Transferangebote:

 

Alle Institute dieser Sektion

Sepsis / Antimicrobial peptides

Synthetic Antimicrobial and LPS-Neutralizing Peptides (SALP) for Prevention and Treatment of Sepsis

Ansprechpartner

Dr. Torsten Stachelhaus, Ascenion, stachelhaus@ascenion.de

Kurzbeschreibung

Challenge

Sepsis is one of the leading causes for mortality in industrialized countries. In the US approximately 750.000 patients per year contract sepsis, 215.000 of these patients die. The estimated costs for treatment are 17 billion US Dollar per year (Angus DC, Crit Care Med 2001). Still, existing therapies do not address one of the major underlying triggers for sepsis: free lipopolysaccharides (LPS), released from bacteria by the action of the immune system or simply by cell division. Despite of recently improved diagnostic and therapeutic options, there is a major need for new and efficient active agents, which not only kill the bacteria, but additionally neutralize free endotoxins.

Technology
The technology meets this medical need by disclosing new synthetic peptides (SALPs) which both kill bacteria and efficiently neutralize free LPS. These SALPs were designed and synthesized based on the insight of comprehensive biophysical studies of natural occurring antimicrobial proteins (e.g. porcine NK-lysin or human granulysin) in which the essential parameters for LPS-neutralization were determined. Among these parameters are the surface potential of the LPS head group, the fluidity of the lipid A acyl chains and the lipid A aggregate structure.
Developmental Status
Toxicity of new SALPs was tested in vitro using different human cell types (erythrocytes, PBMCs, Jurkat, HepG2 and epithelial cells). No toxic effect was observed in therapeutically relevant concentrations. Antibacterial activity was determined by microdilution susceptibility assays following the recommendations of the Clinical Standards Institute using E. coli, MRSA and other strains. In addition, strong antiviral activity has already been shown for a variety of viruses (including HIV, Herpes).
LPS-neutralizing activity was tested in vitro (cytokine secretion of human mononuclear cells) and in vivo. The results from a murine model for endotoxic shock prove that SALPs efficiently neutralize LPS in vivo and reduce mortality as good or even better as  the accepted ‘gold standard’ polymixin B.
Currently, additional preclinical experiments are conducted to explore SALP-properties in other in vitro and in vivo models of sepsis. A GLP-compliant ADME/Tox study is scheduled for 2010.

Technologie

Entwicklungsstand

The new SALPs are offered for in-licensing or co-development.

 

Anschrift

  • Parkallee 1-40
  • 23845 Borstel

Ansprechpartner

 
interner Link: Start Sprungmarke externer Link: http://www.bmwi.de/, öffnet in einem neuen Fenster externer Link: http://www.signo-deutschland.de/hochschulen, öffnet in einem neuen Fenster