NIH funds study of new antibiotics to combat food-borne disease

A research team led by polymer scientist Gregory Tew that includes biotech firm PolyMedix, Inc. of Radnor, Pa., has received a first-year, $977,658 grant to study and develop new antibiotics against food-borne and related illnesses. Funding, to be shared by the University and PolyMedix, is from the National Institutes of Health’s Cooperative Research Partnerships for Biodefense and Emerging Infectious Disease.

The grant recommends funding for four more years based on performance and fund availability, which would bring the five-year total to $6.6 million, of which UMass Amherst would receive $3.1 million. PolyMedix has developed a promising new antimicrobial compound that imitates a naturally occurring protein called defensin, which attacks bacteria, fungi and many viruses. Tew, a co-founder of PolyMedix and member of its scientific advisory board, says, “This grant will allow us to expand the chemical landscape of antimicrobial peptide mimics with a focus on important food-borne illnesses caused by Gram-negative pathogens.”

The campus research team, which includes organic chemists, microbiologists, biophysicists and immunologists, will build on earlier work by Tew in his polymer science lab, where he and colleagues have developed synthetic molecules known as antimicrobial oligomers (AMO). They behave like a class of natural molecules known as host-defense peptides (HDP) such as defensin. Tew and colleagues chose to mimic HDPs because they display “very broad spectrum action against bacteria, yeast, fungus and even viruses” and have a low propensity to develop antibiotic resistance, an increasingly valuable quality, he says. Because the natural HDPs have many interesting properties, mimicking them in simpler chemical structures is both a fundamentally important scientific challenge as well as a technological opportunity, Tew adds.

This grant will allow the researchers to explore new chemical structures; thereby increasing the number of molecules that mimic HDP activity. In addition, the project will enable new insight into how these new synthetic AMOs clear infection. Using a combination of basic biophysical methods and new immunological models, Tew and colleagues hope to provide unprecedented insight into how the antibiotic candidates eliminate infections in animals. Specific microbes of interest include Salmonella, K. pneumonia, and E. coli.

Medical interest in AMOs is not new, but it has run into some challenges Tew and colleagues hope to address. For example, despite extensive efforts by drug and biotechnology companies, no one has yet found a way to administer AMOs intravenously to treat infections. The UMass Amherst scientists hope a synthetic, non-toxic alternative can not only address this, but lower material costs and tackle problems of toxicity, limited efficacy and limited tissue distribution.

Nicholas Landekic, president and CEO of PolyMedix, notes that the NIH grant, the company’s ninth, will help identify the next generations of antibiotics for treating drug-resistant bacteria and emerging infections. The firm has a defensin-mimetic AMO, PMX-30063, currently in Phase I clinical human trials and hopes it can soon be tested against methicillin-resistant Staphylococcus aureus (MRSA) infections. Late last year, PolyMedix reported the first positive in-man results.

“In difficult economic times, this support is particularly important and appreciated,” notes Landekic, “and it enables work that would otherwise not be possible. We are proud to receive this important grant and to continue our work with the University of Massachusetts Amherst and Dr. Gregory Tew.” For his part, Tew says the grant recognizes “an outstanding partnership” between UMass Amherst and PolyMedix.

July 27, 2009.

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