In a groundbreaking leap towards a new Parkinson’s disease treatment, a stem cell therapy company has initiated a clinical trial involving human patients following the success of a novel therapeutic delivery method in non-human primates at the Wisconsin National Primate Research Center. This advance could revolutionize how we treat Parkinson’s disease. 

What is Parkinson’s? 

Parkinson’s disease is characterized as a condition that progressively impairs movement due to the loss of dopamine-producing neurons in the brain. Dopamine is a neurotransmitter crucial for coordinating movement. This leads to symptoms such as rigidity, slowness and tremors. While medications like L-DOPA can temporarily alleviate these symptoms, the drugs often lose effectiveness over time and can cause complications. 

A New Approach with Monkeys  

Researchers at the Wisconsin National Primate Research Center at the University of Wisconsin–Madison have successfully grafted dopaminergic neuronal progenitor cells into the brains of cynomolgus macaque monkeys. These cells, provided by Aspen Neuroscience, were grown from human induced pluripotent stem cells, or iPS cells. The process involved precise surgical techniques guided by intraoperative MRI, allowing for targeted delivery of the cells to areas of the brain most affected by the disease. 

The Human Connection 

The promising results in monkeys paved the way for human trials. The research highlighted the potential of using a patient’s own iPS cells to avoid immune rejection, a significant hurdle in cell therapy. This method not only aims to replace  

lost neurons but also to enhance the patients’ quality of life by reducing symptoms of depression and anxiety associated with Parkinson’s. 

Bridging the Gap to Human Trials 

The transition from animal models to human trials required meticulous planning and collaboration. The study tested different angles for cell delivery to minimize surgical risks and improve recovery times. The findings were crucial in obtaining approval from the FDA to start human trials, marking a significant step forward in the quest to find safe and effective treatments for Parkinson’s. 

Hope for the Future 

As the first human trials commence, this research not only represents a scientific breakthrough but also a sign of hope for improving the lives of millions suffering from Parkinson’s. The journey from lab to clinic underscores the power of innovative science and collaboration in tackling complex health challenges. 

In a groundbreaking stride toward combatting HIV, researchers have achieved a significant breakthrough in the quest for an effective treatment. Published in the prestigious journal Science on February 29, 2024, findings from a collaborative preclinical nonhuman primate study have illuminated a potential new avenue for managing HIV without the need for daily antiretroviral treatment (ART). 

Researchers at multiple institutions, including the Wisconsin National Primate Research Center and led by virologist James Whitney from Boston College and Harvard University, showcased the efficacy of a novel combination therapy involving an interleukin-15 superagonist therapy termed N-803 (marketed as Anktiva) along with broadly neutralizing antibodies (bNAbs). This promising therapy demonstrated the ability to enable the immune system to control HIV in individuals. 

Funded by the National Institutes of Health and the National Institute of Allergy and Infectious Diseases, the preclinical study conducted on rhesus macaques infected with chimeric simian-human immunodeficiency virus AD8 (SHIV-AD8) yielded encouraging results. The combination therapy of N-803 and bNAbs led to durable viral remission after discontinuation of antiretroviral therapy. 

Despite initial immune activation and transient viremia, the treatment showed only minor changes in the SHIV reservoir. Upon discontinuation of ART, approximately 70 percent of the treated macaques experienced long-term virus control for up to 10 months, marking a significant milestone in HIV research. 

These promising preclinical results have paved the way for the initiation of two Phase 1 clinical trials aimed at investigating the efficacy of N-803 and bNAbs in reducing viral loads in HIV-infected humans receiving antiretroviral treatment. One of the clinical trials, which includes an analytical treatment interruption to assess the impact of immunotherapies on post-therapy viral loads, is already underway at the Rockefeller University.  

Jon Levine, director of the Wisconsin National Primate Research Center (WNPRC), expressed optimism about the findings, highlighting the potential for widespread use of such therapies in HIV-infected patients. “This groundbreaking research not only offers hope for individuals living with HIV, but also represents a significant step forward in the global fight against the virus.” Levine said. 

As researchers continue to push the boundaries of medical science, the prospect of achieving sustained remission and ultimately finding a cure for HIV grows ever closer.  

When it comes to kidney transplants, compatibility between the donor and recipient is a critical factor for success. However, even when a donor and recipient are closely matched, long-term drug therapy is often necessary to suppress the recipient’s immune system and prevent the rejection of the transplanted organ. But what if there was a way to increase compatibility, reducing the need for lifelong anti-rejection medications? 

Researchers at the University of Wisconsin–Madison and Stanford University developed a groundbreaking approach that may revolutionize kidney transplants, allowing for greater compatibility between donors and recipients and potentially eliminating the need for immunosuppressant drugs. This method, tested in a nonhuman primate model, creates a dual immune system with the recipient and offers hope to kidney transplant patients, even when they are less closely matched to their donors. 

The Journey to Compatibility 

Led by Dixon Kaufman, a Professor of Surgery at UW–Madison and Director of the UW Health Transplant Center, the research team aimed to maintain kidney function without rejection in a monkey model that closely resembled human transplants. They also sought to prevent graft-versus-host disease, a complication when the donor’s immune cells attack the new host. 

According to the recent study published in Transplant International, the team worked with 11 monkeys from the Wisconsin National Primate Research Center. These monkeys had less tissue type matching than what had previously been attempted in human donor-recipient pairs. 

The major histocompatibility antigens, two key strings of tissue typing proteins found on the surface of cells, play a pivotal role in the immune system’s ability to recognize “self” and “non-self.” The monkeys in this tolerance induction study had just one match among these key protein strings, while successful human transplant pairings previously required two matches. 

The Innovative Procedure 

After receiving donor kidneys, the monkeys underwent a procedure involving thin beams of radiation, targeting key parts of their immune systems, temporarily suppressing them, and an infusion of blood and immune cells from their kidney donors. The goal was to create a mixed chimeric state in the recipients, where their immune system was a combination of two animals: part donor and part recipient.  

All animals in the study were gradually weaned off immunosuppressant drugs, and two monkeys maintained chimeric immune systems. These two animals remained healthy with normal kidney function for more than four years without experiencing rejection or graft-versus-host disease or needing drugs to suppress their immune systems. 

Dixon Kaufman noted, “This is the longest duration of tolerance induction reported in this kind of animal model. Although more challenging compared to identically matched pairs, this protocol shows it is feasible to achieve long-term tolerance between more distantly related pairs with tissue incompatibility.” 

A Brighter Future for Transplants 

Kaufman believes the knowledge gained through this research could have far-reaching implications for various donor transplants, including those from deceased donors who may be even more distantly related. As advancements continue, the hope for improved compatibility between donors and recipients becomes increasingly promising. 

A team of researchers recently delved into lower urinary tract (LUT) dysfunction, a common issue among older adults that brings challenges like incontinence, urinary infections, and reliance on catheters. These struggles often lead to a loss of independence and a need for extended care. But what causes this problem?

Researchers at the California and Wisconsin National Primate Research Centers alongside researchers from the Icahn School of Medicine at Mount Sinai set out to uncover the secrets behind LUT dysfunction, focusing on adult and aged female rhesus monkeys, giving them insights into how the issue develops in humans.

They discovered a connection between detrusor underactivity (DU), which affects bladder muscle tone, and specific metabolic markers. These markers act like clues that help researchers understand the bigger picture.

The bladder’s functioning relies on smooth muscle fibers arranged in a pattern known as the detrusor muscle. This unique structure allows the bladder to stretch and contract effectively.

Researchers also noticed patterns among the aged subjects. These subjects exhibited markers commonly associated with metabolic syndrome, such as changes in weight, triglyceride levels, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and high-sensitivity C-reactive protein (hsCRP). Interestingly, some markers, like Aspartate aminotransferase (AST), remained unchanged, while the AST/ALT ratio took an unexpected turn.

This means there is a link between detrusor underactivity and metabolic syndrome in older female primates. Factors like prior pregnancies and menopause didn’t sway the results, making this connection even more intriguing.

Dr. Ricki Colman, an associate professor of cell and regenerative biology at the University of Wisconsin–Madison and one of the study’s authors, emphasized the practical significance of their findings: “Our findings provide insights into possible mechanisms for age-associated detrusor underactivity and may guide new strategies to prevent and treat LUT dysfunction in older adults.”

As this chapter in the research unfolds, it’s clear that the relationship between LUT dysfunction and metabolism holds promise for shedding light on a common issue and uncovering new ways to address it.

National Primate Research Centers Prioritize Openness for Scientific Progress

At the forefront of biomedical and behavioral research are the seven National Primate Research Centers (NPRCs). They form a vital network dedicated to conducting and enabling groundbreaking research to improve human and animal health. Studies at the centers include development & aging, genetics & genomics, infectious disease, neuroscience & brain disorders, and reproduction & endocrinology. The NPRCs have been instrumental in driving discoveries crucial for overcoming health challenges and in helping the public understand the significance of research that involves animals.   

A Comprehensive Approach  

A priority of the NPRCs is to share information via local, regional and national outreach. Through a multifaceted approach, the NPRCs foster education and dialogue, ensuring openness about their research and the expert care of animals involved in NPRC research studies.   

From participating in local events to leveraging digital platforms, the NPRCs employ diverse strategies to make connections. NPRC.org provides the latest information for the public, and NPRCresearch.org, which is undergoing updates, ensures the scientific community has comprehensive information about the resources the NPRCs offer NIH-funded researchers. Through timely and engaging content, the NPRCs strive to explain the highly regulated research process and showcase their contributions to scientific progress.   

A Legacy of Excellence  

With a history spanning more than six decades, the NPRCs stand as pillars of scientific expertise and exemplars of public outreach. The U.S. Animal Research Openness initiative (USARO) recently featured information about the NPRCs’ outreach programs on the USARO website. This article provides encouragement for other research centers to follow the NPRC lead.   

A Future Filled with Accurate Information  

As the NPRCs continue to make scientific discoveries, their dedication to openness will continue to expand. The NPRCs believe openness helps empower individuals to make informed decisions, is critical to instilling confidence in scientific research and care of research animals, inspires future generations of scientists and ensures the public has accurate information about how research with animals is improving lives.  

Every day, the seven National Primate Research Centers (NPRCs) conduct and enable collaborative research studies to improve human and animal health. For more than five years now, we’ve been sharing our latest news and scientific advancements with you via NPRC.org and @NPRCnews (X), and there’s more coming your way. 

To ensure the NPRCs provide the topics of most interest to our readers and followers, we looked back at your favorite stories to help us move forward. Your top interests span behavior and psychology, infectious disease and neuroscience and brain disorders research. We will continue to share news that represents what you have most enjoyed, and we will also bring you information that reflects the breadth and depth of research across the NPRC network.   

We appreciate our readers and followers, and encourage you to take another look at your favorite blogs about NPRC research, to share the information with your family, friends and colleagues, and to continue connecting with us via NPRC.org, @NPRCnews and, now, on the new NPRC LinkedIn account. Via these resources, you’ll always be able to access the latest news on NPRC research that is helping people across generations and around the world live longer, healthier lives.   

Behavior and Psychology 

1. The Effects of Wildfire Smoke Exposure in Early Pregnancy 

A study by California NPRC and UC Davis researchers investigated the effects of wildfire smoke exposure on infant monkeys during early pregnancy. The study found that exposure led to increased inflammation, reduced stress response, memory deficits and a more passive temperament in the monkeys. The findings suggest environmental changes during pregnancy can have lasting effects on offspring.  

Infectious Disease 

2. A Deadly Relationship: Stopping the Progression of Tuberculosis in HIV Patients   

Researchers at the Southwest National Primate Research Center have discovered chronic immune activation in the lungs plays a crucial role in the progression of tuberculosis (TB) and HIV co-infection. This dysfunction hampers the body’s ability to fight off infections. The study suggests the need to develop treatments targeting chronic immune activation alongside antiretroviral therapy (ART). TB and HIV are global pandemics that reinforce each other, affecting a significant portion of the world’s population. The findings offer hope for improved treatment strategies in the next decade. 

3. New Possible Correlation Between Lyme Disease and Lewy Body Dementia  

At Tulane National Primate Research Center, researchers discovered intact spirochetes of Borrelia burgdorferi, the bacterium that causes Lyme disease, in the central nervous system of a 69-year-old woman who received multiple rounds of antibiotic treatment. The presence of this bacterium coupled with her persistent neurological decline raises the possibility of a correlation between Lyme disease and Lewy body dementia. This finding highlights the bacterium’s persistence despite targeted therapy and emphasizes the need for further research to comprehend its role in severe neurological conditions. 

4. Are DNA Vaccinations a Perennial Answer to the Flu?  

Researchers at the Washington National Primate Research Center are developing a universal flu vaccine that could protect against all strains of the influenza virus. Using a DNA vaccine administered through the skin, the team has achieved promising results in macaques, providing 100% protection against a previous flu virus. This approach could eliminate the need for annual flu shots and be quickly deployed during pandemics. The researchers believe this technology could also be effective against other viruses and outbreaks. 

Neuroscience & Brain Disorders 

5. Past Social Experiences May Affect Brain’s Response to Oxytocin

A study at the Emory (formerly Yerkes) National Primate Research Center and Emory University showed the response of neurons to oxytocin, a chemical involved in social bonding, can vary based on an individual’s past experiences. Using female prairie voles, the researchers examined the nucleus accumbens, a brain region related to pair bonding. They found that oxytocin reduced neuron firing before bonding and increased it afterward, when triggered. The study also revealed a connection between oxytocin signals and endocannabinoids, affecting defensive interactions. These findings provide insights into how prior experiences influence oxytocin’s impact on brain circuits. 

6. NPRC Study May Have Found Link That Causes Anxiety and Depression  

Researchers at the Wisconsin National Primate Research Center and the University of Wisconsin-Madison have discovered brain pathways in juvenile monkeys that could contribute to anxiety and depression later in life. By studying the connections between specific brain regions, they found a correlation between synchronization and anxious temperament. These findings may lead to better treatment approaches and help identify gene alterations associated with anxiety. 

7. The Drinking Gene: Could Alcoholism Be Inherited?  

Research conducted at Oregon National Primate Research Center has identified a gene, GPR39, as a potential target for developing medication to prevent and treat alcoholism. By modifying protein levels encoded by this gene in mice, the researchers observed a significant reduction in alcohol consumption. They also found a link between alcohol and the activity of this gene. The study draws attention to the importance of cross-species approaches to identify drugs for treating alcohol use disorder. Further investigations are under way to determine if the same mechanism applies to humans. These findings offer potential insights for developing drugs to address chronic alcoholism and mood disorders. 

Marina Emborg, medical physics professor and director of the University of Wisconsin–Madison’s Preclinical Parkinson’s Research Program, focuses on understanding and developing treatments for neurological disorders in a highly collaborative, interdisciplinary fashion. 

In her article, “Reframing the perception of outliers and negative data in translational research,” published last month in Brain Research Bulletin, Emborg describes how publishing negative or unexpected data from a research project helps scientific research advance. 

Scientific results are termed ‘positive’ when supporting the driving hypothesis and ‘negative’ when countering it. Both can be equally informative. But it is noteworthy that ‘negative’ data differs from ‘useless’ data. 

• Useless data is defined as the results obtained by a biased or poorly performed experiment. 
• Negative data are unexpected results that prove or disprove a hypothesis in a way not previously known. 

“Overall, the paper aims to reframe the perception of working with, reporting and reviewing unexpected data as an opportunity to provide rationale for innovative ideas, prevent the misuse of limited resources and, ultimately, strengthen the reputation of a scientist,” writes Emborg in the paper’s abstract. 

While scientists may be initially disappointed by negative data, analyzing it is helpful for the scientific community, including individual scientists, explains Emborg, whose lab is based at the Wisconsin National Primate Research Center. 

Through a new study with marmosets, scientists are learning more about how neuroestrogens may be integral to supporting libido and maintaining female sexual health. 

“The lack of effective treatment options for women with Female Sexual Interest Arousal Disorder (FSIAD) and obesity is likely related to the lack of understanding regarding the biology of female sexuality, as well as the regulation of body weight and metabolism,” reports first author Marissa Kraynak, Ph.D. Kraynak was a research fellow in the Endocrinology and Reproductive Physiology Program at the University of Wisconsin–Madison when the study was underway, training under David Abbott, Ph.D., and Jon Levine, Ph.D., at the Wisconsin National Primate Research Center. She is now the Director of Health Policy Research at Insure the Uninsured Project in Sacramento. 

Doctors often give women synthetic estradiol to compensate when women need ovariectomies due to cysts, cancer, or other problems. But ovarian estradiol, found in the skin, adipose tissue, brain, and ovaries, can cause harmful side effects, including cardiovascular disease and cancer. 

Kraynak reported bioactive estradiol derived from the brain, as opposed to the ovaries, plays a pivotal role in maintaining sexual receptivity in female nonhuman primates. During the study at the University of Wisconsin–Madison center, the ovarian estradiol-depleted female monkeys remained receptive toward at least 35 percent of male mounting behaviors.  

Only by removing both ovarian and extra-ovarian estradiol, including hypothalamic sources, were female marmosets consistently sexually unreceptive to male sexual advances. This study provides hope for better treatment options for women with Female Sexual Interest Arousal Disorder (FSIAD) and obesity. 

Ceramides are fats or lipids found in skin cells and make up approximately 35% of your outer skin layer. They are widely known for retaining skin moisture and preventing germs from entering the body. But now they could also be used as early clinical detectors of the onset of metabolic syndrome – a cluster of conditions that increase the risk of heart disease, stroke, and type 2 diabetes.

Researchers at the Wisconsin National Primate Research Center used rhesus monkeys during a two-year ceramides study. Rhesus monkeys are similar in metabolic function to humans and, like people, can get obesity, diabetes, heart disease, high blood sugar and high blood pressure. The researchers fed 16 genetically diverse, healthy yet overweight adult monkeys the same diet and kept them in a controlled environment. Half developed metabolic syndrome and showed significant composition differences of circulating ceramides when compared to monkeys who did not develop the syndrome.

“Seeing these differences earlier on, when animals were clinically indistinguishable from one another, provides new insight on metabolic impairment and how we might distinguish among individuals to identify those at elevated risk for disease,” Anderson said.

As metabolic syndrome becomes increasingly more common among humans, currently affecting about a third of U.S. adults, the necessity of early preventive strategies is critical.

While current HIV treatment reduces viral load, or the amount of HIV in the blood, there is no cure for the disease. Antiretroviral therapy (ART) involves either taking a shot or a daily pill. Then a test can’t often detect HIV because the viral load becomes so low. Unfortunately, skipping a treatment, even now and then, gives the remaining virus a chance to multiply rapidly, weaken the immune system and cause illness. 

A truly effective treatment for chronic HIV infection would eliminate these residual infected cells, known as the HIV reservoir. A drug called N-803, developed by ImmunityBio, Inc., has the potential to be such a therapeutic. N-803 is now in clinical trials for treating non-muscle invasive bladder cancer that does not respond to standard therapy. The drug received Fast Track and Breakthrough Therapy designations in 2017 and 2019, respectively, from the U.S. Food and Drug Administration (FDA) for this cancer based on its demonstrated activity as a compound that stimulates the immune system. 

Shelby O’Connor, a professor of pathology and laboratory medicine at the University of Wisconsin–Madison and a scientist at the Wisconsin National Primate Research Center, recognized that N-803 might also have the potential to treat HIV. She and her research team evaluated this drug’s effectiveness in the context of various immune states and concurrent therapies in simian immunodeficiency virus (SIV) models, using both rhesus and cynomolgus monkeys. 

The researchers discovered overall that primates with low viral copies before N-803 treatment improved their ability to kill SIV during treatment. Primates with higher viral load before treatment showed chronic activation of T-cells, resulting in immune “exhaustion” and leaving these immune cells that target SIV unable to fight viral infection even with the treatment. 

This NIH-funded research suggests the drug is most effective in hosts with a natural pre-existing immunological ability to control SIV replication. This aligns with N-803’s known ability to increase the proliferation of both natural killer cells and T cells in hosts with higher-functioning immune systems. 

The O’Connor lab plans to continue investigating how N-803 may react differently in individuals that control HIV and SIV compared to settings where the virus is not controlled.