The newest possible model to test therapeutics and interventions for neurodegenerative diseases could be a 20-year-old baboon.
Researches have recently discovered that, just like humans, some non-human primates experience age-related cognitive decline. This month, a team at Texas Biomedical Research Institute’s Southwest National Primate Research Center took the first steps in assessing and developing the baboon — the largest non-hominoid primate — as appropriate animal model for laboratory study of early stage Alzheimer’s disease. Research indicates that baboons start to express a decline in cognitive skills at about 20 years old — the equivalent of a 60-year-old human.
Texas Biomed SNPRC associate professor and the lead researcher on the study Dr. Marcel Daadi and colleagues published their findings in a paper titled “Age-related Cognitive Decline in Baboons: Modeling the Prodromal Phase of Alzheimer’s Disease and Related Dementias” in the May issue of the journal Aging. According to Daadi, this is the first time a naturally occurring model for early-stage Alzheimer’s has been reported.
“We don’t know how Alzheimer’s disease starts, and if you are trying to treat a patient already with advanced disease, it is nearly impossible to treat them because of the significant loss in brain cells,” Daadi said in a statement. “If we detect early on pathology in the brain then we can target interventions to prevent it from progressing, and we are in a better position to help.
He added: “This model could be relevant to test promising drugs, to better understand how and why the disease develops and to study the areas of the brain affected in order to determine how can we impact these pathways.”
Lab Rats No More?
To date, the role of go-to laboratory model in the testing of therapeutic interventions for neurodegenerative diseases has been played by various rodent species. But while mice have been integral to a better understanding of neurodegenerative diseases, discoveries that may appear promising in mouse studies don’t often translate in human trials.
Daadi said his team explored the possibility of a baboon model because of primates are much more comparable than rodents to humans in terms of not only cognition but in genetics, physiology, emotion and social behavior — all of which could help shed light on new Alzheimer’s interventions. Humans and nonhuman primates share many similarities, including age-dependent changes in gene expression and a decline in neural and immune functions.
Previous studies have pinpointed the prefrontal cortex of the brain as one of the regions most affected by age, playing an integral role in memory function and in self-regulatory and goal-directed behaviors, all of which are vulnerable to aging. To observe whether these PFC functions are impacted by aging in baboons and to determine whether the baboons at varying ages could discern and learn new tasks, Daadi and his team separated the baboons into two groups based on age — an adult group and an aged group. Then, they performed four different cognitive tests were performed to observe novel learning, motor function and memory and shape association.
“What we found is that aged baboons lagged significantly in performance among all four tests for attention, learning and memory” Daadi said. “The delay or inability to collect rewards — response latency — also increased in older baboons, suggesting a decline in motivation and/or motor skills. The team then used a more complex task requiring integration of several cognitive processes and demonstrated that aged subjects actually have deficiencies in attention, learning and memory. Human studies have suggested a precipitous decline in brain systems function and cognition with 60 years as the potential breakpoint. These findings are consistent with our results.”
Why Do Science Laboratories Still Rely on Animal Testing?
Daadi and team maintain that the baboon model could mean tremendous advances in the research community’s ability to improve our understanding of Alzheimer’s and how to cure or prevent it. Despite that it kills millions of people per year — one in three older adults die of Alzheimer’s or a related form of dementia — the cause is still not known, it has been nearly two decades since the last Alzheimer’s treatment was approved by the FDA, and more than 99 of every 100 experimental therapies does not succeed at transitioning from preclinical study to human clinical trials. “The failure rate in clinical trials of Alzheimer’s disease therapeutics is extremely high at about 99.6 percent,” Daadi said, “and we need to change that.”
While cell cultures, tissue studies or computer models can answer some questions, research with animals remains for the advancement of human health — scientists can only learn so much about complexity of disease processes in a petri dish.
According to the center, 2,500 nonhuman primates — including 1,100 baboons — live on the research campus. Nearly all of them live in groups, spending much of their time playing and grooming in a rich social environment. They also participate in “enrichment programs” designed to help stimulate species-typical behaviors and promote psychological well-being using social, physical, occupational, feeding and sensory enrichment techniques that often mimic natural behaviors seen in the wild.
Organizations like PETA argue that animal cruelty is inherent in animal testing, and that millions of animals suffer and die in experiments at university laboratories.
Meanwhile, they remain central to the study of infectious diseases and of chronic diseases, such as heart disease, diabetes, liver disease, and neurological disorders, providing a resource for scientists across the U.S. Recent studies with premature baboons enabled Texas Biomed researchers to refine the technique of high-frequency oscillatory ventilation, a method now used to save the lives of thousands of premature babies and minimize lung damage in these children, the center reported. Nonhuman primates are have also provided valuable insight into the development of the hepatitis B and C vaccines, Ebola virus, and into the impact of the Zika virus on mothers and children.
“Virtually every major advance in medical knowledge and treatment has involved research using animal models,” the center writes on their website. “Animal research has saved lives, extended life expectancy, and improved the quality of life for both humans and animals by enabling scientists to conduct critical experiments that identified ways to prevent, treat, and cure disease.”
Daadi and his team plan to submit a National Institutes of Health grant to allow for further research on the baboon as a model for Alzheimer’s research. Early detection of age-associated cognitive dysfunction is critical — and it could broaden understanding of the breakdown of brain systems and help lead to better interventions.
“Our next step is to investigate the neuropathologies behind this cognitive decline and perform imaging to understand what happens to the neural connections and determine where defects may be,” he said. “We will also look at biomarkers that can give us an idea of why this steep decline is happening. All this data will enable us to further characterize the baboon as a naturally-occurring model that may prove useful for testing early therapeutic interventions.”