New federal funding will enable investigators at the Oregon National Primate Research Center to generate and store embryos of nonhuman primates for use by researchers across the country to better understand and develop treatments for diseases affecting both people and monkeys.
Oregon Health & Science University, which operates the primate center, will use the $2.7 million, four-year award from the National Institutes of Health to establish a first-of-its-kind resource to preserve gametes, embryos and fibroblast cellular tissue from nonhuman primate models of human disease. Gametes are mature male or female germ cells that unite to form a zygote.
“It’s going to allow researchers to have access in a way we’ve never had before, while also reducing the number of animals needed to maintain these incredibly valuable disease models,” said Larry Sherman, Ph.D., professor in the Division of Neuroscience at the primate center.
The project will for the first time enable scientists to maximize the availability of an exceptionally valuable resource: nonhuman primates that carry spontaneously occurring genetic mutations that cause medical conditions, closely paralleling human disease. Thousands of rhesus macaque monkeys at the Oregon primate center have had their genomes sequenced and stored in a genetic database known as mGAP.
The database enables scientists to study a wide array of naturally occurring conditions in nonhuman primates, making them ideal models for developing therapies that are ultimately applied to people.
“Some of these diseases are incredibly rare,” Sherman said.
For example, Sherman is studying a neurodegenerative disease recently discovered in a few rhesus macaques at the primate center. He is also studying models of Batten disease and multiple sclerosis, which have also been detected in macaques at the primate center. Caring for those animals and their offspring requires a substantial dedication of resources, in some cases years before scientists studying any particular disease are ready to apply potential therapies to monkeys. This gap is made even more acute in light of a global shortage of research animals.
“Nonhuman primate work is expensive, and it’s much harder to get animals now,” said Carrie Hanna, Ph.D., director of the Assisted Reproductive Technology core at the primate center.
Generating and freezing embryos helps to bridge that gap, reducing the number of animals needed to maintain each disease model.
Scientists will generate embryos through in vitro fertilization, using eggs and sperm provided by research animals known to carry gene mutations.
“It works like a bank,” Sherman said. “Say you’re a researcher interested in Tay-Sachs disease, and you have this great idea for a therapy that works in a mouse. You could go to mGAP and try to find an animal with this specific mutation and make embryos for that.”
Embryos can be held in Oregon, or transported to centers capable of implanting the embryos to establish pregnancies in research animals when investigators are ready to study a specific disease model. The Oregon primate center also will provide training and support for veterinary staff at five other national primate research centers for the collection of gametes.
The NIH awarded the grant to OHSU’s Oregon National Primate Research Center because it has established and maintained a strong assisted reproductive technology core, Hanna said.
“We have one of the most robust programs among primate centers,” she said.
And, Hanna said, thousands of embryos can be stored at the center.
“It’s setting up a future for continuing research after the life of this grant,” she said. “We can store these embryos indefinitely.”
All research involving animal subjects at OHSU must be reviewed and approved by the university’s Institutional Animal Care and Use Committee (IACUC). The IACUC’s priority is to ensure the health and safety of animal research subjects. The IACUC also reviews procedures to ensure the health and safety of the people who work with the animals. The IACUC conducts a rigorous review of all animal research proposals to ensure they demonstrate scientific value and justify the use of live animals.