Methods and Compositions for Modulating the WNT-Signaling Pathway as Treatments for Inflammatory Diseases


Reference #: 01371

The University of South Carolina is offering licensing opportunities for IWR1 as an Immunosuppressant and Anti-inflammatory Agent


Posttraumatic Stress Disorder (PTSD) is a psychiatric disorder accompanied by chronic peripheral inflammation. It is currently unclear what triggers inflammation in PTSD. In the present study, we used an RNA-seq screening analysis of Peripheral Blood Mononuclear cells (PBMCs) from healthy control patients and PTSD patients and found that the Wnt signaling pathway was unregulated in PTSD.  Specifically, we found an increased expression of WNT10B in PTSD when compared to controls. Additionally, in vitro activation studies revealed that activated but not naïve PBMCs from control individuals expressed more IFN in the presence of recombinant WNT10B suggesting that Wnt signaling played a crucial role in exacerbating inflammation. Next, we investigated the mechanism of induction of WNT10B and found that increased expression of WNT10B may result from epigenetic modulations such as downregulation of hsamiR-7113-5p which targeted WNT10B. Furthermore, we also observed that WNT10B overexpression was linked to higher expression of H3K4me3 histone modification around the promotor of WNT10B. Additionally, knockdown of histone demethylase specific to H3K4me3, using siRNA, led to increased expression of WNT10B providing conclusive evidence that H3K4me3 indeed controlled WNT10B expression. In summary, our data demonstrate for the first time that the Wnt signaling pathway is upregulated in PBMCs of PTSD patients resulting from epigenetic changes involving microRNA and histone modifications, which in turn may promote the inflammatory phenotype in such cells.  

Invention Description:

Inhibition/downregulation of excessive expression of pro-inflammatory genes like Interferon gamma (IFNG) and Interleukin (IL) 17 is critical in controlling inflammatory response in several autoimmune and inflammatory diseases. We have identified that a previously reported molecule believed to inhibit cellular pathway, can downregulate inflammatory gene expression. Our data clearly indicates that inflammatory genes such as IFNG, IL17, etc., are significantly downregulated by the molecule. Thus, this inhibitor can be used to treat inflammatory and autoimmune diseases.

Potential Applications:

Chronic inflammation is associated with diseases such as inflammatory and autoimmune diseases, cardiovascular and neurodegenerative diseases, cancer, transplantation and graft-versus-host disease, obesity as well as aging. Thus, controlling inflammation is critical to prevent or treat the disease. Our invention will be useful in controlling the excessive expression of inflammatory genes, thereby leading to the prevention and treatment of such diseases.

Advantages and Benefits:

Since IWR1 is a synthetic molecule, its mass production will not be limited. Currently-available drugs for treating autoimmune and inflammatory diseases are expensive and have various side effects and toxicity issues. 

Patent Information:
Title App Type Country Serial No. Patent No. File Date Issued Date Expire Date Patent Status
Methods and Compositions for Modulating the WNT-Signaling Pathway as Treatments for Inflammatory Diseases Utility United States 16/703,329 11,504,397 12/4/2019 11/22/2022   Published
For Information, Contact:
Technology Commercialization
University of South Carolina
Prakash Nagarkatti
Mitzi Nagarkatti
Bam Marpe
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