CLINICAL FOCUS

The epithelial barrier is our first line of defence against invading microorganisms. Epithelial cells express host defense peptides in all surfaces of the body, including the skin, eyes, lungs, gut and urinary tract. The human body produces multiple different host defense peptides with varied structural features and specifics. The host defense peptides kill the bacteria primarily by destroying the bacterial membranes. The peptides join forces, thus forming an effective and broad front-line defense mechanism that the bacteria must overcome in order to infect humans.

Some virulent strains of bacteria (professional pathogens) are able to turn off the synthesis of the host defense peptide arsenal (Figure 1), thus causing infections. Akthelia has identified active pharmaceutical ingredients (APIs) which are capable of inducing the synthesis of the peptides and thus counteract the effects of the bacteria. Akthelia is committed to developing these agents into therapeutic drugs.

The proposed host defense microbial treatment is a paradigm shift in the treatment of infections. At pharmacologically relevant concentrations the active ingredients have minimal direct effects on the microbes. The therapeutic effect is manifested when the active ingredient interacts with a viable epithelium, which in turn increases the production of AMPs - the true microbicidal agents. A very important and beneficial feature of this novel treatment method is the low probability of microbial resistance since with the many different peptides induced there is no single solution for the bacteria to avoid destruction. This is in sharp contrast to classical antibiotics where natural selection enriches for the resistant microbial population.