2678

A novel therapeutic strategy for treatment of asthma using nitroxide radicals

Goldstein Sara, HUJI, Faculty of Science, The Institute of Chemistry
Samuni Amram, HUJI, School of Medicine - IMRIC, Microbiology and Molecular Genetics

 

Category

Life Sciences and Biotechnology   

Keywords

Cyclic nitroxide radicals, asthma, respiratory disease

Current development stage

For Pharmaceutical development: TRL4 - PoC&Safety of candidate device or system is demonstrated in a defined lab or animal model

 

Application
Severe and chronic lung disease like allergic asthma, idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are characterized by poor prognosis and limited treatment options. Oxidative stress is implicated as one of the main pathogenic pathways in those disease.

3-carbamoyl-proxyl (3-CP) is a stable cyclic nitroxide radical. Nitroxides are catalytic antioxidants that preferentially detoxify radicals. Their protective effect has been investigated in several models demonstrating anti-inflammatory, radio-protective, anti-mutagenic, age retardant, hypotensive, anticancer and anti-teratogenic activities.

In the present technology the researchers have found for the first time that nitroxides, also show major effect on key parameters in chronic respiratory diseases.

Our innovation
The effect of 3-CP on respiratory diseases was tested in two preclinical models for chronic lung diseases: allergic asthma and IPF.

Allergic asthma is a chronic disease characterized by airway hyper responsiveness (AHR), reversible airflow obstruction, airway inflammation and remodeling.

Idiopathic pulmonary fibrosis (IPF) causes lung scarring (tissues scar and thicken over time), which causes restrictive-ventilatory limitation, hypoxia, dyspnea, and cough.

Both these disease are characterized by rapid increase in incidence and prevalence and unmet clinical need.

3-CP was found to decrease oxidative injury in the airway of mice and effectively suppress allergic inflammation in acute murine models of asthma. Research showed it was most efficient when administered orally.

In mice IFP model, Intranasal and oral delivery of 3-CP attenuated the extent of lung inflammation, reduced the severity of fibrosis, decreased collagen content and TGF-β expression and improved lung compliance in addition to resistance.  Most importantly, the antifibrotic effect was also observed when the drug was administered after onset lung injury.

Recent Publications:
3-Carbamoyl-proxyl nitroxide radicals attenuate bleomycin-induced pulmonary fibrosis in mice

Cyclic nitroxide radicals attenuate inflammation and Hyper-responsiveness in a mouse model of allergic asthma

Opportunity
The small molecule 3-CP is a promising new therapeutic agent for chronic lung diseases which are associated today with significant unmet clinical needs.

 

 

Patent Status

Granted US 10,441,568; China ZL201680030457; Europe 3273956

Contact for more information:

Keren-Or Amar
VP, Business Development, Healthcare
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