Chemokine-receptor expression profiling in biological samples from human clinical trials

Project Summary AbstractChronic pain is a major healthcare burdenrepresenting economic costs of up to $B per yearmore than cancerdiabetesand heart diseasePain is a highly heterogeneous condition comprising neuropathicnociceptive and inflammatory componentsand patient responses to currently available drugs vary greatlyA very promising approach to target various forms of pain is through antagonism of key players in neuro inflammationSpecificallythe chemokine receptor systema complex network of overdifferent receptors and overligandsis integral to neuroinflammatory processes and the pharmaceutical industry had been very active in developing compounds targeting individual receptors in the networkHoweverthe biological complexityligand promiscuityand receptor redundancy of the chemokine receptor system has precluded successful clinical development of the compounds and many pharma have exited the pain therapeutic areaA major limitation of successful targeting of this network is sufficient understanding of the molecular and cellular dynamics of the chemokine networkand how specific receptors vary in chronic pain conditionsIn a funded SBIR studywe aim to determine the genetic expression of a heterogenous chemokine receptor utilizing human clinical samples collected in a clinical trial evaluating a receptor antagonistThis application is to participate in i Corps program at NIH Project NarrativeChronic pain results in sufferingreduced quality of lifeand significant healthcare burdenswith an estimated annual economic cost up to $BNeuropathy and neuroinflammatory processes affected by the chemokine receptor system represent a promising area to treat various forms of chronic pain and these have attracted large investments in recent yearsWe aim to develop a deeper biological understanding of the receptor dynamics in this system using human samples collected from clinical trials evaluating an investigational drug antagonist for the receptorThis application is to participate in i Corps program at NIH