Novel Lipid Inhibitors of TLR Effective at Reducing RSV and Influenza A Infection In Vivo

Tech ID: 07-07

Video - POPG, Promising Antiviral

Background

Respiratory Syncytial Virus (RSV) is the most common cause of hospitalization for respiratory illness in young children and 90% of children under the age of 2 will be infected by this virus. RSV infection and associated inflammation have also been shown to be a substantial contributing factor in the exacerbation of chronic lung diseases in adults and the elderly. Influenza A virus (IAV) is a worldwide public health problem causing 500,000 deaths each year with the highest death rates among newborns, the elderly and adults with chronic lung diseases.

Technology

Dr. Voelker’s lab at National Jewish Health has demonstrated the anti-inflammatory and anti-viral properties of unsaturated phosphatidylglycerols (PGs). PGs markedly attenuate pro-inflammatory cytokine production (IL-6, IL8) induced by RSV, and prevent viral replication in human bronchial epithelium. In addition, these researchers have shown that PGs prevent the intercellular spreading of the RSV virus, after infection is established. Studies with mice reveal that treatment with PGs, at the time of viral challenge, dramatically reduces RSV infection.

Further studies by these scientists have also shown that PG attenuates influenza virus induced cytokine production in human bronchial epithelial cells; and intranasal administration of PG suppresses influenza A virus infection in mice.

The Voelker laboratory has also created 4 novel compounds with similar activity to that of PGs. These novel compounds block RSV and influenza A attachment to epithelial cells in vitro without apparent toxicity.

Potential Applications

Respiratory Syncytial Virus (RSV), influenza A virus, rhinovirus, sepsis-induced ARDS, asthma, reducing the effects of inflammation during mechanical ventilation, chronic bronchitis, COPD, cystic fibrosis, idiopathic pulmonary fibrosis.

State of Development 

Four novel compounds are undergoing a toxicology study with a mouse model of RSV infection.

Publications

    • Kuronuma et al. J Biol Chem. 2009 Sep 18;284(38):25488-500. Epub 2009 Jul 7. PMID: 19584052
    • Numata et al. Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):320-5. Epub 2009 Dec 22. PMID: 20080799
    • Kandasamy et al. J Biol Chem 286:7841, 2011 PMID: 21205826
    • Numata et al. Am J Respir Cell Mol Biol. 2011 PMID: 22052877

    Patent Status
    Issued U.S. Patent #8,367,643. International patents pending. 

    Inventors
    Dennis R. Voelker, PhD
       

    Licensing Status - Available for licensing.  

     

    For Further Information, Contact:

    Emmanuel Hilaire, PhD
    Manager
    Technology Transfer Office
    National Jewish Health
    1400 Jackson Street, Room M206b
    Denver, CO 80206
    Voice: 303.398.1262
    Fax: 303.270.2352
    [email protected]

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