“Sweet-P”: Molecule for Targeting Human Glucocorticoid Receptor Beta in Asthma and Cancer

Description:

Project ID: D2016-49

 

Background:

Despite many breakthrough innovations occurring in the $14 billion Asthma market, numerous people are still affected by fatal asthma, and the United States contains the largest population affected by severe asthma. Glucocorticoids (GCs) are the most effective and commonly prescribed anti-inflammatory agents in treating asthma. In humans, GC resistance has been documented by two major mechanisms: loss-of-function mutations in glucocorticoid receptor α (GRα) that binds GCs, or by increased expression of glucocorticoid receptor β (GRβ) that does not bind GCs, which acts as a dominant-negative inhibitor of GRα. Although GRα mutations result in GC resistance that is systemic and severe, these mutations are rare. In contrast, GC resistance based on GRβ is more common and tissue-specific in nature. Fatal asthma has been shown to express extremely high levels of GRβ in both large and small airways of the affected people. Ascending levels of GRβ in asthma patients result in GC resistance that can verge on a complete loss of drug response. These maladies have brought the need for the development of an anti-GRβ molecule that may serve as a new therapeutic for (GRβ) related diseases, especially GC-insensitive asthmatic patients.

 

Inventions Description:

Researchers at the University of Toledo have developed the first (and only) anti-GRβ molecule called Sweet-P that targets the GRβ gene known to cause growth, proliferation, migration, and GC hormonal therapy resistance. Sweet-P was designed as a peptide nucleic acid (PNA), conjugated to the Trans-Activator of Transcription (TAT) protein from HIV (for cellular delivery) to specifically target the 3’ untranslated region (3’ UTR) of human GRβ. Sweet-P functions by specifically binding to the 3’UTR of human GRβ and blocking microRNA-144 (miR-144), which increases expression. Sweet-P does not affect GRα levels but explicitly suppresses GRβ increasing the responsiveness to GCs. Sweet-P serves great for reversing GC-resistant diseases. Sweet-P may also be used as a treatment option for several different carcinomas where GRβ is highly expressed, including bladder, prostate, lung, or glioblastoma, as well as for liquid tumors such as in leukemia. Thus, Sweet-P is beneficial for asthma and cancer therapies.

 

Applications:

Asthma, Bladder cancer, Prostate cancer, Leukemia and other GRβ-related diseases.

 

Advantages:

  • Sweet-P is the only compound that has been shown to regulate GRβ.
  • Sweet-P reverses GC resistance.
  • Reducing GC levels with combination therapy limits GC-induced side effects, such as that observed with the mineralocorticoid receptor.
  • Sweet-P is useful in diseases that GRβ is highly expressed such as leukemia, lupus, fatty liver, and asthma, as well as in liver, brain, bladder, prostate and lung cancers.
  • Sweet-P is ready for commercialization and will not require an expensive and lengthy product development period.

IP Status United States Patent 10457947
 

 

 

Patent Information:
For Information, Contact:
Lokesh Mohan
Licensing Associate
The University of Toledo
419-530-6231
lokeshwar.mohan@utoledo.edu
Inventors:
Terry Hinds
Lucien McBeth
Keywords:
Asthma
Bladder Cancer
Glucocorticoid (GC)
Glucocorticoid Receptor α (GRα)
Glucocorticoid Receptor β (GRβ)
Leukemia
Peptide Nucleic Acid (PNA)
Prostate Cancer
Sweet P