University of Pittsburgh researchers have developed a potent formulation to deliver NADPH oxidase inhibitors to target tissues.
Description
Vascular isoforms of NADPH oxidase (NOX1, NOX2, and NOX4) have been implicated in the pathogenesis of cardiovascular and cardiopulmonary diseases such as pulmonary hypertension. Specifically, Nox2 is a super-oxide generating enzyme which forms reactive oxygen species, contributing to atherosclerotic lesion development and determination of the size of myocardial infarctions, and has been identified as a potential target for treating cardiovascular and cardiopulmonary disease via inhibition.
A Nox2 B-loop peptide, Nox2 docking sequence (Nox2ds) has been shown to effectively inhibit NADPH oxidase and attenuate the progression of cardiopulmonary disease. Nox2ds is selective in differentiating the contribution of Nox2 vs. Nox1 and Nox4 NADPH oxidase. In addition, an aerosolized method of delivery overcomes the low oral bioavailability of peptides that have previously limited their use. This novel inhibitor markedly attenuates cardiac hypertrophy in response to severe forms of pulmonary hypertension, demonstrating its potential clinical use in ameliorating cardiopulmonary diseases.
Applications
• Cardiovascular: Right ventricular hypertrophy, stroke
• Pulmonology: Pulmonary hypertension, acute lung injury, ischemia/reperfusion injury in the lung, pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis
• Neurology: Parkinson’s Disease, Alzheimer’s Disease
• Other: Obstructive sleep apnea, emphysema, atherosclerosis, sepsis
Advantages
• Selectively distinguishes between activity of Nox2 vs. Nox1 and Nox4 NADPH oxidase
• Aerosolized delivery enhances bioavailability
• Easily adaptable for clinical use
Invention Readiness
In vivo data
IP Status
https://patents.google.com/patent/US8962570;
https://patents.google.com/patent/US9585933Related Publication(s)
Csányi, G., Cifuentes-Pagano, E., Al Ghouleh, I., Ranayhossaini, D. J., Egaña, L., Lopes, L. R., Jackson, H. M., Kelley, E. E., & Pagano, P. J. (2011). Nox2 B-loop peptide, Nox2ds, specifically inhibits the NADPH oxidase Nox2. Free Radical Biology and Medicine, 51(6), 1116–1125. https://doi.org/10.1016/j.freeradbiomed.2011.04.025
