Batten disease is a rare and fatal genetic neurological condition that affects the ability of cells to process waste materials. Those materials build up in brain cells and result in a range of symptoms including seizures, vision loss, motor and speech difficulty, slowed learning and personality changes. Eventually, children with Batten disease become blind, wheelchair-bound and bedridden, having lost all their cognitive function. Most affected children die in their early teens.

Researchers at the Oregon National Primate Research Center (ONPRC) at OHSU have discovered a naturally occurring disease in Japanese macaques that mimics the progression of Batten disease in humans. The finding holds promise for developing gene therapies to treat the disease. Human clinical trials could start within five years.

Trevor McGill, PhD, research assistant professor of ophthalmology in the OHSU School of Medicine, said the discovery will accelerate the development of new gene therapies for Batten disease.

“It affects small children and it’s fatal,” McGill said, “and we’ve got the necessary tools in hand here at OHSU to fix it.”

A multidisciplinary team of veterinarians and scientists at ONPRC made the discovery and confirmed that a small population of Japanese macaque monkeys carries a genetic mutation that causes one form of the disease. It’s the only known model for the disease among nonhuman primates in the world.

“This has truly been a collaborative effort, bringing together the expertise of clinical veterinarians and pathologists, scientists with collective expertise in primate behavior and genetics as well as brain and retinal degeneration,” said Anne Lewis, D.V.M., PhD, head of pathology at the primate center.

“The discovery of this nonhuman primate model of Batten disease will advance our ability to develop and test a gene therapy strategy to replace the normal version of the protein that is missing in this disease,” said Jodi McBride, PhD and assistant professor of neuroscience at ONPRC.

Additionally, she said, this new discovery also opens up promising avenues for developing biomarkers of the disease’s progression using advanced imaging techniques such as MRI and PET scanning.

“We don’t have great imaging biomarkers for this disease aside from the gold standard of MRI and so we’re also interested in using this new model to develop imaging techniques that will allow us to determine how successful we are at clearing out the buildup of cellular debris in the brain with potential treatments.”

The ONPRC scientists said that their goal is to quickly develop interventional strategies that can be used to help treat the children suffering from this devastating and fatal disease and offer hope to their families.

Elevated risk for diabetes and weight gain is a well-documented issue for post-menopausal women—but its biological cause isn’t as certain.

Contradicting past studies, researchers at the Wisconsin National Primate Research Center (WiNPRC) have learned that a naturally-occurring decline in one specific hormone may not be a significant factor in post-menopausal health risks, as previously thought. An article published July 19 in the International Journal of Obesity shows a much smaller role for ovarian estradiol—a steroid hormone—in female metabolism than previously thought.

In prior studies with adult female rodents, ovarian estradiol has been shown to regulate body weight, energy balance and other factors while also protecting against diet-induced obesity.

“We thought these actions also occurred in primates, but our research indicates otherwise,” said Marissa Kraynak, PhD, who co-authored the study with Ricki Colman, PhD.

To test the metabolic functions of ovarian estradiol in female nonhuman primates and discover what happens when the hormone is removed, scientists at WiNPRC selected the common marmoset monkey, which is modestly susceptible to diet-induced obesity. They studied the effects of estradiol depletion combined with diets higher in fat and sucrose, hypothesizing that this would increase body weight and decrease glucose tolerance.

“But we were surprised to see no changes in feeding behavior, activity or energy expenditure in our study monkeys,” Kraynak noted.

The study results suggest that ovarian estradiol may not be a major contributor to metabolic health in female primates. This also leaves open the intriguing possibility that estrogens produced elsewhere in the body—including the brain—may function in this capacity in both nonhuman primates and women.

Learning how the human body makes blood cells could lead to an array of off-the-shelf products for treating cancer and genetic diseases. Researchers at the University of Wisconsin-Madison School of Medicine and Public Health have used human stem cells to make blood-forming cells and demonstrated that they can function as the earliest cells from which various immune cells arise.

“It is critical to identify how nature makes blood cells and apply this knowledge as a tool to make blood cells in a culture dish,” said Igor Slukvin, professor of pathology and laboratory medicine and researcher at the Wisconsin National Primate Research Center. “These findings are important because we can now apply known pathways to improve production of pluripotent stem cells for cancer therapies.”

During embryonic development, blood cells emerge from vessels at several sites inside and outside the embryo. But the cells with the particular ability to become the type of stem cells that can produce blood cells are found only in the lining of the arteries. Using a chemical process in combination with a protein, the researchers produced an arterial type of cell that could be manipulated to create adult-type blood cells and open the way for treatments for blood cancers and other serious conditions.

Dr. Slukvin’s important research holds promise for developing an unlimited supply of blood cells for use in cancer and genetic disease therapies. Unlocking the pathway by which blood cells are created is a significant step toward longer, healthier lives for people around the world.

Dr. Nancy Haigwood, director of the Oregon National Primate Research Center, discusses the launch of nprc.org, the public-facing website of the seven National Primate Research Centers, in this podcast from Oregon Health and Science University. The website’s goal, she says, is to give the general public information about research at the NPRCs that is “helping humans live longer, healthier lives.”

Global fears about Zika virus may have waned since the disease first made headlines in 2015 – but scientists at the National Primate Research Centers continue to make important discoveries to understand and prevent its adverse effects during pregnancy.

Scientists at six NPRCs across the U.S. have recently collaborated on a study that concluded Zika may be responsible for more childbirth complications than originally thought – even when women show few symptoms during pregnancy.

The study, published in the journal Nature Medicine, showed that 26% of nonhuman primates inoculated with Zika in the early stages of pregnancy experienced miscarriage or stillbirth, despite displaying few clinical signs of infection. For scientists, this indicates that Zika-associated pregnancy loss in humans may be more common than previously believed, since the illness itself often goes undetected.

“The primary conclusion from this multi-center study with important implications for pregnant women infected with Zika virus is that stillbirth and miscarriage occur more frequently in infected nonhuman primates than animals not exposed to the virus,” explained lead author Dawn Dudley, PhD, with the Wisconsin National Primate Research Center.

This discovery matches human reports of adverse outcomes in babies exposed to Zika during the first trimester, helping to solidify the connection between Zika infection and its negative effects on pregnancy, even when symptoms are mild or absent. It also underlines the importance of frequent Zika testing for pregnant women – especially in regions where the disease has been identified.

In the U.S., infections have been reported in Florida and Texas. Now, the Texas Department of State Health Services is asking OB/GYNs in the counties bordering Mexico to test pregnant patients for Zika three times during pregnancy. In addition, all pregnant women across the country are cautioned to protect themselves against mosquito bites.

Researchers from the seven National Primate Research Centers have joined six Nobel Laureates and a growing contingent of America’s scientific community in signing a letter that acknowledges the importance of animal research as well as transparency. The letter calls upon “our country’s research institutions – large and small – to embrace openness. We should proudly explain how animals are used for the advancement of science and medicine, in the interest of the health and wellbeing of humans and animals.”

“We fully support the goal of helping the public understand and trust the research process,” says John Morrison, PhD, director of the California National Primate Research Center. “All seven NPRCs engage in community and educational outreach to provide information about our research as well as the care of our animals.”

USA Today printed the letter and signatures June 20.

The holy grail of autism research is a reliable test for the condition – and researchers at the California National Primate Research Center (CNPRC), working with colleagues at the Stanford University School of Medicine, have made a promising discovery that may lead to just such a test.

According to the research team, reduced levels of vasopressin – a hormone found in the spinal fluid – may be connected to a reduction in socially acceptable behavior.

“What we consider this to be at this point is a biomarker for low sociability,” said John P. Capitanio, a CNPRC scientist and leader of the Neuroscience and Behavior Unit at the University of California-Davis.

Currently, medical professionals diagnose autism by looking for certain social behaviors. Unfortunately, these tell-tale signs often don’t appear until a child reaches age four or five, limiting opportunities for early treatments that can stem the condition’s progress.

“Right now, the diagnosis is based on parents’ reports of their children’s symptoms, and on clinicians observing children in the clinic,” said Karen Parker, associate professor of psychiatry and behavioral sciences at Stanford and the lead author of the new study.

Researchers looked for autism biomarkers in rhesus macaques, a species whose social capabilities are close to those of humans. The scientists measured levels of two hormones, oxytocin and vasopressin, in their blood and in their cerebrospinal fluid, which bathes the brain.

Monkeys in the less social group had significantly less vasopressin in their cerebrospinal fluid than nonhuman primates in the more social group. In particular, the levels accurately predicted the frequency with which individuals participated in social grooming, an important social activity for this species. Importantly, the team was able to replicate their finding that low vasopressin levels are associated with lower social functioning using a second, independent cohort of monkeys.

The researchers also compared vasopressin levels in seven boys with autism and seven others without the condition. Similar to the results with the rhesus macaques, children with autism had lower vasopressin levels than children without autism.

Moving forward, the researchers plan to test a larger group of nonhuman primates to determine whether the low hormone level can be detected before symptoms of impaired social ability emerge.

Reviewed August 2019

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

The effects of Zika on an adult are upsetting enough, but the impact it can have on unborn children and newborns is heart wrenching, which is why researchers at the Yerkes National Primate Research Center have made studying Zika virus a priority.

One of the most common consequences of Zika infecting an unborn child is microcephaly – a birth defect that leaves the baby with an unusually small head and undersized brain. It can be fatal, and infants who survive usually face intellectual disabilities and developmental delays.

When researchers at the Yerkes National Primate Research Center in collaboration with colleagues at Emory University School of Medicine and Children’s Healthcare of Atlanta wondered whether contracting the disease early after birth had the same effect, they noted some small, but important distinctions. For example, the disease did not appear to affect vision or visual memory.

“This gives us hope that in our future work, we can find ways to limit Zika’s effect on the developing brain,” said Ann Chahroudi, MD, PhD, the study’s lead researcher.

For now, because there is lasting damage to the nervous system and areas of the brain, the research team recommends more than just routine monitoring for pediatric patients known to be infected with Zika.

The researchers hope further work with the monkey model will allow them to study in more detail the effects of postnatal Zika virus infection on the brain and give them opportunities to test therapies for alleviating or even preventing the neurologic consequences of Zika virus infection.

Concerns about antibiotic-resistant bacteria have been growing in recent years, and researchers at the Yerkes National Primate Research Center (YNPRC) have added another to the list. Klebsiella pneumoniae, a bacterium that causes blood, soft tissue and urinary tract infections, has been found resistant to colistin, a powerful last resort antibiotic. In 2013, the Centers for Disease Control and Prevention (CDC) listed Carbapenem-resistant Enterobacteriaceae (CRE), which include Klebsiella, as one of the top three urgent antibiotic resistant threats.

According to the CDC, healthy people usually don’t contract this type of infection. It usually affects patients in hospitals, nursing homes and other health-care settings. Patients whose care requires devices such as ventilators, urinary catheters or intravenous catheters, and patients who are taking antibiotics for a long period of time are most at risk for CRE infections. Various types of Klebsiella are estimated to be responsible for 10 percent of infections acquired in health-care facilities.

“This is concerning because Klebsiella is a more common cause of infection than Enterobacter,” said David Weiss, a researcher at the Yerkes National Primate Research Center and the director of the Emory Antibiotic Resistance Center. “To our knowledge, this type of [antibiotic-resistant] Klebsiella has not been observed in the United States before.”

Despite the extra time required, Dr. Weiss and his colleagues recommend clinical laboratories consider testing for heteroresistance to colistin if this last line antibiotic is required for CRE treatment.

Want to live longer? Eat less.  

That was the finding of a previous study by researchers at the Wisconsin National Primate Research Center (WiNPRC). And now, those same researchers may have discovered why.

“We knew that restricting calories helps monkeys to live longer, healthier lives, but we did not understand the basis for this extraordinary finding,” said Rozalyn Anderson, a professor and medicine and one of the study’s authors. Anderson worked closely with WiNPRC’s Dr. Ricki Colman, whose colony of rhesus monkeys was studied. “We are now at the beginning of a very exciting journey to discover how calorie restriction works on the molecular level.” Colman is a WiNPRC senior scientist and assistant professor at the University of Wisconsin-Madison.

Two groups of rhesus monkeys were studied for two years – one fed a normal diet while the other ate a diet with 30 percent fewer calories. The research team focused on the liver, because that is where nutrients are processed, and because it plays a key role in metabolic health. Through their research, the team catalogued more than 20,000 molecules in the rhesus liver and analyzed the data.

What the researchers found is that the lower calorie diet changed the way the liver was working, including how it metabolized proteins, carbohydrates, and lipids. Most surprising? The fact that calorie restriction was changing the metabolism on a genetic level using RNA processing.

“Although for some it will not be a surprise that metabolism is important to how calorie restriction works, we are talking about a dietary intervention after all,” said Anderson. “What is more interesting is the recent work showing profound metabolic effects in a whole host of age-associated diseases that are otherwise unrelated. We think that the metabolic response to calorie restriction is at the very heart of its ability to delay aging and the onset of age-related disease.”

While the implications of this discovery are still forthcoming, it’s certainly significant. In the meantime, keep on living, breathing, and eating – just not too much eating.

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