The rapid spread of the Zika virus has led to widespread media and government attention; however, little is known about the disease itself. How long does the disease stay in the system? Where does the Zika virus attack? And how does it spread to offspring?

A team of interdisciplinary researchers from OHSU in Portland, Oregon, is attempting to find these answers. Collaborating with the Oregon National Primate Center (ONPRC), the team is beginning to unlock the mysteries of the virus – and ultimately pave the way for future therapies and vaccines.

“This study helps us better understand how the virus manifests itself so that scientists can develop therapies and vaccines that would work in humans,” says Dr. Daniel Streblow, Associate Professor of Molecular Microbiology and Immunology in the OHSU Vaccine and Gene Therapy Institute, OHSU School of Medicine. “Our study significantly advances what is known about the growth of the virus in the host.”

The research team, a 20-person cross-section of faculty across the university, examined the Zika virus infection in seven rhesus macaques from March 2016 to August 2016. The study observed the Zika virus at seven, 28 and 35 days post-infection.

Ultimately, it was found that the Zika virus attacks tissues in the nervous system, male and female reproductive and urinary tracts, muscles, joints and lymph nodes. The virus first presents itself as a rash, fever or pink eye, and then persists in the body for at least 35 days.

“What is different about this research is that we also were able to look at specific points in time to see where the virus grew in the tissues so we can identify and target the reservoirs where the virus hides,” says Dr. Streblow.

This medical study was conducted in response to the Zika virus outbreak across the Western hemisphere. In 2016, there were 5,102 reported cases of the Zika virus in the United States, and an additional 36,079 cases reported in US territories.

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Photo credit: Kathy West for the California National Primate Research Center

The controversy is over. Consuming fewer calories leads to a longer, healthier life, according to a joint report from the Wisconsin National Primate Research Center and the National Institute of Aging (NIA) on the diets of rhesus monkeys.

This report is the third in a series researching the effect of caloric intake on aging. In 2009, the UW–Madison team, led by primate center scientist Dr. Ricki Colman, reported that rhesus monkeys that ate less had fewer instances of cancer, cardiovascular disease, and insulin resistance. However, a 2012 study from the NIA showed no significant correlation between diet and health. With both teams hungry for an answer, they worked together to reach a more satisfying conclusion.

“These conflicting outcomes had cast a shadow of doubt on the translatability of the calorie restriction paradigm to understand aging and what creates age-related disease vulnerability,” said Rozalyn Anderson, an associate professor of medicine at UW–Madison collaborating with Dr. Colman and others on the study.

After comparing the two independent reports, the research team drew four key conclusions.

• Eating less is more beneficial for adult and older primates than for younger or juvenile animals.
• The number of calories reduced matters. The test group at UW–Madison ate less than the group at NIA and was less at risk for major health issues.
• Less processed food leads to fewer health issues. The NIA primates ate naturally sourced foods compared to the high-fat, sugar-rich diet of those at UW – Madison.
• Comparatively, females are less affected by a fatty diet.

While the two original studies considered caloric intake, they didn’t factor in the effect of age, diet, and sex. It’s those other ingredients, when evaluated alongside calorie count, that make up the complete recipe for healthy living. Energized by this discovery, researchers continue to explore the interaction between calorie count and quality of life.

Reviewed August 2019

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Photo credit: Yerkes National Primate Research Center

Imagine a day where we’re able to treat some of the world’s most debilitating neurological disorders, like Parkinson’s, strokes and brain injuries. While this day may seem far removed, scientists at the Southwest National Primate Research Center (SNPRC) are taking steps toward making the dream a reality.

Dr. Marcel Daadi of SNPRC is developing a more effective method for delivering neural stem cells to the brain in an effort to move forward stem cell therapies to treat neurological disorders. His research has already developed stem cells capable of becoming the type of cells Parkinson’s patients lose over time, or dopaminergic cells. An MRI-guided technique to implant these cells would move scientists one step closer to delivery of this therapy to patients.

“Stem cell-based therapy is emerging as a promising treatment for a variety of diseases and injuries. The first step in evaluating the potential of different therapeutic stem cell lines is to develop a safe and effectively reproducible delivery system,” Dr. Daadi explained.

Injection parameters have been well studied in drug delivery methods; however, they simply cannot be directly applied to stem cell-based therapy and the technology for stem cell delivery is undeveloped and limited.

Dr. Daadi and his colleagues developed an operational technique for delivering stem cells with low invasiveness and high accuracy in placement of the stem cells to the basal ganglia part of the brain. The basal ganglia controls motor skills compromised in Parkinsons disease.

The team tested the technique on baboons at SNPRC and not only showed effective targeted delivery but also revealed the cells were not released at a steady rate but instead dispersed in small bursts. This is a significant finding as it demonstrated how injected cells disperse in the host brain and stimulates new ideas on how we can prepare the cells to function at their best.

“We wouldn’t have been able to see this phenomenon using standard stereotaxic delivery,” Dr. Daadi said. “With iMRI, we can visualize in real time the cells being injected to the target area. A non-invasive MRI approach is becoming a necessity in clinical applications to enhance the safety of patients and the efficacy of the therapeutic approach. We can create the best cells, but if we can’t transplant them to the patient in a consistent and predictable way so that the patient can accept and thrive from them, then the therapy is simply ineffective.”

Only one individual in history has been cured of HIV. This person is known as “the Berlin patient,” named for the location where the renowned HIV-ridding procedure took place. Scientists at the Oregon National Primate Research Center (ONPRC) at OHSU are working to understand how a specific mutation in a gene may block HIV infection in the host. Using CRISPR technology, researchers are creating the same mutation and bone marrow transplantation performed on that patient to study how it might play a role in HIV infectivity.

Jon Hennebold, professor and chief, Division of Reproductive & Developmental Sciences, at ONPRC, said that Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR) genome-editing technology is responsible for these new insights. “You can’t fully study HIV in rodent models because it’s a primate-tropic virus,” he said. CRISPR is essentially a programmable molecular scissors that scientists can manipulate to edit the genes within organisms. CRISPR/Cas9 seeks and targets specific genes in organisms that are linked to diseases by utilizing a single strand of RNA as a guide to target specific genes for editing.

“This technique exploded in the scientific community about five years ago, so it’s relatively new,” Hennebold said. “Basically, CRISPR works by cutting the DNA in the target gene of interest, which in turn results in the creation of a mutation at that site when the cell repairs the gap in the gene,” Hennebold said. “It doesn’t do it randomly. It goes to a gene of interest and will cut the DNA at that point.” Further, “It was a huge advance from the standpoint of being able to modify genomes, so it could be used to modify many different organisms’ genomes. Previously, you were only able to do that in a few models. You could never apply the previous approaches to organisms other than mice.”

In addition to work with HIV, CRISPR is currently being used to help researchers understand conditions such as blindness, autism, and neurodegenerative diseases that are too complex to be studied in a rodent research model.

Menopause isn’t always accompanied by physical symptoms. In fact, for many women, the side effects of this hormonal change aren’t quite as tangible as hot flashes and stiff joints. A decline in mental faculties such as reasoning and perception can often occur. However, a study from the Oregon National Primate Research Center suggests that hormone therapy may mitigate such cognitive changes.

For the nonhuman primates treated with estradiol implants, both spatial working memory and visuospatial attention improved throughout the course of the one-year testing period compared to those receiving a placebo. While post-menopausal hormone therapy has been a frequent topic of debate, the research supported the hypothesis that estradiol treatment is a sustainable solution for managing symptoms.

“There have been several previous studies published on the effect of hormone therapy on cognition in the nonhuman primate, with equivocal results,” said lead author Dr. Steven G. Kohama, a neuroscientist at the Oregon NPRC. “However, in comparison to these earlier reports, our study was much longer, and it suggests a sustained benefit from early intervention after menopause with hormone treatment.”

As the pro-hormone therapy argument grows stronger, the list of research questions grows longer. Researchers are already considering whether treatment earlier in menopause slows cognitive decline more than therapy introduced later.

14 million – that’s how many women in the United States suffer from Polycystic Ovary Syndrome (PCOS), a crippling disease that that increases  risk of endometrial cancer, heart disease, high blood pressure, type 2 diabetes, asthma, obesity, depression and anxiety. Women with PCOS also experience infertility and a variety of reproductive disorders, resulting in heartbreak for millions of American families.

“With so many different symptoms, it took a long time for physicians to identify the disease as more than infertility,” explains Dr. David Abbott, professor of OB/GYN at the University of Wisconsin-Madison School of Medicine and Public Health who has studied the origins of PCOS at the Wisconsin National Primate Research Center for nearly 30 years.

Yet, despite its widespread reach, PCOS has long stumped scientists. That’s why researchers from the California and Wisconsin National Primate Research Centers, Northwestern University Feinberg School of Medicine and University of California-Los Angeles combined forces to search for causes, preventions, treatments and cures for PCOS.

Each scientist’s decades of experience and research came together in a comprehensive review of 114 articles reporting different PCOS biomarkers. The review also covers overall progress in improving the lives of PCOS patients, including better counseling, managed care and new directions in genetic testing.

For example, a recent study from the Wisconsin NPRC examines testosterone levels in the hair of newborn monkeys. The results reveal that, while PCOS symptoms may not appear until puberty, the disease might actually be programmed in the fetus during the second trimester of pregnancy. Such tests in human infants will allow medical professionals to identify and ameliorate PCOS before onset. Knowledge of its genetic origins and that PCOS may be programmed during intrauterine life allows scientists to explore how the maternal-fetal environment affects female health over generations.

Even after 30 years of continuous research, scientists like David Abbott anticipate much more discovery in the field of PCOS. He notes that, “today, thanks to researchers and doctors working together on all aspects of this problem, many more clinicians cross-refer to one another, and catch more of the specific pathologies that can lead to a PCOS diagnosis and better care.

Reviewed August 2019

The West African outbreak of Ebola virus in 2014 made Ebola a household word. The outbreak made clear that infectious diseases know no borders and have global impact.

Ebola first emerged 40 years ago, spreading its deadly symptoms across South Sudan and the Democratic Republic of Congo. According to the World Health Organization, Ebola has a 50% average mortality rate. During the 2014-2016 outbreak, the disease infected over 28,000 people in West Africa and killed over 11,000. Currently, there are no FDA-approved treatments or vaccines for the Ebola virus – but the team at Texas Biomedical Research Institute and the Southwest National Primate Research Center is working to change that.

These scientists are working with the National Institutes of Health, the Biomedical Advanced Research and Development Authority (BARDA) and the Department of Defense to develop assays and evaluate vaccine and therapeutic candidates.

Most recently, a group of Texas Biomed scientists led by Dr. Ricardo Carrion and Dr. Anthony Griffiths was awarded a $6.6 million contract in November 2017 from the Biomedical Advanced Research and Development Authority (BARDA) to test a drug cocktail for efficacy against Ebola virus disease. These well-regulated, controlled studies that will begin in 2018 are a critical next step before declaring this drug cocktail safe and effective in humans.

“Texas Biomed is the only Institute of its kind in the country, with two extraordinary resources in one place – the BioSafety Level – 4 (BSL-4) facilities and nonhuman primate colonies,” said Scientist and Director of Texas Biomed’s BSL-4 laboratory Dr. Robert Davey.

In 2015, after discovering that tetrandrine works to stop the Ebola virus, Dr. Davey and his lab wondered: how can we move this herbal remedy into the clinic?

He has since teamed up with scientists at the Southwest Research Institute (SwRI) to develop a synthetic route to make safer versions of tetrandrine with better clinical properties as potential therapeutics against the virus. To support their scientific studies, the team of researchers received an NIH research and development contract worth up to $4.1 million.

From helping diagnose a disease to curing them, scientists at Texas Biomed and the Southwest National Primate Research Center continue the fight against pathogenic invaders and the search for new ways to approach global health threats.

Since the early 1990s, a team at Yerkes National Primate Research Center has been developing and refining a costimulation blocker that will prevent the immune system from rejecting transplanted organs. The Food and Drug Administration approved the drug, belatacept, or Nulojix as it’s commonly known, in 2011 for kidney transplants. Ever since, the team has been working to expand the applications of this research to other organs.

As a result of the research team’s success, the National Institute of Allergy and Infectious Disease awarded it a $12.6 million grant to continue these efforts.

“Our research is aimed at extending the benefits of costimulation blocker-based regimens to a larger group of transplant patients, and helping them to have longer, healthier lives,” says Christian Larsen, a Yerkes researcher and professor of surgery at Emory University School of Medicine.

The team’s newest line of research has identified biomarkers on immune cells that may predict whether or not immune cells that are resistant to belatacept will reject the transplant. To determine the predictive ability of these biomarkers, the team will continue working with the nonhuman primates at the Yerkes Research Center.

In addition, researchers will be investigating possible solutions for targeting those costimulation blocker-resistant cells and strategies for preserving the immunity of the organs post-transplant. Such research is key for helping people who have organ transplants live a normal life span.

Reviewed August 2019

Are vaccines tied to an increased risk of autism? That’s the question researchers at the Washington National Primate Research Center (WaNPRC) are working to answer. While scientific research continues, the results of a recent study shows no obvious connection between following a vaccination schedule and brain defects.

The study focused on vaccines containing thimerosal, a chemical designed to protect the vaccine from bacterial contamination. This mercury-based compound, after decades of use, has largely been phased out at the recommendation of the Food and Drug Administration because of fears about an overexposure to mercury. However, flu and meningitis vaccines continue to use thimerosal.

“It is of great importance to determine whether childhood vaccines that contain this preservative play a significant role in altering brain development, such as autism,” said lead investigator Dr. Laura Hewitson of The Johnson Center for Child Health and Development and affiliate investigator with the WaNPRC.

Using a nonhuman primate model, the study showed no negative side effects such as rocking, self-clasping, or other repetitive behaviors after exposure to thimerosal-containing vaccines. In addition, research didn’t identify any noticeable neurochemical distinctions between vaccinated and unvaccinated test models.

This discovery is good news for advocates of childhood vaccinations, and by connection, for millions of kids  who receive vaccines each year. However, until there is a definite answer, the National Primate Research Centers will continue this research.

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Photo credit: Kathy West for the California National Primate Research Center

An estimated 15.1 million adults in the United States have Alcohol Use Disorder (AUD), a chronic brain disease characterized by compulsive alcohol use. This includes approximately 6.2 percent of all American adults, a staggering percentage of drinkers nationwide.

“The amount of alcohol consumed in the US is not only substantial, but unequally divided in terms of who drinks how much,” said Dr. Kathleen Grant, Chief and Senior Scientist of Behavioral Neuroscience at the Oregon National Primate Research Center (ONPRC). “A small proportion drink the vast majority of alcohol sold.”

But why can some people safely enjoy a single nightcap, while others are at risk for developing alcoholism or a serious alcohol problem?

Dr. Grant hopes to answer that very question by studying a population of rhesus monkeys. Through her research, she is unraveling why some people are at a greater risk for heavy drinking habits.

Dr. Grant studies monkeys who have been exposed to alcohol over the course of three months. Like humans, some choose to drink water, some choose to drink alcohol, and some choose to drink a combination of the two. Understanding why certain monkeys choose to drink alcohol heavily provides clues as to why some humans are at a higher risk for developing a drinking problem.

Dr. Grant has found that males – both monkeys and humans – are more likely to become problem alcohol drinkers than females. In addition, monkeys that are exposed to stressful situations or stimuli choose to drink alcohol more than those that are not.

However, there are several risk factors that affect humans, but are not seen in monkeys. For example, in humans, family history of alcoholism can affect one’s inherited genes and environment and ultimately lead to an increased risk of heavy drinking. In addition, drinking alcohol between the ages of 13-15 increases the lifetime chances of being diagnosed with alcohol dependence.

Ultimately, Dr. Grant hopes her research will help identify those at risk for developing alcoholism before they’ve developed an alcohol addiction. By determining certain biomarkers in the brain and blood, she is hopeful that, eventually, we can caution people that they’re heading toward addiction before it begins.

“Prevention would be so much better for everyone because alcoholism affects more than just the individual,” Dr. Grant said.

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Photo credit: Kathy West for the California National Primate Research Center