In this review paper, literature data on pre- and postnatal eye development are compared between humans and nonclinical species that are commonly used for human safety assessment, namely, mouse, rat, rabbit, dog, minipig, and nonhuman primates. Some new data on rat and minipig ocular development are also included. This compiled information can be helpful for species selection in juvenile toxicity studies or assist in the interpretation of (non)clinical data during pediatric drug development. Despite some differences in developmental windows and anatomical peculiarities, such as the lack of a fovea centralis in nonprimate species or the presence of a nictitating membrane in some nonclinical species, the functioning and development of the eye is strikingly similar between humans and other mammals. As such, all commonly used nonclinical species appear to be relatively good models for human eye development, although some practical constraints such as size may be a limiting factor. Birth Defects Research 109:1540-1567, 2017. © 2017 Wiley Periodicals, Inc.
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Naunyn Schmiedebergs Arch Pharmacol
December 2024
Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.
J Pharmacol Toxicol Methods
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Charles River Laboratories, Mattawan, United States.
Nonclinical QTc studies can augment clinical QTc assessments in regulatory submissions provided they are of sufficient quality and sensitivity. Both the statistical performance and species translation play a role in determining the sensitivity of the model. The current analyses examine the effects of dofetilide or vehicle on the QT interval in nonhuman primate (NHP; n = 16) using a one-step estimated marginal means method where both treatment and animal ID are used in regression models to avoid a separate rate correction step, in comparison to other commonly utilized methods.
View Article and Find Full Text PDFToxicol Pathol
December 2024
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Adeno-associated virus (AAV) gene therapy vectors are an accepted platform for treating severe neurological diseases. Test article (TA)-related and procedure-related neuropathological effects following administration of AAV-based vectors are observed in the central nervous system (CNS) and peripheral nervous system (PNS). Leukocyte accumulation (mononuclear cell infiltration > inflammation) may occur in brain, spinal cord, spinal nerve roots (SNRs), sensory and autonomic ganglia, and rarely nerves.
View Article and Find Full Text PDFToxicol Sci
December 2024
Drug Safety Research & Evaluation, Takeda Development Center Americas, Inc, San Diego, CA, USA.
Seizure is among the most severe FDA black box warnings of neurotoxicity reported on drug labels. Gaining a better mechanistic understanding of off-targets causative of seizure will improve identification of potential seizure risks preclinically. In the present study, we evaluated an in vitro panel of 9 investigational (Cav2.
View Article and Find Full Text PDFThe INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions) Project (www.toxpath.org/ inhand.
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