Asthma, a prevalent chronic lung condition affecting millions worldwide, remains a significant health concern. However, recent breakthroughs in research conducted at the California National Primate Research Center (CNPRC) offer hope for a deeper understanding of the disease and potential avenues for treatment. 

Insights from CNPRC’s Inhalation Exposure Core 

The CNPRC’s Inhalation Exposure Core provides a unique platform for investigating the environmental influences on asthma development. Due to its location in Northern California, where wildfire smoke and air pollution can occur, this facility is instrumental in studying mechanistic and therapeutic aspects of lung diseases. Collaborating with experts from the CNPRC Cardiorespiratory Diseases Unit, researchers explore asthma’s origins in both children and adults, crucial for developing effective treatment strategies. 

As of now, there isn’t a cure for asthma, but progress continues to be made through research and there are treatments available to help manage and control its symptoms. Lisa Miller, head of CNPRC’s Inhalation Exposure Core, emphasizes the importance of nonhuman primate models in asthma research, offering insights into the disease across different stages of life. 

Understanding Asthma Variability 

Asthma is characterized by airway sensitivity to environmental triggers, which can lead to restricted breathing and potentially fatal consequences if untreated. The disease varies among patients, with some, particularly adult females, experiencing non-allergen induced asthma resistant to standard treatments.  

A recently developed nonhuman primate model of non-atopic asthma mirrors human conditions and could offer significant benefits to approximately 7.5 million Americans. Rhesus macaques can naturally exhibit airway hyperreactivity akin to non-allergen induced asthma, making this model remarkably reproducible and valuable for research purposes. 

Early Behavior, Later Breathing 

A unique longitudinal study conducted at CNPRC, known as the biobehavioral assessment program (BBA), revealed intriguing connections between infant behavior and later asthma development. Behavioral inhibition, a temperament defined by fearful responses to novelty, in infancy correlated with airway hyperreactivity in juveniles and adults, highlighting the interplay between behavior and health outcomes.  

CNPRC researchers discovered a link between behavioral inhibition in infancy and the development of asthma phenotypes. They conducted a study involving 49 rhesus macaque monkeys, tracking their development from infancy to yearling status. Of these monkeys, 24 exhibited behavioral inhibition during infancy and later showed airway hyperresponsivity as juveniles. 

The Right Resources for Research 

CNPRC’s Inhalation Exposure Core, comprising expert scientists and advanced facilities, is pivotal in testing potential asthma treatments and airway hyperreactivity, either naturally in non-atopic asthma or in response to toxic inhalants such as the pollutant ozone (O3).  

Recent studies, including one involving a novel drug derived from flaxseed, showcased promising results in preventing immune changes related to asthma symptoms and help assess whether the non-atopic asthma monkey model would be sensitive to novel antioxidant compounds. 

Results revealed specific immune changes caused by O3 exposure, and the treatment successfully prevented immune changes associated with asthma symptoms. Consequently, the drug tested in the rhesus macaque model of non-atopic asthma is now slated for clinical trials in human asthmatics. 

Further Exploration 

As asthma manifests in various forms and developmental stages, the rhesus monkey model remains crucial for developing and testing new therapies. The CNPRC’s Inhalation Exposure Core stands as a beacon of hope in translational cardiorespiratory disease research, offering invaluable insights with global implications. 

In conclusion, the ongoing research at CNPRC not only unveils a reproducible animal model of human asthma but also underscores the intricate relationship between behavior, personality, and health. These findings pave the way for further exploration into asthma’s complexities and the development of targeted interventions, offering hope for asthma patients worldwide. 

Recent research conducted at the California National Primate Research Center (CNPRC) has uncovered fascinating insights into the perception of touch in nonhuman primates, shedding light on how our brains process pleasurable sensations. Led by Ph.D. Candidate Joey Charbonneau and CNPRC core scientist Eliza Bliss-Moreau, the study investigates the neural responses to gentle, pleasurable touch. Given that the animals were anesthetized, researchers were surprised to find that the brain activity in monkeys mirrored that of humans experiencing pleasant touch. 

Published in the Proceedings of the National Academy of Sciences, the study unveils age-related differences in touch perception, sparking intriguing questions about consciousness and the brain’s processing of tactile stimuli. Understanding these mechanisms not only illuminates fundamental aspects of neuroscience but also has implications for various human conditions, from autism spectrum disorder to neurodegenerative diseases like Alzheimer’s. 

Using functional magnetic resonance imaging (fMRI), researchers examined the brain activity of monkeys who were anesthetized in response to slow, pleasurable touch (also known as affective touch) and faster, discriminative touch (referred to as discriminative touch). Remarkably, they found that the same brain regions activated from pleasurable touch in awake humans and monkeys who were not awake. This suggests that the rewarding aspects of affective suggests that touch transcend species boundaries and do not necessarily require consciousness. 

Moreover, the study identified age-related changes in how touch is represented in the brain, particularly in regions associated with affective processing. Older monkeys exhibited alterations in brain activity patterns to discriminative but not affective touch, highlighting the importance of considering age-related factors in understanding touch perception. 

Nonhuman primates serve as invaluable models for studying touch perception, offering insights that could inform additional research. By leveraging this model, researchers aim to understand the mechanisms underlying touch perception across the lifespan and develop interventions for age-related diseases impacting affective processing. 

This pioneering work, supported by the National Institute of Health and other funding sources, represents a crucial step toward unraveling the mysteries of touch perception and its implications for human health and well-being. 

Scientists at Emory University have made an exciting discovery that could bring us one step closer to curing HIV. Their research, published in Nature Immunology, focuses on a special type of immune cell called CD8+ T cells. 

What’s the big deal?
The researchers identified a unique subset of CD8+ T cells in lymph nodes that are particularly effective at fighting simian immunodeficiency virus (SIV), which is similar to HIV in humans. These cells, called TCF1+CD39+CD8+ T cells, work differently from typical T cells but pack a powerful punch against the virus. 

Why is this important?
“Harnessing CD8+ T cell functions is imperative toward an HIV cure,” says Mirko Paiardini, PhD, Microbiology and Immunology division chief at the Emory National Primate Research Center. Currently, 39 million people worldwide live with HIV, and while existing treatments are effective in blocking the replication of the virus, they don’t eliminate the virus completely. 

How do these special T cells work?
These newly discovered T cells are unique because they: 

• Are better at controlling the virus 

• Reduce viral reservoirs (cells and places where the virus hides in the body) 

• Can maintain their effectiveness without getting “exhausted” 

• Have features that allow them to keep reproducing and fighting 

What’s next?
The Emory team plans to: 

• Study these T cells at different stages of infection 

• Explore how well they respond to potential HIV cure treatments 

• Investigate their effectiveness in other parts of the body beyond lymph nodes 

The bigger picture:
This research is part of a larger effort called ERASE HIV, which aims to develop innovative therapies to eliminate or control HIV without the need for lifelong medication. The team is also working with community organizations to share their findings and progress with those affected by HIV.  

While there’s still much work to be done, this discovery offers new hope in the ongoing battle against HIV and brings us closer to the possibility of a cure. 

The human immunodeficiency virus (HIV) remains a formidable challenge for medical researchers worldwide. While antiretroviral therapy (ART) has allowed individuals to manage HIV as a chronic condition and significantly improve their quality of life, certain aspects of the virus’s behavior still elude full comprehension. Among these mysteries lies the infiltration of HIV into the brain, a phenomenon with profound implications for individuals living with the virus. 

A groundbreaking study conducted at the California National Primate Research Center (CNPRC) is shedding new light on this intricate process. Led by Smita Iyer, an Associate Professor in the Division of Experimental and Translational Pathology at the University of Pittsburgh School of Medicine, led the study during her tenure as a CNPRC core scientist. The research offers insights into how HIV spreads within neural tissue and its implications for HIV-associated neurodegenerative disorders (HAND). 

Published in December 2023 in PLoS Pathogens, the study utilized nonhuman primate models to map the immune response to HIV in the brain. By focusing on immune cells known as CD4 T cells, the researchers uncovered the virus’s ability to penetrate neural tissue, thus highlighting its role in HAND. 

The significance of this research extends beyond HIV alone. As many individuals experienced with the cognitive impairments associated with COVID-19 can attest, viral invasion of the brain can have profound and enduring consequences. Nonhuman primate models, like those utilized at CNPRC, are instrumental in unraveling the mechanisms by which viruses breach the blood-brain barrier and persist within the central nervous system. 

Despite the success of ART in suppressing HIV replication in the bloodstream, some patients continue to experience chronic inflammation in the central nervous system. Known as Neuro-HIV, this condition underscores the virus’s unique ability to infiltrate the brain, disrupting neural function and potentially leading to cognitive decline. 

The CNPRC’s pioneering work in HIV and ART research has paved the way for advancements in understanding and combating the virus. From developing the simian immunodeficiency virus (SIV) model to conducting safety testing for crucial antiretroviral drugs, CNPRC’s contributions have been instrumental in the fight against HIV. 

Iyer’s study represents a continuation of CNPRC’s legacy, leveraging state-of-the-art technologies to track the progression of HIV within brain tissue. By elucidating the role of CD4 T cells in facilitating viral entry into the brain, the research provides valuable insights into the pathogenesis of Neuro-HIV. 

The findings of the study challenge conventional wisdom regarding the role of CD4 T cells in the body’s immune response to HIV. Rather than acting as guardians against viral invasion, these cells appear to serve as unwitting accomplices, aiding the virus in spreading throughout the body, including the brain. 

Looking ahead, Iyer and her team are focused on unraveling the complex interplay between different subsets of CD4 T cells during long-term HIV infection.  

By deciphering these intricate mechanisms, researchers aim to gain a deeper understanding of HIV’s impact on the central nervous system and develop targeted interventions to mitigate its effects. As they piece together the puzzle of Neuro-HIV, the quest for effective treatments and ultimately a cure continues unabated. 

Research in nonhuman primates is opening new possibilities for testing treatments for early-stage Alzheimer’s disease and similar conditions before extensive brain cell death and dementia set in. A recent study published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association reveals a six-month window during which disease progression can be tracked and treatments tested in rhesus macaques. 

“This is a very powerful translational model to test interventions that target the tau protein,” said John H. Morrison, professor of neurology at the University of California, Davis, and California National Primate Research Center, and corresponding author on the paper. 

 The Role of Tau Protein in Alzheimer’s Disease 

The tau protein, found in neurons, is implicated in Alzheimer’s disease, frontotemporal dementia, and other dementias. Misfolded tau disrupts essential brain cell functions, spreading through connected regions of the cortex that are crucial for memory and cognition. This leads to an inflammatory response and eventually neuron death. 

Advances in brain imaging, biomarkers in human serum and cerebrospinal fluid, and rodent models have improved our understanding of early-stage Alzheimer’s. However, the relationship between tau, inflammation, and disease progression remains complex. The macaque model bridges the gap between mouse models and human patients, better representing the disease’s progression. 

The Six-Month Window for Disease Progression 

In the study, researchers injected a vector carrying DNA for two mutated tau proteins into the entorhinal cortex of 12 monkeys. This brain region, involved with memory, is where Alzheimer’s typically originates in humans. Over six months, they tracked the spread of tau protein, affected cells, and inflammation using PET and MRI imaging, biomarkers, and microscopy. 

The results indicate a window of at least two to six months where disease progress can be measured, allowing for preclinical testing of interventions targeting the tau protein. “We can look at drugs targeting early-stage Alzheimer’s before dementia develops,” Morrison said. “It’s all about early intervention to arrest progression.” 

This study builds on earlier work at the CNPRC establishing the nonhuman primate model. Future research will combine the tau model with existing systems based on amyloid, further enhancing our understanding and treatment of Alzheimer’s disease. 

In a significant stride toward protecting mothers and their babies, researchers at Tulane University have unveiled groundbreaking findings: mothers with prior exposure to Cytomegalovirus are far less likely to transmit it to their baby, a virus known to cause miscarriages and birth defects. This discovery paves the way for the development of a potential vaccine to safeguard pregnant women and their babies. 

Cytomegalovirus (CMV), a prevalent herpesvirus often contracted unknowingly before childbearing age, typically poses no threat. However, during pregnancy, transmission to the developing fetus can lead to miscarriage, cerebral palsy, and hearing loss. 

While it has long been understood that women facing their first CMV infection during pregnancy are at heightened risk, the protective mechanisms for those previously exposed to the virus remained elusive. 

The study, published in PLOS Pathogens, conducted at the Tulane National Primate Research Center, utilized a nonhuman primate model closely mirroring human CMV infection. Researchers found that when pregnant mothers were initially infected with CMV during the first trimester, transmission to offspring occurred in all cases, resulting in a high rate of miscarriage. 

However, when nonhuman primates with prior CMV exposure were reinfected during pregnancy, their offspring were shielded. A robust immune response in mothers upon reinfection drastically reduced transmission through the placenta, with only one out of five mothers passing the virus to their infants, and no adverse health outcomes observed in any of the offspring. 

Dr. Amitinder Kaur, principal investigator and professor of microbiology and immunology, emphasizes the importance of understanding pre-existing immunity in preventing CMV transmission during pregnancy. This knowledge, she says, is pivotal for the development of an effective CMV vaccine, essential for safeguarding pregnant women and their unborn babies. 

The study’s findings underscore the significance of CMV immunity before pregnancy, as it enables the maternal immune system to shield the baby from congenital CMV transmission if reinfection occurs during gestation. This research holds immense promise for the development of a CMV vaccine, particularly vital in regions with a high prevalence of CMV infections among pregnant women. 

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.