Why we need Non-Human Primate Disease Models-Prisys Biotech

Non-Human Primates Studies

Primates are among the most sophisticated species, where a total of 11 families/51 genera /180 species have been discovered, including monkeys, apes, and the human being. They have the most developed brains in the animal kingdom. In addition to their high intelligence and complex social behavior, in the motion aspect, the extremely flexible thumb renders the ability to grasp things. This finger-to-finger grasp is an exclusive trait almost only for primates, which gives them a various possibility and potential on finger-handling. In term of perception, the primates are the very few species developed an advanced visual system with trichromatic vision (be able to see three colors), while the other mammals rely heavily on olfactory and tactile sensations. This unique trait renders the primates the great ability of object discrimination and perception.

As the name implies, non-human primates are primates other than human beings. Because of having many biological characteristics similar to human beings, they are generally considered very important experimental animals, especially in some research fields that requires higher pathological/physiological similarities, primates are nearly irreplaceable. In the experiments, old World monkeys are recruited more often, and mainly with rhesus and cynomolgus macaque. Because of close phylogenetic relationships, the identical genetic sequence between human and macaque reaches an amazing 93%, in contrast the similarity is only 84% when compare human vs. murine. Therefore, compared with other laboratory animals, non-human primates have a unique advantage during investigation of many human life science dilemmas, such as immunology, brain-mapping, physiological functions, and metabolism etc. In addition to the fundamental research, they are also excellent modeling animals to study the mechanism and treatment of multiple human diseases.

Application of Non-Human Primates in Medical Research

There are more than 70 primate breeding and R&D centers for biomedical research have been established and operating in many countries of the world including the United States, Germany, Japan, New Zealand, South Korea, Thailand, India. In general, those primate centers are stepping on the breaks while the expanding the use of experimental primates, due to the scarcity of resources, cost/budget concerns, and ethical reasons. For instance, research on non-human primates in Europe fell by 28% between 2008 and 2011, and Harvard Medical School had shut down its primate center in the year of 2015. In another hand, along with the rapid development of life science research and translational medicine research, China has become a major player in breeding and using of experimental primates over the past decades. According to official statistics, there are more than 20 experimental monkey breeding facilities along eastern an southern China, and the total inventory is considered has reached over 300,000. This fact has proved that this industry in China will continue to play an important role in the progression and innovation of life science and biomedical industry.

Why we need Non-Human Primate Disease Models – Taking Brain Disease Research as an Example

Currently, there are nearly 1 billion patients with brain diseases worldwide, with an economic burden of about $1 trillion every year. In China, the number of children with autism has reached 1.64 million. About 16 million people are suffering from schizophrenia and more than 26 million are suffering from depression. Remarkably, patient numbers with neurodegenerative diseases are increasing with an incredible rate due to the population aging in China. For example, the number of patients with Alzheimer’s Disease is more than 9 million, and doubled in the past decade; The number of Parkinson's disease patients in China has exceeded 3 million, making China the country with the most patients. At present, the effective treatments for the forementioned brain diseases are scarce and limited. The lack of ideal animal model is an important limitation factor for studying the mechanism behind the brain diseases and the development of novel therapeutics. The widely used murine model has significant limitations, mainly due to the huge differences in the brain structures, functions, and neuron-signaling pathways compare to humans. On the other hand, the complex symptoms of human brain disease are often hard to replicate in mice. Neurodegenerative diseases, such as Alzheimer’s and Parkinson's disease, although a similar cognitive phenotype is present in transgenic mice with human mutations, the commonly seen neuron death in human patients is lacking. This makes it impossible to screen for new drugs targeting this pathway and to alleviate such symptoms in mouse disease models. As a consequence, a large number of drugs tested and worked well in mice have failed in human clinical trials. One of the most influential case is the monoclonal antibody Bapineuzumab, a new anti-Alzheimer’s disease drug, had failed in phase III clinical trials due to no obvious therapeutic effect and presented some adverse reactions such as vascular cerebral edema. Another case is the Alzheimer’s drug candidate, Solanezumab, a monoclonal antibody against Aβ, failed because it had no obvious therapeutic effect. In 2014, an article in Nature wrote: "Misleading Mouse Studies Waste Medical Resources".

An embarrassing fact is while we spent a lot of money and time on brain disease research and new drug development, a lot of those efforts were wrong allocated on rodent disease models or consecutive procedures based on that result. As a comparison, due to the close evolutionary relationship, non-human primates are highly similar to human beings in brain structure, physiological activities and many other aspects, making them the ideal modeling animals for brain diseases. The human disease models in Non-human Primates can better replicate the characteristics of corresponding human diseases, and better simulate the mechanisms and pathologic processes. More importantly, due to its developed central nervous system, non-human primates have complex cognitive and social behaviors as well as sophisticated motion controls, which gives the researchers a great tool to design complicated study designs such as memory tasks. This is particularly important for objective evaluation of core behavioral markers, such as emotional/social cognition, memory, and fine motions. Therefore, the use of non-human primates in brain disease research will greatly reduce the risk of drug discovery, and become the only bridge between fundamental research and clinical assessment.

Why we need Non-Human Primate Disease Models – a few other Examples

1.        Cerebrovascular diseases: The cerebral vascular anatomy of non-human primates is very similar to that of human beings, and the cerebral ischemic infarction model established by non-human primates is an important tool to study the pathogenesis, injury mechanism and prevention and treatment measures of human cerebrovascular diseases.

2.        Reproduction: Non-human primates and humans share many aspects of reproductive biology, such as gametogenesis, fertilization, implantation of embryos in utero and early pregnancy maintenance, and some non-human primate females have menstruation and menopause like humans. With the development of reproductive medicine research, non-human primates are increasingly used in reproductive medicine research.

3.        Orthopaedics: Due to the high degree of homology, non-human primates are also widely used in biomaterials research. Preclinical studies on medical biomaterials in non-human primates can better simulate the biological effects of the materials transplanted into humans.

4.        Ophthalmology: Glaucoma is a common and difficult eye disease with rapid onset and great harmfulness. Primate eyeball structure is highly similar to humans’, which is an ideal animal experimental model of glaucoma.

5.        Transplantation: Non-human primates have a high degree of homology with humans, and a high degree of similarity with humans in anatomical structure and physiological characteristics. Taking non-human primates as the animal model to study organ transplantation can better simulate the problems after clinical surgery, which is of great significance for optimizing surgical methods and exploring new transplantation methods.