Researchers at the Wisconsin National Primate Research Center (WiNPRC) at the University of Wisconsin-Madison (UW) recently made a discovery that moves the scientific community one step closer to understanding and treating Parkinson’s disease. 

Parkinson’s, which affects more than 10 million people worldwide, progressively degrades the nervous system, causing tremors, loss of muscle control, cardiac and gastrointestinal dysfunction and other issues. The group at WiNPRC used gene-editing tools to introduce the disease’s most common genetic mutation into marmoset monkey stem cells and successfully reduce flaws in cellular chemistry. 

“We know now how to insert a single mutation, a point mutation, into the marmoset stem cell,” said Marina Emborg, professor of medical physics at UW. “This is an exquisite model of Parkinson’s. For testing therapies, this is the perfect platform.” 

The researchers used a version of the gene-editing technology CRISPR to change a single nucleotide—among more than 2.8 billion pairs—in the genetic code of the cells and give them a mutation called G2019S. 

In human Parkinson’s patients, G2019S causes over-activity of an enzyme called LRRK2, which is involved in a cell’s metabolism. Other gene-editing studies have seen cells produce both normal and mutated enzymes at the same time.  

This new study, however, is the first to result in cells that make only enzymes with the G2019S mutation, which makes it easier to study what role this mutation plays in the disease. 

“The metabolism inside our stem cells with the mutation was not as efficient as a normal cell, just as we see in Parkinson’s,” said Emborg. “Our cells had a shorter life in a dish. And when they were exposed to oxidative stress, they were less resilient to that.” 

The mutated cells had shorter life and were less resilient to oxidative stress. They also showed lackluster connections to other cells. Stem cells can develop into many different types of cells found throughout the body. But when the researchers spurred the mutated stem cells to differentiate into neurons, they developed fewer branches to connect and communicate with neighboring neurons. 

“We can see the impact of these mutations on the cells in the dish, and that gives us a glimpse of what we could see if we used the same genetic principles to introduce the mutation into a marmoset,” says Jenna Kropp Schmidt, a WiNPRC scientist and co-author of the study.  

The researchers also used marmoset stem cells to test a genetic treatment for Parkinson’s. They shortened part of a gene to block LRRK2 production, which made positive changes in cellular metabolism. 

“We found no differences in viability between (the altered cells) and normal cells, which is a big thing. And when we made neurons from these cells, we actually found an increased number of branches,” Emborg says. “This (particular technique) is a good candidate to explore as a potential Parkinson’s therapy.” 

To learn more about how scientists across the NPRC network are combating Parkinson’s disease and other neurological disorders, visit this link. 

Cardiovascular disease is one of the leading causes of death in the United States, and it has many possible causes. One of the most well-known risk factors is hyperlipidemia, which presents as a high level of lipids, like triglycerides or cholesterol, in the blood. Scientists and doctors are still looking for effective ways to reduce cardiovascular risk from hyperlipidemia—and according to new research, fish oil may be part of the solution.

Recently, a team including Peter Havel, DVM, PhD, of UC Davis and the California National Primate Research Center (CNPRC) found that targeting a protein known as angiopoietin-like protein-3 (or ANGPTL3) could be helpful for managing cardiovascular disease.

In the study, the scientists gave 59 male rhesus macaques flavored, fructose-sweetened beverages daily in addition to their regular diet. A subset of macaques also received a whole fish oil supplement. The fructose supplementation allowed researchers to model symptoms of metabolic syndromes seen in humans, including insulin resistance and hyperlipidemia. This model also rapidly increased levels of triglycerides and certain lipoproteins in the blood, mirroring human risk factors for cardiovascular disease.

The results showed ANGPTL3 levels increased simultaneously with lipid levels in monkeys fed a high-sugar diet. It was also found that inhibiting the production of ANGPTL3 resulted in lower levels of several lipids and lipoproteins in circulation, which suggests the protein could be a helpful therapeutic target. What’s more, the researchers found that increases in the protein and lipids in the blood could be prevented if the animals were also provided with the fish oil supplement.

While the exact mechanisms remain unknown, Havel hopes to clarify in future studies exactly how components of fish oil influence ANGPTL3 production and circulating lipid levels. Understanding this could help scientists develop new interventions for the prevention and treatment of cardiovascular disease.

Heart health is incredibly important, which is why NPRC scientists are actively conducting research on cardiovascular diseases and treatments. Learn more about their breakthrough discoveries by visiting this link.

The seven National Primate Research Centers (NPRCs) are participating in SciFest All Access 2020. This is the virtual answer to the postponed USA Science & Engineering Festival, which is recognized as the nation’s top science and engineering festival for K-12 students, college students, educators and families. Happening now through Oct. 3, registered participants can visit the NPRCs in the “Exhibit Portal, Health & Medicine Zone II.”

The NPRC booth includes links to NPRC.org, our collective website, as well as individual web pages for the seven centers. All pages are filled with educational resources and links to help you learn more about our research, the scientific advancements we’re making and the care we provide our research animals. Direct access links to these seven pages are provided below.

NPRC representatives will be “on site” at SciFest All Access answering questions registered participants submit via the “Ask a Question” link in the booth. We’re also answering questions participants email us at nprcoutreach@gmail.com.

You can learn even more about the NPRCs’ research to improve human and animal health by visiting NPRC.org and following us on Twitter at @NPRCnews.

We look forward to joining thousands of students, educators and families at this year’s SciFest All Access!

SciFest All Access NPRC Web Pages

California NPRC

Oregon NPRC

Southwest NPRC

Tulane NPRC

Washington NPRC

Wisconsin NPRC

Yerkes NPRC

When fighting cancer, patients need every advantage possible, and new research results have shown a potential breakthrough that could help protect the health of those undergoing chemotherapy.

Scientists at the Wisconsin National Primate Research Center (WiNPRC) at the University of Wisconsin–Madison (UW) have developed a more efficient way to grow white blood cells, which serve as front-line defenders against bacterial infections but are often depleted during cancer treatment. Chemotherapy can leave cancer patients with a very low number of a specific type of white blood cell called neutrophils. This can result in febrile neutropenia, a dangerous condition marked by fever and heightened risk of infection.

This condition is usually treated with a transfusion of the white blood cells from a donor. But collecting enough neutrophils for transfusion is difficult, according to Igor Slukvin, MD, PhD, professor of pathology and laboratory medicine at the UW School of Medicine and Public Health, and the transfusions don’t always show the intended benefit in controlled trials.

“The complicated logistics of granulocyte collection, the need for pre-treating donors with G-CSF (a treatment that stimulates bone marrow to produce granulocytes) or steroids, difficulties in collecting a sufficient number of good quality granulocytes and the limited storage time of around 24 hours all hamper the utility of granulocyte transfusion for correcting neutropenia and may contribute to the inconclusive results observed in clinical trials,” he said.

Now, Sluvkin and a team of researchers have developed a method to generate neutrophils for weeks on end using stem cells. This solution replaces the standard, expensive, relatively inefficient and time-intensive process for neutrophil production.

Using modified messenger RNA, the technique sparks the production of a specific protein that guides the stem cells through a developmental process to become a sheet of hemogenic endothelium (found in blood vessels), which then begins producing neutrophils. These white blood cells can eventually be collected and administered to patients without some of the risk caused by other blood products often carried along in transfusions.

This technique produces neutrophils in as soon as 14 days, compared to as much as a month in previous studies, and can generate up to 17 million neutrophils from one million human induced pluripotent stem cells.

Notably, the scientists learned the neutrophils generated using this method are functionally similar to peripheral blood neutrophils and can phagocytize (surround and swallow) and kill bacteria.

These neutrophils also create opportunities to study other diseases, since white blood cells produced from stem cells carrying genetic disorders that weaken or otherwise affect the neutrophils will still retain those problems. The new production method could give researchers a ready source of malfunctioning cells and enable observation in the earliest stages of development.

The NPRCs are conducting stem cell studies at our locations across the nation. See more ways we’re applying this research to help solve a variety of health issues.

The Wisconsin National Primate Research Center (WiNPRC) has launched the newly improved Primate Info Net (PIN). The website provides resources for anyone interested in nonhuman primates.

Some of PIN’s most prominent features include primates in the news, educational resources, such as the always popular primate species fact sheets, informational services and research resources. Whether looking for a few nonhuman primate facts or more detailed information, PIN can provide the guidance you need.

Other features on the improved site include Ask Primate and the Career Center. Ask Primate allows anyone to inquire about any primate or primatology topic. The Career Center facilitates exploration of jobs and volunteer opportunities in primatology, as well as career guidance from scientists.

“We hope the relaunch of PIN will make learning about primates an enjoyable and informative experience,” says Jordana Lenon, Senior Editor, at WiNPRC. “We encourage you to explore the new PIN and to contact us with any questions about this updated resource. We hope you’re as excited as we are about PIN’s return!”

It may seem counterintuitive, but could cutting back on calories help us preserve the body’s capabilities as we age?

According to new research from the Wisconsin National Primate Research Center (WiNPRC) at the University of Wisconsin (UW) School of Medicine and Public Health, monkeys on calorie-restricted diets age better than monkeys on a normal diet.

This is the latest in a series of papers from the Aging and Calorie Restriction Study based at WiNPRC. The series first garnered attention 10 years ago, when the improved survival and health benefits of calorie restriction were initially reported.

In the latest study, there were two groups of aged rhesus monkeys—one on a normal diet and another on a fully nutritionally complete diet with 30 percent fewer calories.

The scientists found that muscle mass was up to 20 percent better preserved in the calorie-restricted monkeys, and muscle quality also improved. These benefits were linked to better muscle function, more efficient movement and better diabetes risk profiles like blood glucose levels and insulin sensitivity.

“It’s all about metabolism,” said Associate Scientist Timothy Rhoads, PhD. “Not just in the muscle tissues themselves, but more broadly at the systemic level, too”.

Associate Professor of Medicine Rozalyn Anderson echoed his sentiments.

“Calorie restriction (CR) preserves muscle quality and physical function in monkeys, and our work connects this specifically to metabolism—how energy is derived, stored and used,” she said.

Researchers at the NPRCs across the country are helping to demystify the aging process. For additional reading, check out this recent study from the California National Primate Research Center (CNPRC), which examined the changing social habits of aging primates.

Protecting against three diseases at once may seem improbable, but a recent study has produced a vaccine which may do just that.

In a joint collaborative effort involving Tulane National Primate Research Center (TNPRC), the National Institutes of Health and the U.S. Army, researchers have developed the first vaccine that provides complete protection against three types of equine encephalitic viruses in nonhuman primates.

There are no existing vaccines or treatments against Western, Eastern and Venezuelan equine encephalitis, all of which are spread by mosquitoes. During summer months when mosquitos increase, horse populations are particularly susceptible to fatal infection. Transmission from horses to humans can occur via mosquitoes and can cause serious illness and death in vulnerable populations like the elderly and children.

Using nonhuman primate and mouse models of aerosol infection, the study showed that the trivalent virus-like particle (VLP) vaccine induced an immune response and provided complete protection from all three viruses. The response was strong enough to effectively block the neurological effects of infection, which is normally present with any of the three viruses.

Chad Roy, PhD, director of Infectious Disease Aerobiology and Biodefense Research Programs at Tulane, said one reason this finding is significant is because of its possible influence on the field of bioweaponry. These encephalitic viruses are possible bioterrorism agents because of their potential to be aerosolized, underlining the need for a vaccine in the event of an attack.

“These findings are an important milestone in the development of a vaccine that could be employed in the event that these viruses are ever used in a deliberate release,” noted Roy.

Of course, the vaccine could also be used to prevent or slow the natural spread of equine encephalitic viruses.

“This is a significant step, not only in protecting human populations from possible threats of bioterrorism, but also protecting both animals and humans from natural vector-borne disease transmission,” said Vicki Traina-Dorge, PhD, associate professor of microbiology and immunology at Tulane.

As the global climate warms and human and animal populations increase, mosquito-borne infectious diseases have greater potential to spread. These vaccines could be highly useful in protecting global populations from both natural and man-made outbreaks.

For some, a summer internship is merely a stepping stone into their career. But for Brendan Creemer, a junior biology major at Portland’s Lewis & Clark College, a recent summer internship meant so much more.

Creemer has Usher syndrome, a genetic disorder that causes progressive vision loss and deafness. He spent much of the summer in the laboratory of the Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University (OHSU) with neuroscientists Martha Neuringer, PhD and Trevor McGill, PhD, working on a method to improve the ability to use stem cells as a possible treatment for the disorder.

For more than 40 years, Neuringer has taken on high school and college summer interns, but Creemer is the first intern to live with the often-debilitating symptoms of Usher syndrome.

“I’ve been working for many years on retinal diseases and potential therapies without that personal connection,” said Neuringer, a professor in the Division of Neuroscience at the ONPRC and research associate professor of ophthalmology in the OHSU School of Medicine. “It’s all the more motivation when you know what it’s like for someone facing this.”

Creemer sought out the internship after learning about the research through the OHSU Casey Eye Institute.

“You have that choice to either give up and assume everything is hopeless or choose to take action and not only help yourself but others around you as well,” he wrote of his experience.

Creemer’s summer project focused on a key issue for stem cell therapies: rejection of transplanted cells. When stem cells are delivered as therapies for any health issue, they are perceived as “non-self” by the recipient and attacked by the immune system. Creemer analyzed a possible method to suppress the immune system in rodents, which was then tested to see if it enhanced the survival of retinal stem cell transplants.

“It makes it so much more palpable and real when you see how someone deals with their limitation and overcomes it,” Neuringer said. “It was a perfect match.”

The scientists at the NPRCs across the country are focused on solving myriad genetic disorders. Discover more of our latest research here.

As scientists continue to make progress in the fight against human immunodeficiency virus (HIV), a recent discovery suggests that certain other microbes may play a role in how the body responds to vaccination.

According to researchers at the California National Primate Research Center (CNPRC) at the University of California, Davis (UC Davis), microbes living in the rectum could alter the effectiveness of experimental HIV vaccines.

Evidence from human and animal studies with other vaccines suggests supplements containing the bacteria Lactobacillus can boost antibody production, while treatment with antibiotics can hamper beneficial immune responses, according to Smita Iyer, assistant professor at the UC Davis Center for Immunology and Infectious Diseases and School of Veterinary Medicine. 

Iyer and her team specifically sought to learn if microbes living in the rectum and vagina—sites of HIV transmission—interacted with an experimental HIV vaccine similar to the HVTN 111 vaccine currently in early stage clinical trials in humans. According to Iyer, a vaccine that produces antibodies at the mucosal membranes where infection takes place is thought to be crucial.

The team studied rectal and vaginal microbes from rhesus macaques before and after they were vaccinated. While vaginal microbes did not show much difference before and after vaccination, rectal microbes did, with certain bacteria decreasing after vaccination. 

Furthermore, the amounts of the common gut bacteria Lactobacillus and Clostridia in the rectum correlated positively with the immune response. Animals with high levels of either Lactobacillus or Clostridia made more antibodies to certain HIV proteins, the researchers found. Prevotella bacteria showed the opposite pattern: High levels of Prevotella were correlated with weaker immune responses.

It’s not clear what the mechanism could be for some bacteria to boost local immune responses in a specific site in the body, Iyer said. However, targeting these bacteria could help scientists get the best possible performance out of vaccines that do not induce a particularly strong immune response, as is the case with HIV vaccines.

The NPRCs are actively conducting HIV/AIDS research across the country. Discover more ways our scientists are making progress against this disease in the ongoing pursuit of a cure.

Tuberculosis (TB) kills 1.6 million people every year and is one of the top 10 causes of death globally. And while it’s been kept under control in most places, more than 95 percent of cases and deaths are in developing countries, according to the World Health Organization (WHO).

Traditionally, it’s been difficult to prevent and treat TB in such regions, which is why Southwest National Primate Research Center (SNPRC) researcher Professor Jordi Torrelles, PhD, is focused on making a change. He developed a TB test that has been adapted for the challenging conditions typically encountered when diagnosing TB in developing countries.

“The way it’s done now, it takes 42 to 60 days before you get results from a TB test,” Torrelles said. “That’s before the patient is informed of results. When you factor that in, it’s more like 65 to 80 days from when the patient gives a sputum sample to when they learn whether they have TB.”

Torrelles traveled to Mozambique, Swaziland and South Africa in early 2019 to establish research collaborations for testing this cheaper, faster, easier way to diagnose TB. The current widely-used, commercially available TB test costs 608 USD. Torrelles’ improved version has a projected cost of just 9 USD.

What’s more, the current test does not indicate if a person is infected with drug-resistant strains of TB. Patients with these strains are even more difficult to treat, as they do not respond to the most commonly used TB drugs, requiring expensive, lengthy treatment. Torrelles and team started with what’s known as an “agar” test—which shows if the patient is infected with TB and whether the bacteria type or strain is resistant to three commonly used drugs for treatment—and developed a special color plate that can test for resistance to 11 drugs. They created two versions: one diagnostic, the other a treatment-tracking version to check if the patient is responding to the treatment.

In the past, results have usually been returned in 21 days for TB strains that can be treated with drugs, and up to 80 days for drug-resistant strains. If the SNPRC team’s new test plates are kept refrigerated, results can be seen as soon as three to 14 days, Torrelles said. And while many health care facilities in developing countries don’t have access to refrigeration, the improved diagnostic test doesn’t require it. Even if kept at room temperature, results can be interpreted between three and 19 days.

TB research is a top priority for scientists across the National Primate Research Centers (NPRC) network. Check out more ways we’re working to eliminate the disease for good.