Lyme disease, transmitted through tick bites, can leave patients with persistent neurological symptoms even after antibiotic treatment. However, a recent study conducted by Tulane University researchers offers hope to those suffering from long-term effects of the bacterial infection. 

Key Findings 

The study, published in Frontiers in Immunology, identifies fibroblast growth factor receptor (FGFR) inhibitors as a promising new approach to treating lingering neurological symptoms associated with post-treatment Lyme disease syndrome. These inhibitors  reduced inflammation and cell death in brain and nerve tissue samples infected with Borrelia burgdorferi, the bacterium responsible for Lyme disease. 

Research Approach 

Principal investigator Geetha Parthasarathy, PhD, led the study, treating nerve tissue with live or inactivated Borrelia burgdorferi followed by FGFR inhibitors. Results demonstrated a notable reduction in inflammatory markers and cell death, suggesting the potential efficacy of targeting FGFR pathways in addressing persistent neuroinflammation. 

Implications and Future Directions 

While further research is needed to translate these findings into clinical treatments, the study represents a significant advancement in understanding and potentially managing post-treatment Lyme disease syndrome. By focusing on underlying inflammation, researchers aim to develop treatments that improve the quality of life for patients affected by this debilitating condition. 

Supported by funding from the Bay Area Lyme Foundation and resources from the Tulane National Primate Research Center, this study opens new avenues for research and treatment development, offering renewed hope to Lyme disease patients grappling with lasting symptoms. 

In the battle against opioid addiction, a groundbreaking development has emerged: a novel vaccine designed to combat oxycodone addiction. This innovative vaccine has shown promise by generating antibodies in the bloodstream, effectively preventing the drug from reaching the brain and exerting its addictive effects. 

Funded by the California National Primate Research Center’s Pilot Research Program at the University of California, Davis, the study behind this vaccine sheds light on a potential therapeutic option for the millions affected by opioid use disorder (OUD) in the United States. 

Led by Kathryn Frietze, an assistant professor at the University of New Mexico School of Medicine, along with graduate student Isabella Romano, the research evaluated the vaccine’s protective abilities in animal models. Notably, the study also explored the vaccine’s interactions with other OUD treatments, such as Methadone and Buprenorphine. 

The mechanism of action behind this vaccine is intriguing. By stimulating the production of antibodies that recognize and bind to oxycodone, the vaccine hinders the drug’s ability to cross the blood-brain barrier and bind to specific receptors in the brain. This impediment prevents the drug from exerting its addictive effects, offering a novel approach to addiction treatment. 

Results from the study demonstrated the vaccine’s efficacy in elevating antibody levels in both mice and nonhuman primates. Importantly, the vaccine showed no adverse health effects and effectively prevented oxycodone from reaching the brain when challenged with the drug. 

Beyond its efficacy, the vaccine also offers practical advantages for clinical use. It remains effective following temperature fluctuations, making it suitable for real-world clinic settings. Moreover, it exhibits minimal cross-reactivity with other OUD treatments, ensuring compatibility with existing treatment plans. 

Looking ahead, Frietze and her team will continue to investigate the vaccine’s protective capacity, focusing on its effects on respiratory depression and pain perception. They will also explore whether vaccinated animals remain responsive to other OUD treatments. 

As Romano emphasizes, addressing concerns and acceptability issues from both patients and providers is crucial in the development of opioid vaccines. By addressing these obstacles, researchers aim to position vaccines as a viable and accessible treatment option for opioid addiction, offering hope for a brighter future in the fight against this devastating epidemic.

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. 

In medical research, discoveries come from persistence, creativity, and new angles.  

At the forefront of the endeavor to develop an HIV vaccine is Marie-Claire Gaudin, PhD, a professor at Texas Biomedical Research Institute and the Southwest National Primate Research Center. She has dedicated over a decade to crafting an innovative vaccine strategy that aims to halt virus as it enters the body. With support from NIH, including a recently awarded $3.8 million grant, Dr. Gauduin’s visionary approach is paving the way for a new era in HIV prevention. 

The Quest for an Effective HIV Vaccine 

The challenge posed by HIV is two-fold: its rapid spread through the body within days of infection and its ability to reach peak viral levels within two weeks. Traditional vaccine development has struggled to keep pace with the virus’s swift assault on the immune system. Enter Dr. Gauduin’s idea: why not intercept HIV at the very point of entry before it infiltrates cells and establishes its stronghold? 

Dr. Gauduin reflects on her “aha” moment, saying, “I had this idea as a postdoc. I thought it had to be naïve because nobody was talking about it. It was obvious and simple; I thought someone would have already done it.” Little did she know that her seemingly straightforward insight would set the stage for a paradigm shift in vaccine design. 

Unveiling the Strategy 

Dr. Gauduin’s novel approach is laser-focused on the mucosal epithelium—the inner lining of the vagina and rectum, where HIV is most likely to breach the body’s defenses. The vaccine sparks the production of antibodies specifically within these regions, strategically positioning them to thwart the virus’s advance.  

Additionally, it is engineered to engage the basal cells—the foundational building blocks of the lining. These basal cells are pivotal in renewing the epithelial layer, ensuring the body’s natural defense mechanisms remain fortified. The vaccine, nestled within the basal cells, is then passed on to new cells as the old ones die off, establishing an ongoing barrier against HIV entry. 

A Masterstroke in Prevention 

The vaccine’s potency is further enhanced by its composition as a live attenuated vaccine. Unlike its predecessors, it’s constructed from HIV’s genetic code, meticulously modified to remove harmful components. While live attenuated vaccines have been successful for diseases like smallpox and yellow fever, HIV’s propensity to mutate has thwarted previous attempts. 

From Lab Triumphs to Real-world Impact 

Dr. Gauduin’s vaccine exhibited impressive results in early trials involving nonhuman primates, and her sights are now set on expanding these promising outcomes. The following research phase entails a larger group of animals; a necessary step to establish safety and efficacy benchmarks before embarking on human clinical trials. As the vaccine progresses, Dr. Gauduin is also investigating alternative delivery methods to optimize efficiency, a crucial consideration for eventual mass immunization efforts.  

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. 

The battle against COVID-19 has been relentless, and scientists at Emory University and researchers from collaborative institutions worldwide are leaving no stone unturned in their quest for innovative treatment options. In an exciting breakthrough, researchers at Emory’s NPRC and their colleagues have delved into the intricate world of type 1 Interferon (IFN-I) signaling, a key player in our body’s defense against infections. Their groundbreaking study, conducted with nonhuman primates, offers a fresh perspective on combating SARS-CoV-2, and paves the way for potential new treatments for COVID-19. 

The Defender: Type 1 Interferon 

Senior author, Mirko Paiardini, PhD, and his team focused on understanding the role of IFN-I in SARS-CoV-2 infections. IFN-I is like the first responder in our body’s defense mechanism, acting swiftly to thwart viral replication when an infection is detected. This study, a first in nonhuman primates, sheds light on how tweaking IFN-I signaling can impact viral replication and the progression of COVID-19. 

The Balancing Act: IFN-I’s Double-Edged Sword 

The findings of the Emory University study illuminate a delicate balance in the fight against COVID-19. While early IFN-I responses are crucial for containing SARS-CoV-2, an excess of IFN-I signaling can lead to hyperinflammation in the body, contributing to severe disease. This discovery underscores the importance of timely intervention to prevent excessive inflammation, a primary driver of severe COVID-19 cases. 

Dr. Paiardini, Division Chief of Microbiology and Immunology, Professor of Pathology and Laboratory Medicine, and Co-Director at the Emory Center for AIDS Research, emphasizes the significance of this balance and the need to fine-tune the body’s immune response to combat the virus effectively. 

The Experiment: IFNmod to the Rescue 

Researchers used a modified version of interferon, aptly named IFNmod, in rhesus macaques before and during acute SARS-CoV-2 infection to modulate IFN-I signaling. The results were nothing short of remarkable. IFNmod treatment weakened antiviral and inflammatory gene expression, leading to lower levels of inflammatory cytokines in the lower airways. This reduction in inflammation correlated with reduced lung pathology.  

“We were also surprised to find IFNmod treatment had a profound effect on SARS-CoV-2 viral loads, with a 3,000-fold reduction in viral loads in the lower airways of treated animals,” says co-first author Elise Viox.  

Emory University’s groundbreaking research into modulating type 1 Interferon signaling offers hope in our battle against COVID-19. By striking the delicate balance between immune response and inflammation, we’re closer to effective treatments for this tenacious virus.  

The Influence of Social Status on Early Social Development: Insights from Maturing Visual Pathways

 Forming infant-caregiver bonds is critical to social and neural development during infancy. However, the underlying brain pathways supporting infant attention to others’ eyes have remained largely unknown. Recent groundbreaking research conducted at the Emory National Primate Research Center (EPC) and the Marcus Autism Center sheds light on the development of eye contact behaviors in infant rhesus macaques and their influence on brain growth. This research not only has the potential to reveal early neurobehavioral markers of social disability but also provides insights into the impact of social status on these developmental processes.

“For both humans and macaques, learning to engage with the eyes of others during infancy is a critical social skill in typical neurodevelopment,” says senior author Mar Sanchez, Ph.D. Exploring the brain regions and environmental factors that contribute to this behavior can enhance our understanding of its emergence and role in primates’ social development.

Studying Infant Macaques

The research team conducted a study involving male infant macaques, measuring their eye contact behaviors through eye-tracking tools while showing them videos of other macaques. Resting-state functional MRI (rs-fMRI) scans were also taken to analyze connectivity within the occipital and temporal cortices, which are involved in visual perception and social processing.

The researchers collected data from two weeks to six months old at regular intervals. This unique longitudinal dataset allowed them to observe changes in the connectivity patterns between the occipital and temporal cortices over time. They discovered that the most significant changes occurred during the first three months of life, which is analogous to humans’ first year of life.

Importance of Brain Connectivity and Influence of Social Status

Infants with stronger connections between the brain areas responsible for visual processing (primary visual areas) showed a greater tendency to make eye contact with other monkeys earlier than infants with weaker connections. The study also revealed that social status impacted the relationship between brain maturation and eye contact. Low-ranking infants displayed a stronger association between the development of visual pathways and eye contact compared to their high-ranking counterparts. This suggests that low-ranking infants may have adapted brains that facilitate early identification of faces and expressions, enabling them to navigate social interactions more effectively.

Implications for Human Development

Aiden Ford, the first author and a Ph.D. candidate in Neuroscience at Emory, highlights the influence of social status on the development of the social brain, even in the earliest postnatal months. This research provides unique insights into brain and behavior development dynamics at both the group and individual levels. It also raises the possibility that early exposure to adversity may accelerate biological, brain, and social development.

The research group plans to conduct further studies mapping the development of social behaviors and social brain regions in infant macaques. The amygdala, a critical part of emotional processing, will be a particular focus. Additionally, the effects of infant social status will continue to be investigated, providing a deeper understanding of how social factors shape neural development.