Currently there is strong interest in natural proteins, such as thrombospondins, Platelet factor-4, angiostatin and endostatin, as therapeutics for cancer and other diseases, because of the lack of side effects and drug resistance development. Phase I studies demonstrated that the zebrafish is a viable whole animal model for screening proteins and chemical compounds for anti-angiogenic effects. An enzyme assay was successfully developed to quantify vessel growth and a clear dose response was observed for several drugs. In Phase II research, the enzyme assay will be used to determine optimum assay conditions for protein drug testing, and then used to screen therapeutic drug candidates. Since comprehensive commercial drug screening programs rely on a number of confirmatory assays to assess drug specificity, Phase II research will also develop a family of vessel specific monoclonal antibody (mAb) based assays to complement the enzyme assay. Phase II research will also use the vessel specific mAb based markers to elucidate the mechanisms of angiogenesis.
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