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

Technology Benefits

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

Technology Application

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.

Detailed Technology Description

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.

Supplementary Information

Patent Number: US20080242640A1
Application Number: US200857967A
Inventor: Voelker, Dennis R.
Priority Date: 29 Mar 2007
Priority Number: US20080242640A1
Application Date: 28 Mar 2008
Publication Date: 2 Oct 2008
IPC Current: A61K003166 | A61K0031683
US Class: 514120 | 514130
Assignee Applicant: National Jewish Medical and Research Centernver
Title: Surfactant Lipids, Compositions Thereof and Uses Thereof
Usefulness: Surfactant Lipids, Compositions Thereof and Uses Thereof
Summary: The method is useful to inhibit inflammation or pathogen infection, preferably viral infection comprising respiratory syncytial virus infection to the individual, where the inflammation or pathogen infection is associated with a toll-like receptor (TLR) comprising TLR1 (preferred), TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, and TLR10; and the individual is a neonatal infant, who has: an infection, condition or disease associated with TLR2 comprising cytomegalovirus infection, herpes simplex virus infection, measles, a protozoan infection, a fungal infection, and Varicella zoster infection; an infection, condition or disease associated with TLR3 comprising a viral infection and a cancer; an infection, condition or disease associated with TLR6 comprising a bacterial infection, a protozoan infection and a fungal infection; an infection, condition or disease associated with TLR7 comprising an autoimmune disease, a cancer, and a viral infection; an infection, condition or disease associated with TLR8 comprising autoimmune disease, basal cell carcinoma, Bowen's disease, condyloma, genital warts, human immunodeficiency virus (HIV), rhinovirus, parainfluenza virus, Human parechovirus, melanoma, and mollusca contagiosa; and a respiratory disorder comprising adult respiratory distress syndrome (ARDS), acute lung injury (ALI), viral infection associated with asthma, chronic obstructive pulmonary disease (COPD), pneumonia, bronchitis, tuberculosis, reactive airway disease syndrome, interstitial lung disease, rhinitis and parasitic lung disease, and the pathogen infection is human immunodeficiency virus infection, rhinovirus infection, parainfluenza virus infection, human parechorvirus infection, influenza infection, papilloma virus infection and Varicella zoster infection (all claimed).
Novelty: Inhibiting inflammation/pathogen infection, preferably viral infection, comprises administering anionic lipid/related compound, which has hydrophobic portion, negatively charged portion and uncharged, polar portion

Industry

Disease Diagnostic/Treatment

Sub Category

HIV

*Abstract

Dr. VoelkerΓÇÖs 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.

*Principal Investigator

Name: Dennis Voelker, Professor

Department: Department of Medicine

Country/Region

USA