TREATMENT FOR PULMONARY EDEMA, ACUTE LUNG INJURY, AND VASCULAR PERMEABILITY

ABSTRACT:

Acute lung injury (ALI) is characterized by the development of pulmonary edema (accumulation of protein-rich fluid in the alveoli), which results in impaired gas exchange, arterial hypoxemia, and respiratory failure. Nearly 200,000 cases of ALI occur in the US each year and result in almost 75,000 deaths. ALI can result from many insults to the lungs including ischemia-reperfusion-induced injury following cardiac surgery or lung transplantation, ventilator-induced injury following treatment for respiratory failure, pulmonary infections, or other direct and indirect injuries to the lungs. No effective pharmaceutical therapies for ALI are currently available. However, ALI associated pulmonary edema is believed to be caused primarily by increased vascular permeability in the lungs, which is mediated by the integrin alphaVbeta5 protein. Therefore, modulators of alphaVbeta5 may be useful for the treatment of ALI and pulmonary edema.

Integrin alphaVbeta5 has also been implicated in VEGF-mediated endothelial responses, angiogenesis, and vascular permeability throughout the systemic vasculature, not only limited to the lungs. It has also been shown to mediate the effects of VEGF on neuronal damage following cerebral ischemia.  These findings suggest that alphaVbeta5 modulators may have broader utility for the treatment stroke and other diseases related to vascular permeability

DESCRIPTION:

Researchers at UCSF have developed a monoclonal antibody that recognizes human, mouse, and bovine alphaVbeta5.  Administration of the monoclonal antibody in two animal models of ALI (ventilator-induced lung injury and ischemia-reperfusion-induced lung injury) was able to completely block vascular permeability in both disease models and could represent a potential therapy for ALI and pulmonary edema.  Vascular permeability can be induced by different stimuli and can be mediated by multiple cellular pathways, including VEGF, TGF-beta, and thrombin.  Anti-alphaVbeta5 antibody is able to modulate endothelial permeability mediated by these different proteins and pathways.  Antibody modulation of vascular permeability mediated by alphaVbeta5 shows that targeting this receptor may lead to novel treatments for multiple human diseases.

ADVANTAGES:

• Isolation and characterization of anti-alphaVbeta5 monoclonal antibody suitable for humanization and further development
• AlphaVbeta5 modulation for treatment of pulmonary edema, acute lung injury, and diseases associated with vascular permeability shown in multiple animal models

PUBLICATION AND PATENT APPLICATION:

• Integrin alphavbeta5 regulates lung vascular permeability and pulmonary endothelial barrier function.  Am J Respir Cell Mol Biol. 2007 Mar;36(3):377-86

If you would like to receive further information about this technology and potential licensing opportunities, please contact:

Anson Nomura, Ph.D.
Licensing Officer
(415) 353-4626 phone
(415) 348-1579 fax
anson.nomura@ucsf.edu

Reference: OTM Cases #2004-A37