Canadian team announce major development in boosting human immunity with laboratory designed peptides

Robert Hancock, principal investigator and Canada Research Chair in Pathogenomics and Antimicrobials has lead a team at the U of British Columbia (UBC) in conjunction with UBC spin off Inimex Pharmaceuticals (Founders - Hancock and co-author Brett Finlay, a UBC microbiologist) - and summarises his view of the future of antiobiotic treatments ;

"Antibiotics are now under threat because of the explosion in antibiotic-resistant bacteria. A third of all deaths on this planet are the result of infection so there is an urgent need to create new therapies,"

This week they have announced a innovative method of attacking the scourges that stalk North American hospitals (and elsewhere) - the "hospital superbugs"

Instead of attacking the chinks in the biochemistry of the bacteria, they have been investigating with some reported success, ways to re-inforce the natural ("innate") immune response of the patient and claim that this novel technique," has not been reported previously"

They have identified a peptide ( simply, a short chain of amino acids > 50 bases (ish) - distinct from polypeptides or proteins which are long chains) which they call the innate defense regulator peptide (IDR-1). This appears to increase the natural ummune response without triggering harmful inflammation, and offer protection both before and after infection.

The great virtue of this approach is that in use it will not act on the bacteria directly and therefore it is unlikely bacteria will become resistant to it.

Effectiveness was tested in mouse models against Staphylococcus aureus including MRSA; a superbug called vancomycin-resistant Enterococcus (VRE); and Salmonella. In Staph and VRE infections, although bacteria were not completely eradicated, IDR-1 significantly reduced bacteria counts and mortality, when given either 24-48 hours before or four hours after infection began. In Salmonella, the peptide offered significant protection when administered prior to infection setting in.

The team claim that IDR-1 activates several signaling pathways to stimulate infection-clearing chemokines -- a chemical mediator that mobilizes immune response. (see Footnote)

In use they see the peptide could be used in conjunction with or as a supplement to antibiotics especailly for common hospital infections such as ventilator associated pneumonia, post-surgical infections, high dose chemotherapy and infections arising from insertion of catheters or other medical devices.

Of course this is potentially a very profitable new therapy , they provide the latest figures on North American Hospital Acquired Infections.

2 Mn. cases of antibiotic-resistant infection in hospitals kill approximately 70,000 people annually in North America, which broadly agrees with UK experience.

Hospital-based methicillin-resistant Staphylococcus aureus (MRSA) alone causes an estimated 100,000 hard-to-treat infections annually and is now seen in community-based infections, such as boils and abscesses or life-threatening bloodstream infections.

"Salmonella causes 1.3 million infections and up to 100 deaths every year in the U.S. We're looking at a crisis in 10 years as most bugs will be resistant to most antibiotics.

The team expect it will be about 12-15 months before the discovery is introduced into human clinical trials.... however it is not impossible that the large pharma companies are already having friendly conversations with Inimex and it's founders who have announced that they currently have in the pipeline an IDR product IMX942 for hospital bacterial infections. Should you be interested, a trip round their excellent website would be very instructive, especially the quality of scientific backing, financial muscle and pharma drug development.

The discovery, was published in the March 25th issue of the journal Nature Biotechnology.(doi:10.1038/nbt1288) (subscription for full article)
An anti-infective peptide that selectively modulates the innate immune response

FOOTNOTE

"Because protection by IDR-1 was prevented by in vivo depletion of monocytes and macrophages, but not neutrophils or B- and T-lymphocytes, we conclude that monocytes and macrophages are key effector cells. IDR-1 was not directly antimicrobial: gene and protein expression analysis in human and mouse monocytes and macrophages indicated that IDR-1, acting through mitogen-activated protein kinase and other signaling pathways, enhanced the levels of monocyte chemokines while reducing pro-inflammatory cytokine responses."