Tanezumab, an antibody to nerve growth factor, was administered to pregnant 
cynomolgus monkeys at 0, 0.5, 4, and 30 mg/kg weekly, beginning gestation day 
(GD) 20 through parturition (∼GD165). Maternal tanezumab administration appeared 
to increase stillbirths and infant mortality, but no consistent pattern of gross 
and/or microscopic change was detected to explain the mortality. Offspring 
exposed in utero were evaluated at 12 months of age using light microscopy (all 
tissues), stereology (basal forebrain cholinergic and dorsal root ganglia 
neurons), and morphometry (sural nerve). Light microscopy revealed decreased 
number of neurons in sympathetic ganglia (superior mesenteric, cervicothoracic, 
and ganglia in the thoracic sympathetic trunk). Stereologic assessment indicated 
an overall decrease in dorsal root ganglion (thoracic) volume and number of 
neurons in animals exposed to tanezumab 4 mg/kg (n = 9) and 30 mg/kg (n = 1). At 
all tanezumab doses, the sural nerve was small due to decreases in myelinated 
and unmyelinated axons. Existing axons/myelin sheaths appeared normal when 
viewed with light and transmission electron microscopy. There was no indication 
of tanezumab-related, active neuron/nerve fiber degeneration/necrosis in any 
tissue, indicating decreased sensory/sympathetic neurons and axonal changes were 
due to hypoplasia or atrophy. These changes in the sensory and sympathetic 
portions of the peripheral nervous system suggest some degree of developmental 
neurotoxicity, although what effect, if any, the changes had on normal function 
and survival was not apparent. Overall, these changes were consistent with 
published data from rodent studies.