June 7, 2022

Human immunodeficiency virus (HIV) attacks the body’s immune system, resulting in rashes, fevers, fatigue, swollen lymph nodes, and other symptoms. It affects over 37 million people globally. When left untreated, HIV infections can progress to acquired immunodeficiency syndrome (AIDS), leading to a damaged immune system, severe opportunistic infections, and death.

 

Most replicating HIV – and its monkey version, simian immunodeficiency virus (SIV) – is found in follicles of the lymphoid tissues. However, most cytotoxic T-lymphocytes, the cells clearing HIV from the body, cannot reach the follicles. This explains the need for lifelong use of antiretroviral therapy’s current standard treatment. However, only 57% of those living with HIV are undergoing antiretroviral therapy, which leaves the rest able to infect others with the virus. Therefore, there is an urgent need for new treatment options, especially for those who do not have lifelong access to healthcare.

 

A group of AIDS researchers working with immunology and animal care experts on rhesus monkeys at the Wisconsin National Primate Center investigated the possibility of a new therapy targeting virus-specific T-cells to the follicles. They did so by engineering therapeutic T-cells to enter and concentrate in the lymphoid follicles to reduce viral replication. Led by Pamela Skinner, professor of veterinary and biomedical sciences at the University of Minnesota, the team used T-cells to express a chimeric antigen receptor (CAR) targeting the SIV virus. They added a follicular homing receptor called CXCR5 so the CAR/CXCR5 T-lymphocytes could kill the infected cells in the lymphoid follicles. The homing receptor allowed the T-cells to migrate into the follicles, which previously limited the effectiveness of the body’s response to infection.

 

In six SIV-infected rhesus monkeys, the CAR/CXCR5 T-cells were able to migrate to the follicles within two days and directly interact with the virally infected cells. Fluorescent imaging allowed the researchers to discover these T-cells could replicate and increase within the follicles. Even though levels of the specialized T-cells declined within four weeks after administration, the treated primates were able to maintain lower concentrations of SIV in their blood and follicles than those not given the CAR/CXCR5 T-cell immunotherapy. The researchers and veterinarians also looked at possible side effects of this treatment and found none of the primates had a poor reaction to T-cell administration.

 

The study, published in Public Library of Science Pathogens, provided preliminary evidence for effective and safe treatment of engineered T-cells for HIV infection. Data from these researchers set the stage for future preclinical studies involving larger populations of non-human primates to confirm the effectiveness of this treatment, along with studies looking at combining this treatment with other therapies.

January 28, 2022

Alzheimer’s disease (AD) is a progressive, neurodegenerative disease that destroys memory and other important mental functions. AD affects more than 44 million people worldwide and more than six million Americans. Given this prevalence, studying AD is a high priority, and researchers have been searching for better ways to learn more about the disease.

Now, researchers at the Wisconsin National Primate Research Center and other institutions at UW-Madison have shown rhesus monkeys can be a new, translational model for studying late-onset Alzheimer’s disease. “Age is a major risk factor for late-onset Alzheimer’s disease (AD) but seldom features in laboratory models of the disease,” the researchers write in the scientific publication Aging Cell.

The researchers studied brain tissues from transgenic mice, old monkeys with age-related amyloid plaques and post-mortem brain tissue from donors who were aged 72 to 96 and diagnosed with AD after death. This approach provides an alternative to the most common approaches to modeling AD, which tend to use young mice in which plaques and tangles are genetically imposed and seldom include age as part of the study design.

The new study design, however, shows the aged environment impacts inflammatory processes linked to neurodegeneration. In the monkeys and humans, where plaques develop as a function of age, each demonstrated differences from mice in the immediate vicinity of amyloid plaques, but were similar to each other.

In all three species, the authors discovered new structures enriched in mitochondria surround the plaques, and the presence of these plaques influences metabolism. In the monkeys and humans, said Dr. Ricki Colman of the WNPRC, “this mitochondrial dysfunction appears to be suggestive of Alzheimer’s disease.”

The published study concludes that, given the clear parallels between amyloid plaques in monkeys and humans, further studies in nonhuman primate models are warranted. Monkey models are more likely to translate to human disease than mouse studies and could help advance treatments for AD.

 

November 18, 2021

Endometriosis is a condition that occurs when patches of the endometrium, a layer of tissue lining the uterus, travel throughout the body and attach to other organs, like the ovaries or intestines. Unfortunately, 1 in 10 women experiences pain and even infertility due to this disorder. Current treatments include surgery to remove the mislocated tissue and drug treatment to suppress ovarian activity, which can lead to weight gain, mood changes and headaches. 

After decades of study, a team of researchers, including Wisconsin National Primate Research Center scientists, discovered a possible new therapy for endometriosis that zeroes in on a particular region of chromosome 7 as the responsible gene. 

A thorough study of the DNA of women in 32 families with deep-rooted histories of endometriosis helped researchers narrow in on this single gene variant – neuropeptide S receptor 1 (NPSR1) – which they found in many, but not all, of the women with more severe cases of endometriosis.  

To learn more about this complex disease, researchers simulated endometriosis in mice by injecting bits of bacteria or uterine lining into their abdomens while attempting to silence the culprit gene. The researchers saw positive results with the rodents experiencing less inflammation and abdominal pain.  

As a next step, researchers will study this same treatment in monkeys, which have been an animal model for endometriosis studies for several decades. Joseph Kemnitz, former director of the Wisconsin National Primate Research Center, explains, “We documented the similarities of endometriosis in our monkeys compared to affected women in collaboration with Stephen Kennedy at Oxford.” The teams recognized the Wisconsin monkeys offered an excellent opportunity to examine endometriosis and have continued building on early results that revealed a familial pattern, suggesting a genetic risk.

As genomic tools continue to advance and analysis costs decrease, the rate of testing treatments stands to increase. Such comprehensive scientific progress is excellent news for the pursuit of improved human health. 

Source: Science Translational Medicine on Aug. 25, 2021. 

October 20, 2021

Dengue spreads to humans through the bite of an infected mosquito generally living in tropical climates. Symptoms (lasting 2-7 days) commonly seen with dengue include fever, nausea, rash, aches, and pains.

While most people who contract the virus see minimal long-term effects, the Wisconsin National Primate Research Center is studying whether the severity of maternal and fetal Zika virus infection increases in pregnant women who previously had dengue fever.

This first-ever study relating dengue to Zika arose from a concern that a previous dengue infection may become the catalyst leading to more potentially dangerous immune system responses when contracting Zika, especially in pregnant women and their fetuses.

Rhesus macaques were used for the study because their placental development closely mimics humans. Using them as the control, researchers uncovered prior exposure has no measurable impact on Zika replication in maternal plasma. All animal pregnancies resulted in healthy births and infants (in contrast to a small percentage of human infants born to women infected with the disease).

Researchers believe further study to understand the risks of antibody-dependent enhancement to pregnant women worldwide is needed as vaccines against dengue and Zika are developed.

Want to know more about the ongoing fight to eliminate Zika? Here are some additional ways NPRC scientists across the country are making progress against this disease.

Sources: https://www.cdc.gov/dengue/index.html

 

Note: The NPRCs will update this blog with our latest COVID-19 news.

Since beginning COVID-19 research in early 2020, NPRC researchers have made encouraging progress in efforts to better understand, diagnose, prevent and treat this novel disease. We’re committed to conducting and enabling research to end this global pandemic and to providing information so the public has ready access to our scientific results.

Our most recent COVID-19 news includes: 

Below is even more information about our extensive and collaborative COVID-19 research:

Diagnostics:

Prevention:

Treatments:

Additional NPRC COVID-19 News:

Bookmark this page so you can easily return here for the latest NPRC COVID-19 research information. We’ve also compiled a list of resources here and provided links to previous NPRC COVID-19 news and national media stories here.

June 22, 2021

About 30 percent of people who have severe anxiety and depression do not find sufficient relief in available medications and psychotherapy, causing them chronic, debilitating symptoms and a significant risk of suicide. To help end this debilitation, University of Wisconsin–Madison researcher Ned Kalin, MD, and his team are studying how to dial down overactive responses to potential threats.

The researchers are using an established method, called DREADDs (Designer Receptors Exclusively Activated by Designer Drugs), in monkeys at the Wisconsin National Primate Research Center (WiNPRC) to make small changes to genes in targeted cells to alter cell behavior. The idea is to coax neurons to produce a unique version of a protein, called a receptor. These “designer receptors” can receive chemical signals that regulate the cells’ function and affect how they communicate with other cells. Unlike other receptors in the brain that respond to naturally occurring chemical signals, the DREADDs only respond to a chemical not naturally present — a “designer” drug matched to the designer receptor.

“When such a drug interacts with DREADDs, you have the possibility of ‘fine-tuning’ the function of the brain cell that is now expressing this receptor,” says Patrick Roseboom, PhD, senior scientist and a lead study author.

The researchers injected a low dose of a psychiatric medication, Clozapine, in five monkeys to activate DREADDs in cells in the amygdala, the brain region responsible for regulating emotions. The researchers then tested the monkeys in a mildly stressful situation, placing them near an unfamiliar human, which is similar to how healthcare professionals assess anxiety levels in children. The researchers’ observations of the monkeys’ behavior and levels of stress hormones showed the most anxious monkeys freeze — becoming quiet and very still.

When the researchers gave the Clozapine before the stressful situation, the monkeys with the DREADDs experienced a significant reduction in freezing, while a control group without the DREADDS showed no change in behavior. 

The success of this proof-of-concept study is providing hope for using gene therapy and methods, such as DREADDs, to treat the millions of people who live with severe and treatment-resistant psychiatric illnesses. Read more about the NPRCs’ anxiety and depression research here.

 

May 25, 2021

Each year in the U.S., millions of people receive general anesthesia, and a small proportion of those patients actually regain some awareness during their medical procedures.

A recently published study about brain activity representing consciousness could help prevent that potential trauma as well as help scientists define which parts of the brain are key to the conscious mind. Such information could lead to more accurate measurements of patients undergoing anesthesia, improve treatment outcomes for people who have consciousness disorders and help people in comas maintain a continuous level of consciousness.

Yuri Saalmann, a University of Wisconsin-Madison psychology and neuroscience professor, and his research team recorded electrical activity in about 1,000 neurons surrounding each of 100 sites throughout the brains of a pair of monkeys at the Wisconsin National Primate Research Center (WiNPRC). The researchers recorded activity during several states of consciousness: under drug-induced anesthesia, light sleep, resting wakefulness and roused from anesthesia into a waking state through electrical stimulation of a spot deep in the brain.

To sift out characteristics that best indicate whether the monkeys were conscious or unconscious, the researchers used machine learning. They input their large pool of data into a computer, told the computer which state of consciousness had produced each pattern of brain activity and asked the computer which areas of the brain and patterns of electrical activity corresponded most strongly with consciousness.

Surprisingly, the results pointed away from the frontal cortex, which is the part of the brain healthcare professionals typically monitor to maintain patient safety while under general anesthesia and the part most likely to exhibit slow waves of activity long considered typical of unconsciousness.

“In the clinic now, they may put electrodes on the patient’s forehead,” says Mohsen Afrasiabi, an assistant scientist in Saalmann’s lab. “We propose that the back of the head is a more important place for those electrodes because we’ve learned the back of the brain and the deep brain areas are more predictive of state of consciousness than the front.”

And while both low- and high-frequency activity can be present in unconscious states, complexity best indicates a waking mind. “You need more complexity to convey more information, which is why it’s related to consciousness,” says graduate student Michelle Redinbaugh. “If you have less complexity across these important brain areas, they can’t convey very much information. You’re looking at an unconscious brain.”

Read more about our consciousness research and how monkeys are helping improve patient care here.

May 11, 2021

Promising results from the Wisconsin National Primate Research Center (WiNPRC) are giving hope to the millions of people who live with Parkinson’s disease (PD). By grafting neurons from monkeys, WiNPRC researchers relieved the debilitating movement and depression symptoms associated with the disease.

The researchers used induced pluripotent stem cells from the monkeys’ own bodies to make dopaminergic neurons. which produce dopamine, a chemical that transmits signals between nerve cells. PD damages these neurons and disrupts the signals, making it progressively harder for people who have PD to coordinate their muscles for even simple movements and causing rigidity, slowness and tremors, which are the disease’s hallmark symptoms. Patients — especially those in earlier stages of Parkinson’s — are typically treated with drugs, such as L-DOPA, to increase dopamine production.

“Those drugs work well for many patients, but the effect doesn’t last,” says Marina Emborg, a Parkinson’s researcher at WiNPRC. “Eventually, as the disease progresses and their motor symptoms get worse, they are back to not having enough dopamine, and side effects of the drugs appear.”

To develop additional treatment options, the researchers used real-time magnetic resonance imaging (MRI)  to inject millions of dopamine-producing neurons and supporting cells into each monkey’s striatum, an area of the brain that is depleted of dopamine as a consequence of the ravaging effects of Parkinson’s.

Half the monkeys received cells from other monkeys (an allogenic transplant), and the other half received grafts made from their own induced pluripotent stem cells (called an autologous transplant). The allogeneic monkeys’ symptoms remained unchanged or worsened, but the autologous monkeys began making significant improvements within six months and even more within a year — dopamine levels doubled for some and tripled for others.

Emborg says examples of the improvements included the autologous animals moving more and grabbing food much faster and easier. She adds, “Although Parkinson’s is typically classified as a movement disorder, anxiety and depression are typical, too. Symptoms that resemble depression and anxiety — pacing, disinterest in others and even in favorite treats — abated after the autologous grafts grew in.”

These promising results add to the growing body of NPRC research into improving lives for people who live with PD. Read more about our PD research here.

April 27, 2021

Did you know the rhesus macaque is the most widely studied nonhuman primate in biomedical research? The U.S. research colonies of rhesus macaques were founded primarily with animals imported from India decades ago and with the addition of Chinese-origin rhesus macaques over time. A deep understanding of their evolution and genetics is key to recognizing the origins of human traits and identifying disease genes of value to improving human health.

Rhesus macaques at the seven National Primate Research Centers (NPRCs) are key in the discovery and development of new and robust models of human disease and in evaluating the effect of genetic variation on experimental treatments prior to human clinical trials.  

In a recent publication in Science that detailed researchers’ use of advanced sequencing technology and analysis of more than 850 macaques across the seven NPRCs, researchers present a complete reference genome for the rhesus macaque. “In particular, we can now finally tackle some of the more complex regions of the genome and begin to understand how new genes evolve including the processes that have shaped them,” says University of Washington genome sciences professor and senior author in the paper, Evan Eichler, PhD.

In addition, the study identified animals that naturally carry potentially damaging genetic mutations, allowing researchers to better understand genetic variation and susceptibility to diseases of relevance to humans. So far, the findings reveal thousands of naturally occurring genetic variants (mutations), including those in genes linked to Autism Spectrum Disorder and other neurodevelopmental disorders in humans, such as SHANK3.

Jeffrey Rogers, PhD, associate professor at the Human Genome Sequencing Center and Department of Molecular and Human Genetics at Baylor College of Medicine and co-author of the paper explains, “Rhesus macaques are important for studies of conditions ranging from infectious disease (including COVID-19) to neuroscience, cancer and reproductive biology. A high-quality reference genome can aid researchers who are looking to understand the causes of various illnesses or aiming to develop treatments.”

The study is a great example of a broad collaboration across the NPRCs and other research centers in the U.S. that will continue to make a difference in human health. By identifying rhesus macaques that carry naturally occurring mutations, NPRC and other researchers are now able to examine biobehavioral traits associated with mutations. The researchers can also follow the monkeys’ offspring, and, in some cases, actually create new breeding groups to generate animals with specific genetic mutations and phenotypes. 

“This new information will lay the foundation for us to create naturally occurring models of human genetic diseases,” says Paul Johnson, MD, director of the Yerkes (now Emory) NPRC. “The development of these new models could have a profound impact on our ability to translate research in animal models into treatments and cures in people,” he continues.

To learn more about NPRC advances in genetics and genomics, explore additional research here. 

April 13, 2021

As the coronavirus (COVID-19) pandemic continues, scientists at the Wisconsin National Primate Research Center (WiNPRC) have kept their focus on the tiniest shifts in the virus’ genetic material.

Beginning with the first known case of the virus in Wisconsin in February 2020, researchers in the WiNPRC’s Global Infectious Disease Division have been sequencing the genomes of as many virus samples as they can process, reading each letter of genetic code.

It’s critical to expand virus genome sequencing across the U.S. as COVID-19 shifts and evolves, sometimes into more contagious variants. The more people the virus infects, the more likely genetic mutations will happen.

“The current estimate is that it makes one of those mistakes — a mutation — for about every two new people infected,” says Thomas Friedrich, WiNPRC scientist and University of Wisconsin–Madison School of Veterinary Medicine professor. As different viruses take various paths to infect more people over time, he adds, they accumulate different combinations of mutations. Researchers can use those combinations like fingerprints to track how different lineages of the virus spread through space and time.

Drawing samples from patients in Dane County and nearby Milwaukee County, Friedrich and WiNPRC colleague David O’Connor, UW–Madison School of Medicine and Public Health professor, have sequenced viruses from more than 3,200 infections. Their most pressing concern is keeping watch for virus variants believed to be more adept at infecting people or possibly carrying mutations that make vaccines and common treatments less effective. They post surveillance results online as soon as sequences are complete.

Nationally, fewer than 0.5 percent of all viruses have been sequenced. In Dane County, the researchers have sequenced 5 percent of all cases, a figure that represents their decades of experience and their work at WiNPRC to stay ahead of global HIV, influenza and Zika virus pandemics.

A coordinated sequencing system in the U.S. could help end this pandemic and the next. “You will see a benefit for HIV, for influenza, for whatever comes along,” O’Connor says. “You want to be able to track which viruses are circulating because it will save lives.”

Note: The UW–Madison researchers received funding from the Centers for Disease Control and Prevention’s SPHERES program (Sequencing for Public Health Emergency Response, Epidemiology, and Surveillance), Fast Grants (a group of nonprofits and private donors) and the Wisconsin Partnership Program. 

Back to top