a plant-derived recombinant human glucocerebrosidase enzyme—a preclinical and phase i investigation基于植物重组人类葡糖脑苷脂酶enzyme-a临床前和第一阶段的调查.pdfVIP

A Plant-Derived Recombinant Human Glucocerebrosidase Enzyme—A Preclinical and Phase I Investigation 1 1 1 1 1 David Aviezer , Einat Brill-Almon , Yoseph Shaaltiel , Sharon Hashmueli , Daniel Bartfeld , Sarah 2 2 2 3 2 Mizrachi , Yael Liberman , Arnold Freeman , Ari Zimran , Eithan Galun * 1 Protalix Biotherapeutics, Science Park, Carmiel, Israel, 2 Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Hospital, Jerusalem, Israel, 3 Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel Abstract Gaucher disease is a progressive lysosomal storage disorder caused by the deficiency of glucocerebrosidase leading to the dysfunction in multiple organ systems. Intravenous enzyme replacement is the accepted standard of treatment. In the current report, we evaluate the safety and pharmacokinetics of a novel human recombinant glucocerebrosidase enzyme expressed in transformed plant cells (prGCD), administered to primates and human subjects. Short term (28 days) and long term (9 months) repeated injections with a standard dose of 60 Units/kg and a high dose of 300 Units/kg were administered to monkeys (n = 4/sex/dose). Neither clinical drug-related adverse effects nor neutralizing antibodies were detected in the animals. In a phase I clinical trial, six healthy volunteers were treated by intravenous infusions with escalating single doses of prGCD. Doses of up to 60 Units/kg were administered at weekly intervals. prGCD infusions were very well tolerated. Anti-prGCD antibodies were not detected. The pharmacokinetic profile of the prGCD reveale