This application aims to develop a highly novel non-human primate (NHP) resource for investigators performing pre-clinical studies in three neurodegenerative diseases that affect humans: multiple sclerosis (MS), Batten disease, and age-related macular degeneration (AMD). Subpopulations of Japanese macaques (JMs) housed at the Oregon National Primate Research Center (ONPRC) spontaneously develop conditions that mimic each of these diseases. Japanese macaque encephalomyelitis (JME) shares many of the pathophysiological features of multiple sclerosis (MS) in humans including demyelination and axonal damage linked to nervous system attacks by myelin-reactive immune cells. Japanese macaque Batten disease (JMBD) is genetically and pathophysiologically similar to a form of human neuronal ceroid lipofuscinosis (CLN7) that causes vision loss, motor dysfunction and other neurological symptoms. Japanese macaque dominant drusen (JMDD) is a model of human AMD, which is the leading cause of vision loss among people over the age of 50. At present, there are limited or no treatments for any of the human forms of these diseases, making these NHP models extraordinarily valuable to the research community. Ongoing studies in each of these NHP disease models have demonstrated that specific groups of animals within the colony or animals with specific genotypes are pre-disposed to each of these conditions. As a result, it is possible to generate animals that develop each disease through targeted breeding, providing a unique opportunity to generate a resource for investigators focused on studying mechanisms of disease onset and progression, or who are developing strategies to treat each disease. We therefore aim to: (1) develop targeted breeding colonies of JME, JMBD, and JMDD animals; and (2) develop a bank of tissues from unaffected JMs and animals with JME, JMBD, and JMDD. All together, this proposal will develop a novel resource that will provide investigators interested in MS, Batten disease, or AMD with access to animals and tissues to support pre-clinical studies aimed at delaying, halting or reversing disease progression.

Public Health Relevance

Non-human primate models of neurodegenerative diseases provide valuable platforms for testing the safety and efficacy of novel strategies to prevent, delay, or reverse disease pathophysiology. The colony of Japanese macaques at the Oregon National Primate Research Center spontaneously develop three neurological diseases that are similar to conditions that afflict millions of patients each year: multiple sclerosis, Batten disease, and age-related macular degeneration. The goal of this project is to develop this colony into a resource for investigators studying each of these diseases and ways to treat them.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Resource-Related Research Projects (R24)
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Special Emphasis Panel (ZNS1)
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Morris, Jill A
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Oregon Health and Science University
Internal Medicine/Medicine
Schools of Medicine
United States
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McBride, Jodi L; Neuringer, Martha; Ferguson, Betsy et al. (2018) Discovery of a CLN7 model of Batten disease in non-human primates. Neurobiol Dis 119:65-78