Intellectual Property Office

Non-Confidential Disclosures

"Natural Compound Suppresses lipopolysaccharide (LPS) -Mediated TNF-Alpha"

PSU Inv. Disc. No 1990

Field of the Invention:

Therapeutics for Septic Shock and other Immunological Diseases and Cancers

Inventors:

K. Feldman

Background:

The acute overproduction of tumor necrosis factor-alpha from peripheral blood mononuclear cells (PBMC’s) is cited in the etiology of septic shock (bacterial sepsis). This lethal disease strikes five out of every 1000 hospital admits in the United States and has a mortality rate approaching forty percent (40%) depending upon the underlying infection. TNF-alpha secretion results from exposure of PBMC’s to the lipid A portion of lipopolysaccharide (LPS), a cell wall component of gram negative bacteria (e.g., E. coli, K. pneumonia, P. aeruginosa). Consequently, chemical or biological agents which suppress LPS-induced TNF-alpha overproduction may have value in ameliorating the septic shock response. Current approaches to inhibit lipopolysaccharide (LPS) – induced sepsis include: 1) Using LPS antagonists which presumably block the lipid A/receptor interactions, or 2) monoclonal antibodies which are designed to sequester various components of the septic shock response (LPS, TNS-alpha, TNF-alpha receptors, LPS receptors, etc.)  The former strategy relies on either lipid A analogs/derivatives which are quite potent but so structurally complex as to render scale-up production problematical, or on small molecule agents which are more accessible but much less potent. The latter approach is hampered by cost concerns and ultimately has been disappointing in in vivo efficacy trials. In no case has a compound reached market.

Invention description:

A member of a family of plant produced compounds has been shown in in vitro studies to potentially act as an LPS antagonist. As shown in the attached non-confidential graph, the addition of this compound rapidly quenched the TNF-alpha secretion from human PBMC’s stimulated by the addition of LPS. Results from in-vivo, rat experiment should be forthcoming in the near future. The Penn State researchers have developed a process to synthesize this compound as well as analogs thereof that is straightforward and economical. The family of compounds typically exhibit inherently low cytotoxity.

Contact:

Mr. Matthew Smith
Sr. Technology Licensing Officer
Intellectual Property Office
113 Technology Center
The Pennsylvania State Univ.
University Park, PA 16802-7000
Phone: (814) 863-1122
Fax: (814) 865-3591
E-mail: mds126@psu.edu