A molecular model of the uricase tetramer.
Uricase converts the poorly soluble uric acid into the highly soluble allantoin, which is easily removed from the body by the kidneys. Because uricase is a foreign protein, it is highly immunogenic. Thus, when administered to humans, unmodified uricase results in the rapid development of antibodies against it, which can rapidly clear the enzyme from the circulation or block its activity. Therefore, unmodified uricases can be used for extremely limited duration before they loose effectiveness.
Pegylation, which results in the attachment of long strands of poly(ethylene) glycol or PEG to a drug, can improve the characteristics of the drug. In the case of uricase, pegylation lengthens the amount of time the enzyme will circulate in the blood stream, thus reducing the frequency of injections needed. Pegylation can also decrease the immunogenicity of a foreign protein, delaying the development of antibodies and reducing the ability of those antibodies to band and remove the drug. We have evidence that both of these mechanisms contribute to the profile of pegsitacase (formerly Uricase-PEG 20).
See How Pegsitacase Works >>