Microsoft word - research at the primate center.docx

Research at the primate center spans a broad spectrum of human health issues, ranging from asthma to Alzheimer’s, and HIV to
stem cell therapies. Because of the close similarities to humans in both their physiology and behavior, nonhuman primates are
critical models in the development of advancements in human medicine. CNPRC researchers are engaged in research projects
that are making valuable discoveries, not only furthering our understanding of the basic science behind disease, but in finding
specific treatments and new therapies to prevent, reverse, or cure serious human health problems.
Frequently-used anti-HIV drugs began with studies at CNPRC
The CNPRC’s Infectious Diseases (ID) Unit has been developing the SIV/rhesus macaque pediatric model of disease for many
years, and successfully testing drug therapies used to prevent the transmission of HIV from mother to infant. Researchers in the
ID Unit demonstrated the safety and efficacy of the anti-HIV drug known as zidovudine (AZT) in infant monkeys in the early
1990’s. Having been safely tested in monkeys and successfully proven in human clinical trials, AZT protects millions of human
infants around the world from infection with HIV. The CNPRC was also the first to demonstrate that another anti-HIV
medication, Tenofovir (PMPA), was effective in treating animals that were already infected with SIV, thus leading to human
clinical trials in HIV-infected people. Tenofovir is now the most widely used anti-HIV drug in the world, with use in over 100
countries worldwide, including the U.S., the European Community, Cambodia, South Africa, and Latin America.
Gene therapy treatment for Alzheimer’s
Because of groundbreaking research performed at the primate center in the Brain, Mind, and Behavior (BMB) Unit, patients with
mild Alzheimer’s Disease (AD) can now receive a targeted gene therapy that restores brain function to levels seen before the
disease damaged their brain neurons. This treatment was developed from research at the CNPRC over the course of 12 years in
collaboration between UC San Diego and CNPRC research scientists. Studies in aged macaques at the primate center
demonstrated that this therapy restores the volume and receptor function of cholinergic neurons to levels observed in younger
animals. In 2001, the FDA approved Phase I clinical trials, the first step in transitioning a new treatment or medication from
animal studies to human medicine. The treatment developed by this research – which is the most successful to date – delivers a
natural brain-survival molecule called nerve growth factor (NGF) directly to the dying cells in the brain, restoring brain cells and
alleviating symptoms associated with AD. In early 2009, a Phase II clinical trial began using a higher dose of NGF, and a
potentially more effective treatment for advanced forms of the disease.
Current research is investigating the neuroprotective effects of brain-derived neurotrophic factor (BDNF) in nonhuman primates.
BDNF is effective at reversing neuronal atrophy and ameliorating age-related cognitive impairment. The therapeutic use of
BDNF is being explored as potentially another therapy in reversing the effects of Alzheimer’s disease. Continuing studies are
aimed towards effective treatments for more severe forms of AD as well as amylotrophic lateral sclerosis, Parkinson’s Disease,
Huntington’s Disease, and other neurodegenerative disorders.
Regenerative Medicine research is leading to new cures for human adult and pediatric diseases
The Reproductive Sciences and Regenerative Medicine (RSRM) Unit is actively working towards accelerating new stem and
progenitor cell findings at the basic science level through translation and into preclinical development in the monkey for the
treatment of human diseases. Targeting critical gaps that currently delay new therapies from reaching patients is a major focus of
the research, and includes new predictive models, new imaging tools, and novel studies that address efficacy and safety. For
example, recent investigations in the Center of Excellence in Translational Human Stem Cell Research have shown that cells
important for the vascular system decline significantly with advancing age, and that the consequence of this loss is an absence of
new vessel formation.
Collaborations with Center of Excellence colleagues have also identified new progenitor cell populations in fetal health and
disease, including renal precursors that are currently being used for regenerative potential in the monkey model of obstructive
renal disease. These studies are driven by this established model that fully recapitulates the human clinical condition of fetal
urinary tract obstruction, which is one of the most important conditions affecting young children with kidney disease. This model
allows investigators to compare regenerative capabilities of new stem and progenitor cell populations recently identified in the
Center of Excellence, which once fully assessed, could help eliminate the need for dialysis or whole organ transplantation in a
select population of infants and children.
Link found between temperament and asthma
Recent collaboration between scientists in the Brain, Mind, and Behavior Unit and the Respiratory Diseases Unit has led to
furthering our understanding of how temperament affects health. Data analyzed from the extensive database in the CNPRC
BioBehavioral Assessment (BBA) program shows that early life temperament of rhesus monkeys can very accurately predict
whether or not the animal will develop respiratory symptoms that are related to asthma later in life. This research could lead to
screening young children for the propensity to develop lung disease, and possibly treating them with preventative medications.

Improved understanding of Helicobacter infections
Research in the Infectious Diseases Unit is being conducted using the monkey model to further our understanding of
Helicobacter pylori, a bacterium that infects the stomach of approximately 50% of the human population and causes peptic ulcer
disease and stomach cancer.
Recent studies at the CNPRC have characterized the effects of H. pylori on the response of the gastric epithelium to H. pylori
infection. These studies have demonstrated that early in H. pylori infection there is a dramatic reduction in gastric mucin
oligosaccharides, sugars that decorate mucins, which are the major protein component of mucus lining the stomach. At the same
time, there is a dramatic increase in expression of host antimicrobial molecules, especially beta defensin 2 and other innate
immune effectors. While neither the mechanism of these changes nor their role in disease is yet understood, the scientists have
hypothesized that they are induced by the bacterium in order to promote colonization and persistent infection.
Surprisingly, recent studies suggest that H. pylori infection may sometimes be beneficial. For example, there is epidemiologic
evidence that people infected with H. pylori may be at reduced risk for the development of asthma, and may also be protected
from tuberculosis.
New findings on causes of autism
Other studies in the BMB Unit with exciting results in nonhuman primates are research projects on the causes and biology of
autism. In February of 2008, colleagues at the UC Davis M.I.N.D. Institute reported on an interesting finding that started with the
observation of a link between women that were infected with influenza virus during pregnancy and their child later developing
autism. Tests at the primate center resulted in a confirmation of the researchers’ suspicions – maternal antibodies can cause
infants to display autistic-like stereotypies and hyperactivity, similar to a form of autism in humans. These nonhuman primate
study results have important implications for many aspects of women’s and children’s health and prenatal care protocols.
New imaging techniques have direct application for use in humans
Studies by the Reproductive Sciences and Regenerative Medicine (RSRM) Unit have revolutionized the ability to monitor
transplant efficiency for blood-related disorders and cell trafficking in young monkeys using in vivo imaging including positron
emission tomography (PET), providing new ways to compare and contrast outcomes when different cell sources are used for
transplantation. These new imaging technologies have also effectively demonstrated for the first time engrafted foci of blood-
related stem and progenitor cells at anatomical sites not previously appreciated, which has a direct application to human
transplantation. Techniques and models developed are also being applied by disease teams focused on cell-based therapies for
liver disorders and neurodegenerative conditions such as Huntington’s Disease. Once safety is shown in these studies clinical
trials will be conducted at the UC Davis Medical Center in the Institute for Regenerative Cures with the assistance of the Clinical
and Translational Science Center.

Secondhand smoke has health effects far beyond what was previously thought
Investigators at the CNPRC have linked prenatal and neonatal Environmental (i.e. secondhand) Tobacco Smoke (ETS) exposure
with adverse effects on lung development and immune responses, and an increased susceptibility to infection and childhood
asthma. Studies in this Respiratory Diseases laboratory have also addressed the controversy of whether ETS exposure during
pregnancy can cause the same neurobiological damage as smoking during pregnancy. Research has answered this question by
demonstrating that prenatal ETS exposure can have adverse effects on lung development, a negative impact on cognitive
function, and an alteration of the brain synapses similar to the known effects of nicotine on brain development.
Antimicrobial soaps shown to be potentially harmful to reproductive health
CNPRC research in the RSRM Unit, has demonstrated that a common antibacterial chemical added to soaps, washes, lotions,
wipes, and detergents can alter hormonal activity leading to many health problems, including cancer, reproductive failure, and
developmental abnormalities. This study demonstrated the negative effects of the widely used antibacterial compound
triclocarban (TCC), used for more than 45 years in the U.S. and Europe. In addition to studies with TCC, a series of
investigations has been conducted to address other “endocrine disruptors” and reproductive toxicants. Some of these compounds
include dibutyl phthalate, used in nail polish and children’s toys; and bromodichloromethane, a byproduct of adding chlorine to
drinking water, which can enter a person’s system from chlorinated water by breathing the vapors (e.g., during cooking), or
directly through the skin in a swimming pool, washing dishes, or bathing.
Solutions to many human health problems
Many other ongoing studies at the CNPRC have far reaching implications for human health. Some examples include: utilizing
preclinical monkey models to assess new gene therapy applications for the treatment of diseases such as adenosine deaminase deficiency, a life-threatening inherited condition that results in severe combined immune deficiency; sickle cell disease; muscular dystrophy; and HIV/AIDS lymphoma, which have been instrumental in supporting new human clinical trials; programs exploring the neurobiology of cognitive aging; studies on the role of psychosocial stress on disease progression in SIV infected macaques, including the additive consequences of methamphetamines, which affect a major stress response system; investigating the physiological changes associated with fructose and other dietary sugars, the role of these sugars in our diet and the link with metabolic imbalances that may lead to an increase in obesity and diabetes; and establishing a nonhuman primate diabetic model with the goal of someday eliminating the need for insulin injections. These and many other important ongoing research projects are leading to vast improvements in human health and the elimination of life-threatening diseases that affect millions of people worldwide.  


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