Dosing and timing effects of anti-CD40L therapy: predictions from a mathematical model of type 1 diabetes.
Several publications describing the use of anti-CD40L monoclonal antibodies (anti-CD40L) for the treatment of type 1 diabetes in non-obese diabetic (NOD) mice have reported different treatment responses to similar protocols. The Entelos Type 1 Diabetes PhysioLab platform, a dynamic large-scale mathematical model of the pathogenesis of type 1 diabetes, was used to study the effects of anti-CD40L therapy in silico. An examination of the impact of pharmacokinetic variability and the heterogeneity of disease progression rate on therapeutic outcome provided insights that could reconcile the apparently conflicting data. Optimal treatment protocols were identified by exploring the dynamics of key pathophysiological pathways.
Gadkar
Kapil G
KG
Entelos, Inc., 110 Marsh Drive, Foster City, CA 94404, USA.
Shoda
Lisl K M
LK
Kreuwel
Huub T C
HT
Ramanujan
Saroja
S
Zheng
Yanan
Y
Whiting
Chan C
CC
Young
Daniel L
DL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D023201:CD40 Ligand / Q000276:immunology*; D003198:Computer Simulation; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology*; D004334:Drug Administration Schedule; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D008954:Models, Biological
D000911:Antibodies, Monoclonal; D023201:CD40 Ligand