01572: Development of a Novel Therapeutic For Neutrophil-Driven Inflammation
Grant Status: Closed
White blood cells called neutrophils are essential for host defense. When activated, they produce an array of proteins and other molecules that kill invading microbes. However, these products also are quite damaging to host tissues. Neutrophil functions are often not regulated properly in acute and chronic inflammatory diseases of the respiratory tract and other body systems; in fact, neutrophils account for much of the damage in many inflammatory diseases. We have developed a novel compound called the MANS peptide that inhibits the protein called MARCKS in human neutrophils. Inhibition of the MARCKS protein with MANS potently blocks human neutrophil activation. Our collaborator Adler is developing derivatives of the MANS peptide for treatment of chronic lung inflammation in people. In this application we propose to determine whether the MANS peptide has similar effects on canine neutrophil activation. If our hypothesis is correct, then MANS and compounds derived from MANS are a novel drugs that have the potential for treating serious inflammatory diseases of the canine respiratory tract and perhaps other body systems. Progress to date has demonstrated that the MARCKS protein does indeed regulate the mechanisms that govern neutrophil influx into tissues during inflammation. Thus, the MANS peptide in principle has the potential to decrease this process, reducing inflammation.
Manuscript in preparation.
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