title: A comprehensive review of interventions in the NOD mouse and implications for translation.
abstract: Type 1 diabetes (T1D) animal models such as the nonobese diabetic (NOD) mouse have improved our understanding of disease pathophysiology, but many candidate therapeutics identified therein have failed to prevent/cure human disease. We have performed a comprehensive evaluation of disease-modifying agents tested in the NOD mouse based on treatment timing, duration, study length, and efficacy. Interestingly, some popular tenets regarding NOD interventions were not confirmed: all treatments do not prevent disease, treatment dose and timing strongly influence efficacy, and several therapies have successfully treated overtly diabetic mice. The analysis provides a unique perspective on NOD interventions and suggests that the response of this model to therapeutic interventions can be a useful predictor of the human response as long as careful consideration is given to treatment dose, timing, and protocols; more thorough investigation of these parameters should improve clinical translation.
authors.affiliation: Entelos Inc., Foster City, California 94404, USA. shoda@entelos.com
authors.forename: Lisl K M
authors.initials: LK
authors.lastname: Shoda
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Young
authors.forename: Saroja
authors.initials: S
authors.lastname: Ramanujan
authors.forename: Chan C
authors.initials: CC
authors.lastname: Whiting
authors.forename: Mark A
authors.initials: MA
authors.lastname: Atkinson
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
authors.forename: Aldo A
authors.initials: AA
authors.lastname: Rossini
authors.forename: Scott E
authors.initials: SE
authors.lastname: Campbell
authors.forename: Richard
authors.initials: R
authors.lastname: Kahn
authors.forename: Huub T C
authors.initials: HT
authors.lastname: Kreuwel
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD