A plant-derived recombinant human glucocerebrosidase enzyme--a preclinical and phase I investigation

PLoS One. 2009;4(3):e4792. doi: 10.1371/journal.pone.0004792. Epub 2009 Mar 11.


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 revealed a prolonged half-life compared to imiglucerase, the commercial enzyme that is manufactured in a costly mammalian cell system. These studies demonstrate the safety and lack of immunogenicity of prGCD. Following these encouraging results, a pivotal phase III clinical trial for prGCD was FDA approved and is currently ongoing.

Trial registration: ClinicalTrials.gov NCT00258778.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antibody Formation
  • Cells, Cultured / enzymology
  • Clinical Trials, Phase III as Topic
  • Daucus carota / cytology
  • Drug Evaluation, Preclinical
  • Female
  • Gaucher Disease / drug therapy*
  • Gaucher Disease / enzymology
  • Gaucher Disease / genetics
  • Glucosylceramidase / adverse effects
  • Glucosylceramidase / economics
  • Glucosylceramidase / genetics
  • Glucosylceramidase / immunology
  • Glucosylceramidase / isolation & purification
  • Glucosylceramidase / pharmacokinetics
  • Glucosylceramidase / therapeutic use*
  • Half-Life
  • Humans
  • Infusions, Intravenous
  • Macaca fascicularis
  • Male
  • Neutralization Tests
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / economics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / isolation & purification
  • Recombinant Fusion Proteins / pharmacokinetics
  • Recombinant Fusion Proteins / therapeutic use
  • Transfection
  • Young Adult


  • Recombinant Fusion Proteins
  • Glucosylceramidase
  • imiglucerase

Associated data

  • ClinicalTrials.gov/NCT00258778