Playing Copycat with Mother Nature

This story begins with frogs and ends with perhaps a true life-saving product.  A lily pad is a fine place to perch in the moonlight and broadcast mating calls if you’re a frog, but the typical picturesque lily pond is a cesspool of microorganisms.  If a human swam in similar water, he would risk serious illness or worse.

How do frogs manage to live happily in such filthy water?  In 1986 a scientist named Michael Zasloff found the answer.  The skin of the frog harbors armies of protein-like germ fighters.  Dr. Zasloff was able to isolate a molecule, which he named magainin (Hebrew for “shield”).  Magainin has the instincts of a secret service agent.  Squads of these agents patrol a frog’s skin, where they attack and destroy the cells of bacteria that threaten infection. This was the first of the class of agents called host defense proteins, which have since then been found in virtually all higher life forms, including people, where they are called “defensins” These host-defense proteins form the innate immune system which all higher life uses as a first line of defense against bacteria.

Bacterial infections are now the fourth leading cause of death in the U.S., and one of the fastest growing causes of death, with about 100,000 deaths each year in the U.S. alone. Drug-resistant bacterial infections are one of the most significant problems facing medicine and our society today. There are many strains of bacteria that are now resistant to multiple classes of antibiotics, with no effective treatments available.

The prospects of creating new germ fighters from this discovery are vast.  The host defense proteins work fundamentally differently from all other known antibiotics: they directly punch holes in bacterial cell membranes, via a biophysical rather than biochemical mechanism of action. One of the most intriguing possibilities is creating new forms of antibiotics to fight bacteria that have become resistant, or immune, to conventional antibiotics. Studies show that bacteria have little, or no ability, to resist antimicrobial peptides.

Initial efforts to use nature's molecular germ fighters were based on the natural animal host defense proteins themselves. However, the natural peptides came with built-in obstacles to practical use.  Natural peptides, as well as their synthetic analogues, are expensive to prepare and difficult to produce on a large scale, which limits their potential use – they were not able to be successfully developed into drugs. This extremely promising mechanism was thus untapped -  until now.

Scientists at the University of Pennsylvania, including Dr. William DeGrado, a member of the National Academy of Sciences, used supercomputers to design and create synthetic small organic molecules and polymers — much easier to make than peptides — but which would have the same mechanism of action as the host defense proteins and with similar germ-fighting ability.

Based on the success of this work, the University of Pennsylvania filed for several patents, which spun off a biotech company called PolyMedix, to investigate the possibilities for useful applications as both  novel therapeutic antibiotic drugs, and as antimicrobial polymers for biomaterials applications.

The company, now based in Radnor, Pennsylvania, received regulatory clearance to initiate a Phase I clinical trial from Health Canada. These investigational antibiotic agents are the first of their kind that directly address the serious medical problem of bacterial drug resistance: compounds that punch holes in bacterial cell membranes, and work in a way that makes resistance unlikely to develop. PolyMedix is also working to develop their antimicrobial polymers as additives for materials such as plastics, coatings, toys, and medical devices to create self-sterilizing materials and surfaces.

We invite you to speak with Nick Landekic, PolyMedix’s highly knowledgeable and articulate Chief Executive Officer. We also encourage you to speak with Dr. DeGrado.  Mr. Landekic and Dr. DeGrado can discuss how PolyMedix’s research may constitute a major breakthrough in the battle to combat drug-resistant bacterial infections, which could potentially save tens of thousands of lives each year.