Novel TLR Inhibitors Prevent Respiratory Syncytial Virus Infection In Vivo

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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
The lab is now working on continuous delivery systems for liposomes using aerosol techniques, and will use this method to improve the window of efficacy of the PGs. 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

  • Numata et al. J Lipid Res. 2013 Aug;54(8):2133-43. PMID: 23749985

  • Numata et al. Int J Nanomedicine. 2013;8:1417-27. Epub 2013 Apr 15. PMID: 23717040

  • Numata et al. Expert Rev Respir Med 2012 Jun;6(3):243-6. PMID: 22788936

  • Numata et al. J Lipid Res. 2015 Mar;56(3):578-87. PMID: 25561461

  • Numata et al. J Biol Chem. 2019 Dec 27;RA119.012053. PMID: 31882535

 

Patent Status
Issued U.S. Patents #10,532,066, #9,861,649, #8,796,243 and #8,367,643. 

 

Inventors
Dennis R. Voelker, PhD., Mari Numata-Nakamura, MD, PhD.

 

Licensing Status
This technology is available for licensing in all fields of use except human therapeutics.

 

For Further Information, Contact:
Emmanuel Hilaire, PhD
Director
Technology Transfer Office
National Jewish Health
1400 Jackson Street, Room M206b
Denver, CO 80206
Voice: 303.398.1262
Fax: 303.270.2352
HilaireE@njhealth.org

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