Small molecule therapeutics for the treatment of asthma

This technology describes small molecules that selectively target the gamma-aminobutyric acid receptor (GABAAR) to control airway hyperresponsiveness and inflammation related to asthma, with reduced side effects on the central nervous system.

Unmet Need: Safe GABAAR activator for the treatment of asthma

Current treatments for bronchoconstrictive diseases include β-adrenergic agonists, inhaled corticosteroids, and inhaled anti-cholinergics. Therapeutic limitations are especially apparent in medications that promote acute airway smooth muscle relaxation, as β-adrenoceptor agonists and anti-cholinergics remain the only drug classes currently utilized to treat acute airway constriction. Activation of GABAAR has been shown to reduce airway hyperresponsiveness, making it a promising therapeutic target for asthma treatment. So far, a variety of small molecule therapeutics targeting GABAAR have been developed, but are often associated with unwanted central nervous system effects and increased mucus production. As such, there is a need to develop GABAAR activators that have limited central nervous system side effects for the treatment of diseases such as asthma.

The Technology: Compounds for treating asthma with reduced side effects

This technology describes compounds that selectively target GABAAR to control airway hyperresponsiveness and inflammation related to asthma. These compounds are positive allosteric modulators that were designed for enhanced selectivity for the alpha-4 subunit of GABAAR. With this enhanced selectivity, these compounds are able to effectively relax contracted airway smooth muscle with reduced adverse side-effects. As a result, this technology provides an safe and effective treatment option for various bronchoconstrictive diseases.

This technology has been validated in mouse models.

Applications:

• Treatment for asthma
• Treatment for inflammation
• Treatment for bronchoconstrictive diseases

Advantages:

• Targets the GABAAR subtype receptor with greater selectivity and efficacy
• Exhibits no central nerve system side effects
• Has high metabolic stability
• Low toxicity

Lead Inventor:

Charles W. Emala, M.D.

Patent Information:

Patent Status

Related Publications:

• Yocum GT, Gallos G, Zhang Y, Jahan R, Stephen MR, Varagic Z, Puthenkalam R, Ernst M, Cook JM, Emala CW. “Targeting the v-aminobutyric acid A receptor α4 subunit in airway smooth muscle to alleviate bronchoconstriction” Am J Respir Cell Mol Biol. 2016 Apr; 54(4): 546-553.

Tech Ventures Reference:

• IR CU17169

• Licensing Contact: Sara Gusik