A comprehensive review of interventions in the NOD mouse and implications for translation.
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.
Shoda
Lisl K M
LK
Entelos Inc., Foster City, California 94404, USA. shoda@entelos.com
Young
Daniel L
DL
Ramanujan
Saroja
S
Whiting
Chan C
CC
Atkinson
Mark A
MA
Bluestone
Jeffrey A
JA
Eisenbarth
George S
GS
Mathis
Diane
D
Rossini
Aldo A
AA
Campbell
Scott E
SE
Kahn
Richard
R
Kreuwel
Huub T C
HT
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