloro-2-methoxy-N-[2-(4-sulfamoylphenyl)ethyl]benzamide, and isoliquiritigenin.

5. The method of claim 1 , wherein the inflammasome inhibitor comprises a caspase-1 inhibitor or a pan-caspase inhibitor.

6. The method of claim 1 , wherein the MDS in the subject is non-del(5q) MDS.

7. The method of claim 1 , wherein the MDS in the subject is del(5q) MDS.

8. The method of claim 1 , wherein the inflammasome inhibitor comprises an S100A9 inhibitor.

9. The method of claim 8 , wherein the S100A9 inhibitor is an S100A9 high-affinity chimeric (CD33-IgG 1 ) decoy receptor.

10. The method of claim 5 , wherein the caspase-1 inhibitor is a shRNA targeting CASP1.

11. The method of claim 1 , further comprising administering to the subject a therapeutically effective amount of lenalidomide (LEN).

Assignees

• H Lee Moffitt Cancer Ct & Res

Inventors

• Wei Sheng
• List Alan

Classifications

• G01N33/57505

  of the blood, e.g. leukaemia · CPC title

• C12N2310/14

  interfering nucleic acids [NA] · CPC title

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• G01N2800/7095

  Inflammation · CPC title

• G01N2333/4727

  Calcium binding proteins, e.g. calmodulin · CPC title