Caspase 1 inhibition to overcome glucocorticoid resistance (SJ-13-0039)

St. Jude Reference #SJ-13-0039

Description

Glucocorticoids (GCs) are steroid hormones that regulate multiple physiological processes involved in inflammation, immunity, metabolism and homeostatic functions.  They are the most commonly used anti-inflammatory and immunosuppressive drugs in the treatment of rheumatic and other inflammatory diseases.  While GCs are relatively inexpensive drugs, their many uses and the enormous volume prescribed translates into a total market size that exceeds US$10 billion per year. 

Researchers at St. Jude have discovered a way to determine if patients prescribed glucocorticoids are likely to be resistant to therapy by measuring the promoter methylation status of two genes, CASP1 and its activator, NLRP3. The invention also describes an intervention for reversing GC resistance by combination therapy.  Potential commercial applications include diagnostic testing and pharmaceutical supplementation of glucocorticoids with CASP1 inhibitors and/or screening for new drug discovery and development by screening libraries of CASP1 inhibitors. 

This technology could be used in nearly all the cases GCs are prescribed, and CASP1 inhibitors have the potential to be used with a subset of the market. In addition to GC treatment for rheumatic and inflammatory diseases, a combination therapy could be used with new acute lymphoblastic leukemia cases and many cancer recurrences.

Keywords

Resistance, Glucocorticoid, Hydrocortisone, Prednisone, Dexamethasone, Methylprednisolone, Prednisolone

Granted patents or published applications

Issued US Patent 10,457,946; and pending US patent application published as 2020-0102565-A1

Related scientific references

Steven W Paugh, et al., Nature Genetics  47, 607–614 (04 May 2015), doi:10.1038/ng.3283

Press release about the publication at: Discovery could help reverse glucocorticoid resistance in some young leukemia patients

Licensing opportunities

We are currently seeking a committed partner to help us develop this technology into a diagnostic to determine which patients maybe more likely to be resistant to glucocorticoid based therapy and an therapeutic intervention for reversing this resistance. Contact: chad.riggs@stjude.org

Contact the Office of Technology Licensing (Phone: 901-595-2342, Fax: 901-595-3148) for more information.