Compositions and Methods Useful for the Treatment and Diagnosis of Inflammatory Bowel Disease

• US 20130225440A1
• Filed: 03/27/2013
• Published: 08/29/2013
• Est. Priority Date: 09/27/2010
• Status: Active Grant

• Current Assignee: Children's Hospital of Philadelphia (Children's Hospital of Philadelphia Foundation)
• Original Assignee: Children's Hospital of Philadelphia (Children's Hospital of Philadelphia Foundation)
• Inventors: Friedman, Joshua R., Zahm, Adam, Thayu, Meena
• Granted Patent: US 9,279,158 B2
• Time in Patent Office: Days
• US Class Current: 506/9
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: C12Q 2600/178 miRNA, siRNA or ncRNA

Abstract

Compositions and methods useful for the diagnosis and treatment of IBD including Crohn'"'"'s disease are disclosed.

Claims

1. A method of determining increased risk of a human subject for developing inflammatory bowel disease (IBD) or increased likelihood of the presence of IBD in a human subject comprising the steps of:

(i) measuring in a sample from the subject the level of at least one differentially expressed miRNA provided in FIG. 1; and

(ii) comparing the level of the at least one miRNA in the sample of step i) to a level present in a control sample and/or internal reference miRNA, wherein an increase in the level of at least one miRNA gene product in the sample relative to the control levels of step ii) is indicative of the subject either having increased risk of developing IBD or increased likelihood of the presence of IBD.

2. The method of claim 1, wherein said increased level of expression is correlated with Crohn'"'"'s disease.

3. The method of claim 1, wherein detecting an increase in an amount of one or more miRNAs comprises

(i) labeling miRNAs from total RNA or from small RNAs isolated from a serum sample from said subject

(ii) hybridizing the labeled miRNAs to miRNA probes on a miRNA microarray

(iii) washing the microarray;

and

(iv) detecting the labeled miRNAs remaining on the microarray.

5. The method of claim 1, wherein said internal reference miRNA is one or both of miR-150 and MiR-342-3p.

6. The method of claim 5, wherein expression levels of all of the miRNAs from FIG. 1 are determined.

7. The method of claim 5, wherein the expression level of miR-140 is determined.

8. The method of claim 5, wherein expression levels of mir-484 are determined.

9. The method of claim 5, wherein expression levels of let7-b are determined.

10. A kit for practicing the method of claim 1, 4 or 5, said kit comprising an internal reference miRNA, at least one of an miRNA from FIG. 1, or oligonucleotide, said miRNA or oligonucleotide optionally being immobilized on a solid support, a physiologically acceptable carrier, instructions for use, a container for serum, an assay substrate, or any combination thereof.

11. The kit of claim 10, said kit wherein said at least one miRNA or oligonucleotide is immobilized to a solid support.

4. A method of determining response to therapy in a human subject having IBD, comprising the steps of:

(i) measuring in a serum sample from the subject the level of at least one differentially expressed miRNA provided in FIG. 1, and administering a therapeutic agent useful for the treatment of IBD to said subject, and

(ii) comparing the level of the at least one miRNA in the sample of step i) to levels present after treatment, wherein an decrease in the level of at least one miRNA gene product in the sample relative to pretreatment levels of step ii) is indicative that said therapeutic agent is useful for the treatment of IBD.