title: Modeling non-clinical and clinical drug tests in Gaucher disease.
abstract: There is need for modeling biological systems to accelerate drug pipelines for treating metabolic diseases. The eliglustat treatment for Gaucher disease is approved by the FDA with a companion genomic test. The Transcriptome-To-Metabolome™ biosimulation technology was used to model, in silico, a standard non-clinical eliglustat test with an in vitro canine kidney cell system over-expressing a human gene; and a clinical test using human fibroblasts from control and Gaucher disease subjects. Protein homology modeling and docking studies were included to gather affinity parameters for the kinetic metabolic model. Pharmacodynamics and metabolomics analyses of the results replicated published findings and demonstrated that processing and transport of lysosomal proteins alone cannot explain the metabolic disorder. This technology shows promise for application to other diseases.
authors.forename: Clyde F
authors.initials: CF
authors.lastname: Phelix
authors.forename: Allen K
authors.initials: AK
authors.lastname: Bourdon
authors.forename: Greg
authors.initials: G
authors.lastname: Villareal
authors.forename: Richard G
authors.initials: RG
authors.lastname: LeBaron
mesh_terms: D000818:Animals; D004285:Dogs; D004791:Enzyme Inhibitors; D005347:Fibroblasts; D005776:Gaucher Disease / Q000188:drug therapy; D006801:Humans; D007700:Kinetics; D011759:Pyrrolidines
chemical_list: D004791:Enzyme Inhibitors; D011759:Pyrrolidines