Over the past century, medical science has created vaccines for polio, smallpox, mumps and measles. We have discovered new treatments for infertility, heart disease and diabetes. Our progress in combating leading killers such as AIDS, lung disease and cancer has accelerated. Through stem cell research, we have gained new insights that have the power to transform our understanding of human health and biotechnology. Without animal research, these breakthroughs would never have occurred. The Foundation for Biomedical research's website details the biomedical advances in human and animal healthcare.
Less than five percent of animals used in research are primates, and numerous government agencies and other organizations ensure that testing is humane and efficient. At the ONPRC, we hold ourselves to the highest standards of animal treatment. Our research on primates is vital to our understanding of human health and disease, and we have created models that revolutionize the way we conduct experiments and treat life-threatening disorders.
Primates share 98 percent of their genes with humans. Their body composition, maturation and reproductive processes are virtually identical to ours, giving us the unique ability to safely evaluate and test treatments that can dramatically improve human health. ONPRC researchers use these NHP models to deepen our understanding of disease and immunology—accelerating discovery and reducing the time it takes to bring new treatments, cures and vaccines to fruition.
Aging: Unlocking the secrets to a long and healthy life.
Over the past century, the average life expectancy of Americans increased by three decades. Forecasters predict that, by 2050, the elderly population will outnumber younger people for the first time in history. This rise in our aging population is placing an increasing demand on our health care system—driving scientists to rapidly develop new treatments for age-related conditions like osteoporosis, cancer and Alzheimer’s disease.
Because of their genetic similarity to humans, ONPRC scientists use rhesus macaques to explore the effects of aging. With the care and attention given to our primates—which rarely survive into old age in the wild—we can extend their lifespan beyond thirty years. This lets us closely examine the causes of normal and pathological aging and leads us into creating new cures and therapies.
We’ve developed new, non-invasive technologies like bone densitometry, magnetic resonance imaging and remote activity measurements to let us closely monitor changes in cognition, sleep, behavior and other physiological functions. We are discovering how hormones can aid in cognitive and emotional health. Our latest studies are helping us understand how diet modification can help hinder age-related declines in immune function, learning and memory.
Our cross-disciplinary approach ensures that we are making the most effective use of our valuable animal resources and gives us the ability to reveal the important interrelated mechanisms that underlie human aging. Through our research, we hope to redefine “old age” and enable everyone to lead long, healthy lives.
Stopping the HIV epidemic remains one of the top global health priorities. Since the beginning of the epidemic, the World Health Organization (WHO) estimates that more than 70 million people have been infected with HIV and about 35 million people have died. At the end of 2017, an estimated 36.9 million people were living with HIV due to continued new infections and individuals living longer due to greater access to antiretroviral treatment. Highly active antiretroviral therapy (HAART) limits HIV replication, which subsequently improves health and prolongs the life of HIV-infected individuals. However, HAART is not curative and does not eliminate the virus from the body. HAART cessation is invariably followed by rapid recrudescence of viral replication and progression to AIDS in all but the rarest of cases. Thus, HAART requires lifelong adherence, which many patients find challenging due to side effects, need for strict adherence, resistance, stigma and cost. Because of these limitations, a safe and effective vaccine remains the best hope of controlling the HIV epidemic.
Rhesus macaques develop a disease that closely mimics human acquired immunodeficiency syndrome (AIDS) when infected by simian immunodeficiency virus (SIV) or chimeric simian-human immunodeficiency viruses (SHIV), and represents the best animal model for HIV infection. Given the remarkable similarity of the immune systems of macaques and humans, preclinical vaccine development is heavily dependent on the SIV and SHIV macaque models.
At the ONPRC, we study the immune response to HIV infection using these valuable animal models. Scientists at the Center are at the forefront of those discoveries, learning how both antibodies and killer T cells contribute to control and how these immune responses might be best generated by vaccination. Although a fully effective vaccine is still years away, we are making great strides toward defining the kinds of vaccines that can work to help control or prevent infection.
In addition to HIV vaccine development, a curative approach for HIV infection is now recognized as both a necessary and attainable goal. Indeed, the International AIDS Society Working Group on HIV Cure recently set forth seven key scientific priorities for HIV cure research, one of which was the identification of anatomical and cellular sources of viral persistence in physiologically relevant animal models such as SIV-infected rhesus macaques. At the ONPRC, we are answering this call by defining viral reservoirs during HAART and designing novel approaches to eradicate the virus.
Depression: Individual treatment, global progress.
Forty million Americans will suffer from depression during their lifetime, and ten percent of pregnancies develop into the debilitating condition known as post-partum depression. Left untreated, these disorders can disrupt a person’s ability to function, compromise their immunity and wreak havoc on their families’ lives.
But to develop effective treatments, we must first understand the causes.
That’s why researchers at the ONPRC are tapping into the early triggers of anxiety and depression. By investigating the interplay between genetic and environmental factors, we can create breakthrough medicines and therapies that help children and adults across the world.
ONPRC scientists are making constant progress in uncovering the mechanisms of the human brain. We are examining the possible links between post-partum depression and estrogen levels, how hormones predispose infants to depression and anxiety, and what effects serotonin levels have on behavior and mood.
These advances are changing the way we assess and handle these conditions—taking us closer to treatments that are tailor-made to specific causes and reducing the potential for negative side-effects.
Infectious diseases in the 21st century
The World Health Organization (WHO) estimates that infectious disease is responsible for 20% of all deaths worldwide and that this number is likely to be even larger if certain cancers, cardiovascular and respiratory/ digestive deaths, which can also be attributed to infection, are included. Interestingly, six diseases account for 90% of infectious disease deaths, and include acute respiratory infections (including pneumonia and influenza), AIDS and AIDS-associated disease, diarrheal diseases, tuberculosis, malaria and measles.
To curb these growing global problems, further elucidation of host-pathogen interactions is absolutely needed to better design therapeutics and vaccines to prevent morbidity and mortality from existing and newly emerging infectious pathogens. Commensurate with this need is the absolute requirement for animal models that parallel and share developmental, physiological and evolutionary relationships with humans, and are susceptible to the same or closely related infectious agents with similar, if not identical, disease sequelae.
Research within the Division of Pathobiology and Immunology is focused on tackling key infectious and chronic diseases that afflict mankind, and include an emphasis on:
A. NHP Infectious and Chronic Disease Model and Assay Development
a. Allogeneic hematopoietic stem cell transplantation (HSCT) model
b. HBV model
c. IBD model
B. AIDS Pathogenesis, Persistence and Vaccine Development
a. RhCMV-SIV vaccine
b. Mechanisms of chronic inflammation/immune activation
c. Host-pathogen interactions
d. HIV cure
e. Adjunctive therapeutic interventions
C. Cytomegalovirus (CMV) Research Program
a. RhCMV-Mtb vaccine
b. RhCMV-Malaria vaccine
D. Models of Emerging Infectious Diseases
a. Zika virus (ZIKV) model
b. Anti-viral drug development
c. Chikungunya virus (CHIKV) model
Assessing the risk and consequences of addiction.
Our research program addresses alcohol and nicotine addiction, two of the three leading causes of preventable death in the USA, as well as emerging efforts in cannabinoid addiction. The program utilizes the propensity of NHPs to self-administer psychoactive substances in a repeated manner that recapitulates addictive disorders in humans. Our program is organized to identify key endocrine aspects of the risk for heavy alcohol drinking, particularly as related to the stress-axis response, menstrual cycle quality and immune system regulation. We can identify the specific brain changes associated with the transition from low and moderate use of a psychoactive substance (alcohol, nicotine, cannabinoids) to the development of dependence. We also explore a genetic basis of nicotine and alcohol comorbidity by focusing on genes specific to risk for smoking in humans that also occur in monkeys. Our program is able to assess the effects of in utero exposure to alcohol, and nicotine on fetal brain growth using in vivo MRI imaging. Finally, we are able to test interventions that may decrease addictive alcohol drinking and alcohol/nicotine co-morbidity in partnership with pharmaceutical companies.
This year, an estimated one million infants will be exposed to addictive drugs. This figure continues to rise, and with it, the tragic effects. Children born to substance-abusing mothers are often addicts at birth, suffering withdrawal symptoms like seizures, vomiting and breathing problems. Alcohol leads to deformation and irreversible brain damage; nicotine use can rob a child of healthy lungs for life and increase risk of ADD and obesity. With recent trends in legalization, there is a growing and unknown consequence of in utero exposure to cannabinoids and marijuana. Perhaps we can’t prevent maternal substance abuse. But we can help protect the children who suffer the consequences. Scientists at ONPRC are leading the way in developing technologies that combat both the addiction and the negative effects of maternal addiction on their infants. We have created models that reproduce the changes in fetal brain and lung development seen in affected human infants. Our discoveries have led to new therapeutic approaches that lessen effects of maternal drug use on the unborn. With these innovative breakthroughs, we can give desperately needed help to those most at risk—and least capable of caring for themselves.
Obesity and diabetes are twin epidemics with global impact on public health.
One out of three Americans is obese, and two thirds are overweight. Type-2 diabetes—thought to result from over-nutrition and lack of exercise—is rising at an alarming rate. Recently, scientists have linked diabetes and other metabolic disorders to an increased risk for immune disorders, renal failure, heart disease and cancer.
Once thought to be a problem mainly of the developed world, the rates of metabolic disease are rising worldwide, and the extent of obesity in Africa is now greater than that of undernutrition.
The modern Western diet is the leading contributor to these severe metabolic conditions. Characterized by an over-consumption of energy-dense foods, the way we eat leads to an increase in adipose tissue, resulting in insulin resistance, metabolic syndrome and diabetes. Once these conditions arise, they are difficult, if not impossible, to reverse.
The ONPRC has developed a high-fat diet-induced obesity model in rhesus macaques that allows us to understand the full spectrum of obesity-related complications. With this innovative model, scientists can study the progression of obesity, isolate the early signs of its related conditions, and determine how to best treat and prevent this serious disease and its consequences.
Reproductive health: Improving fertility, preserving species, and preventing unwanted pregnancies.
More than six billion people populate the planet—millions of whom lack access to adequate health care. Resources in developing countries are becoming scarcer, leading to increased malnutrition, child mortality and the spread of disease. And in industrialized nations, infertility is rising and biodiversity is shrinking at an alarming rate.
It is no wonder reproductive health is a primary global concern.
Researchers at the ONPRC are pioneering ways in which we can treat infertility and create safer, more effective contraceptives. We are advancing assisted reproductive technologies that will help families overcome infertility, and developing early detection mechanisms that can help prevent pregnancy-related disorders. Our heightened understanding also helps conservationists create new contraceptive and breeding strategies to preserve species on the brink of extinction.
Reproductive research is a primary mission of the ONPRC and our success hinges on the study of primate anatomy and physiology. Because of their considerable similarities to humans, including menstrual cycles and neonatal development, we can unravel the mysteries of reproductive systems and address the critical issues of reproductive health.
Stem cells: Harnessing the regenerative power of the body.
The devastation of Alzheimer's, Parkinson's, and Lou Gehrig's disease spreads far beyond the individual who suffers from these and other neurodegenerative human conditions. As of yet, these disorders are incurable—rendering families and victims helpless to endure the inevitable degeneration of the brain and nervous system. But there is hope. With the regenerative power of stem cells, we have the potential to reverse this fate.
Despite controversies and funding limitations, embryonic stem cell research has significantly enhanced our understanding of systems at the cellular level. These "master" cells of the human body are capable of becoming an unlimited source of cell and tissue types, providing a possible cure for many conditions.
The greatest challenge in stem cell replacement therapy has been immune-response rejection of transplanted cells. Because stem cells can only be extracted from early embryos, sometimes the human body will attack the genetically dissimilar transplants. That's why researchers at the ONPRC are creating innovative ways of allowing introduced stem cells to avoid rejection.
Nearly every cell in the human body contains the complete set of genes needed to create a fully functional adult. Using a method called somatic cell nuclear transfer, ONPRC scientists have managed to coax a skin cell to revert back to its embryonic state. This breakthrough means that scientists may be able to one day develop nerve, heart, liver, and other cells that originate from the patient—and avoid the risk of immune system rejection.
Mitochondrial disease caused by pathogenic germline mitochondrial gene (mtDNA) mutations is maternally transmitted through oocyte. The resulting loss of cellular respiration leads to severe and progressive disorders, involving several different organs with prominent involvement of the central nervous system, cardiac and other vital organs. ONPRC scientists developed mitochondrial replacement therapies (MRT) that could prevent transmission of mtDNA defects from mothers to their children. Preclinical and clinical studies demonstrated feasibility, efficacy and long-term safety of MRT approaches. Clinical applications of MRT have been recently approved in the UK and currently under consideration in USA.
The advances at the ONPRC are accelerating research in this field, taking us closer to treatments and cures for some of the most common human diseases.