However, the extent to which MGMT influences the treatment of brain metastases with alkylating agents needs to be explored in future studies. This suggests that brain metastases may be a potential target for therapy with alkylating substances. Showing a clear correlation between homogeneous MGMT immunoreactivity and an unmethylated MGMT promoter, we hypothesize that MGMT immunohistochemistry – as a screening method – could be a helpful diagnostic tool to identify those tumors that probably will not benefit from the use of alkylating agents like temozolomide. Clinical data is necessary to validate this hypothesis. However, the discrepancy between promoter methylation and MGMT negativity necessitates combined immunostaining and methylation specific PCR. Since its introduction in 1991, glucocerebrosidase enzyme replacement therapy has become the standard of care for patients with symptomatic Gaucher disease due to its safety and efficacy profile. The success of ERT in Gaucher disease ultimately led to the development of recombinant enzyme treatments for other lysosomal storage diseases such as Fabry, MPS-I, MPS-II, MPS-IV,NSC23766 Pompe and other lysosomal storage disorders. Currently, the enzymes used for treating lysosomal storage disorders in general and in Gauchers disease in particular are expressed in mammalian, Chinese Hamster ovary cells. However, production of this enzyme in mammalian cells is expensive, and the high cost of the approved recombinant glucocerebrosidase for treating Gaucher’s disease,SCH 900776 (CAS:891494-64-7) is raising public concern. In an attempt to offer an alternative source for the production of the glucocerebrosidase enzyme, we have developed a biotechnological expression platform which is based on the industrial scale expression of human recombinant proteins in genetically engineered plant cells. The plant cell technology allows for a cost efficient production system. In addition, the entire manufacturing process is free from any animal-derived components, complementing processing safety advantages as well. prGCD, is the most clinically advanced recombinant plant system expressed protein to undergo phase III clinical trials and its chemical, functional and genetic characterization, including the full amino-acid sequence and its three dimensional crystal structure have recently been described. Following the successful completion of nonclinical safety toxicology studies, which included a single dose study in rodents and a 28-day acute safety toxicology study in primates with daily dosing of prGCD, regulatory approval for conducting a Phase I clinical trial was allowed by the FDA. The clinical study in healthy human volunteers was designed to evaluate the safety of three escalating doses of prGCD and to determine the pharmacokinetics profile of the drug. In addition, a nine-month chronic safety toxicology study in primates with dosing once every two weeks, mimicking the proposed clinical regime of prGCD, was also performed.This study was a prerequisite for the initiation of an advanced Phase III clinical trial, which will address the continuing safety of chronic administration of prGCD. The primary objective of this Phase I clinical trial was to determine the safety of recombinant plant cell expressed glucocerebrosidase in healthy volunteers.