Reproductive and developmental toxicology studies with gantenerumab in PS2APP transgenic mice

Reprod Toxicol. 2017 Oct:73:362-371. doi: 10.1016/j.reprotox.2017.07.014. Epub 2017 Jul 25.

Abstract

Gantenerumab is intended for the treatment of Alzheimer's disease. It is a fully human recombinant monoclonal IgG1 which binds aggregated forms of amyloid beta such as Aβ oligomers, fibrils and neuritic amyloid plaques. A full package of developmental and reproductive toxicity (DART) studies was performed in the PS2APP double-transgenic mouse model of Alzheimer's disease. A combined fertility and embryo fetal development study and a pre-and post-natal development study were performed. The PS2APP mouse model allowed a more complete DART evaluation than would have been possible in conventional species or strains which do not express the target antigen of gantenerumab. No developmental or reproductive hazards were identified.

Keywords: Dart; Disease model; Monoclonal antibody; PS2APP mouse; Safety testing.

MeSH terms

  • Alzheimer Disease
  • Amyloid beta-Peptides / immunology
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / toxicity*
  • Antibodies, Monoclonal, Humanized
  • Disease Models, Animal
  • Embryo, Mammalian / drug effects
  • Embryonic Development / drug effects
  • Female
  • Fertility / drug effects
  • Fetal Development / drug effects
  • Fetus / drug effects
  • Immunoglobulin G / immunology
  • Male
  • Mice, Transgenic
  • Presenilin-2 / genetics

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin G
  • PSEN2 protein, human
  • Presenilin-2
  • gantenerumab