title: Anti-NGF monoclonal antibody muMab 911 does not deplete neurons in the superior cervical ganglia of young or old adult rats.
abstract: Nerve growth factor (NGF) blocking therapies are an emerging and effective approach to pain management. However, concerns about the potential for adverse effects on the structure and function of the peripheral nervous system have slowed their development. Early studies using NGF antisera in adult rats reported effects on the size and number of neurons in the sympathetic chain ganglia. In the work described here, both young adult (6-8 week) and fully mature (7-8 month) rats were treated with muMab 911, a selective, murine, anti-NGF monoclonal antibody, to determine if systemic exposures to pharmacologically active levels of antibody for 1 month cause loss of neurons in the sympathetic superior cervical ganglia (SCG). State-of-the-art, unbiased stereology performed by two independent laboratories was used to determine the effects of muMab 911 on SCG neuronal number and size, as well as ganglion size. Following muMab 911 treatment, non-statistically significant trends toward smaller ganglia, and smaller and fewer neurons, were seen when routine, nonspecific stains were used in stereologic assessments. However, when noradrenergic neurons were identified using tyrosine hydroxylase (TH) immunoreactivity, trends toward fewer neurons observed with routine stains were not apparent. The only statistically significant effects detected were lower SCG weights in muMab 911-treated rats, and a smaller volume of TH immunoreactivity in neurons from younger rats treated with muMab 911. These results indicate that therapeutically relevant exposures to the anti-NGF monoclonal antibody muMab 911 for 1 month have no effect on neuron numbers within the SCG from young or old adult rats.
authors.affiliation: Drug Safety R&D, Pfizer Worldwide R&D, Groton, CT, 06340, United States.
authors.forename: John
authors.initials: J
authors.lastname: Marcek
authors.affiliation: Drug Safety R&D, Pfizer Worldwide R&D, Groton, CT, 06340, United States.
authors.forename: Carlin
authors.initials: C
authors.lastname: Okerberg
authors.affiliation: Drug Safety R&D, Pfizer Worldwide R&D, Groton, CT, 06340, United States.
authors.forename: Chang-Ning
authors.initials: CN
authors.lastname: Liu
authors.affiliation: Drug Safety R&D, Pfizer Worldwide R&D, Groton, CT, 06340, United States.
authors.forename: David
authors.initials: D
authors.lastname: Potter
authors.affiliation: Drug Safety R&D, Pfizer Worldwide R&D, La Jolla, CA, 92121, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Butler
authors.affiliation: Drug Safety R&D, Pfizer Worldwide R&D, Groton, CT, 06340, United States.
authors.forename: Magalie
authors.initials: M
authors.lastname: Boucher
authors.affiliation: Drug Safety R&D, Pfizer Worldwide R&D, La Jolla, CA, 92121, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Zorbas
authors.affiliation: Stereology Research Center, Inc., Tampa-St Petersburg, FL, 33741, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Mouton
authors.affiliation: Stereology and Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Department of Clinical Medicine, Aarhus University, Denmark.
authors.forename: Jens R
authors.initials: JR
authors.lastname: Nyengaard
authors.affiliation: Drug Safety R&D, Pfizer Worldwide R&D, Groton, CT, 06340, United States. Electronic address: christopher.j.somps@pfizer.com.
authors.forename: Chris
authors.initials: C
authors.lastname: Somps
keywords: Nerve growth factor; Neuron number; Neuron volume; Stereology; Sympathetic nervous system