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 - Published U.S. Patent application #20080242640. 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
HilaireE@njhealth.org
