Dr. Miles Nunn, Akari’s Chief Scientific Officer, made the original discovery of nomacopan and other inhibitory proteins while studying the structural and functional interactions between parasite-derived molecules and host defense responses, in particular the early mediators of inflammation including the complement, eicosanoid and bioamine systems.
Nomacopan is derived from a protein originally discovered in the saliva of the Ornithodoros moubata tick. Over 300 million years of blood feeding has resulted in ticks selected to produce inhibitors that bind tightly and very specifically to key highly-conserved inflammatory mediators. Nomacopan and other molecules derived from ticks are required for the parasite to obtain repeated blood meals to fuel development and reproduction. Therefore, the molecules ticks produce need to be well-tolerated and maintain their inhibitory effect in hosts repeatedly exposed to the same molecule during tick feeding; otherwise ticks, which are obligate blood feeders, would be unable to reproduce. The evidence to date from preclinical and human clinical testing strongly support the safety, tolerability and continued functionality of tick proteins administered chronically.
Ticks target highly conserved components of the immune system that have conserved central roles in the development of immune responses. The ultimate cause of this specificity may be that ticks are “sit and wait” predators, which means when a host passes close to the tick it is advantageous to be able to feed on it – whatever the host may be. Targets that have conserved central roles in the development of inflammation and elaboration of the immune response may therefore be favored by natural selection as inhibitors which target them will have similar effects on most host species.
Ticks also target mediators of inflammation that act early in the development of an immune response or which amplify immune responses. If they are able to stop inflammation early or disrupt the signals that drive inflammation, ticks do not then have to counteract a full-blown adaptive immune response.
These underlying principles driven by natural selection – tolerability, specificity, key mediators – are why Akari believes ticks are an excellent source of potential therapeutic molecules. Our focus on early mediators of acute and chronic inflammation is grounded in our understanding they have causative roles in the pathology of many diseases, and that inhibition of early mediators will prevent initiation and continual amplification of processes that cause disease.