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Our fields of research

Biomedical research forms the basis for the development of new medications – medications that may help us eradicate the serious diseases from which people may suffer. Please find below an overview of our fields of research and achievements.

RESEARCH FOCUSING ON NEW MEDICATIONS, VACCINES AND EXPERTISE

Research on alternative methods

  • In vitro technology

    In vitro technology

    Everyone wants to reduce the number of studies requiring animal testing. We do, too. However, this is not an easy thing to do. For this reason, we are conducting a lot of research on alternative testing methods, guided by the principle of the=three Rs: Reduction, Refinement and Replacement.

    BPRC promotes and supports the application of alternative methods at each of its individual research departments. In addition, we have a dedicated Alternative Methods unit, which is fully devoted to finding alternative solutions.

    The experiments conducted by our Alternative Methods unit

    This unit has designed and characterised a large number of cell culture methods. These methods allow researchers to perform tests on relevant cells in a culture system, before even performing any animal testing. Such ‘pre in vivo tests’ significantly reduce the number of experiments involving experimental animals. What is important here is that we often use the remains of animals who have died to cultivate cells. In this way, the end of one experiment constitutes the beginning of another experiment.

    The work we do

    One of our other objectives is to refine animal testing by reducing the amount of discomfort experienced by the animals. For instance, we focus on the use of adjuvants. Adjuvants are components of vaccines that activate the immune system. Unfortunately, some of the most powerful adjuvants used in animal testing cause adverse reactions, such as inflammation of the skin. One of our fields of research focuses on the development of new adjuvants without side-effects. To this end, we have developed testing techniques that do not involve any animal testing, which are often used by our researchers. We have developed an adjuvant of our own whose efficacy is currently being tested.

    Our challenges

    Cell culture methods are obvious alternatives to animal testing. However, in actual practice, these methods do not always work out. For instance, long-lived cell lines are only suited to particular research questions. This is because these cell lines are generally immortal, tend to be derived from tumours and are therefore different from regular cells. Primary cell cultures are less long lived, meaning we have to start from scratch more regularly. However, they do provide a much more reliable picture of a regular situation than do cell lines. Perhaps stem cell technology will in future help us establish long-lived cell culture systems.
    Another challenge we must address is how to convert the results we have obtained in the lab into methods that can be applied to humans and animals. Validation procedures require that we sometimes use animals.

    Why we continue to need monkeys for research purposes

    To this day, clinical trials cannot be held without prior animal testing. Cell cultures predict how cells may respond. However, it is quite a stretch to predict on this basis how a complex system such as an organ or a living being will respond. We are making progress, slowly but surely. In a small minority of studies, monkeys are the only animals suitable for the study of serious diseases in humans. Pursuant to Dutch law, monkeys can only be used as experimental animals when no alternative method exists. This is why we are doing our utmost to develop such alternative methods.

     

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  • Genetics

    Genetics

    Every species has genetic variability. So do human beings. Such variable genes are called polymorphism. Examples include the genes that determine the colour of a person's hair or eyes. Genes are hereditary, which is why children share certain characteristics with their parents.

    BPRC has a dedicated genetics research department, which focuses on genes for proteins that are part of the immune system. This system plays a major part in infectious diseases, autoimmune diseases and transplant rejections, all of which are fields in which BPRC conducts a great deal of research.

    DNA consists of four chemical bases. The sequence of these bases inside a gene can differ from animal to animal. Thanks to a special technique, we can multiply any gene of our choosing. Using advanced equipment, we will then determine the sequence of the four chemical bases in this gene, which will then be expressed in a sequence of four letters (A, C, G, T). Genes are found in every cell of the body. Each gene contains the code for the production of a protein. These proteins control the biochemical processes. In a way, they are the ones carrying out all the work in our bodies.

    The main focus area of our research

    In our research projects we compare the similarities and differences between the genes of the various primate species (humans, apes and monkeys). Our research mainly focuses on the polymorphic genes of the Major Histocompatibility Complex (MHC) and the killer-cell immunoglobulin-like receptors (KIR). MHC proteins play a crucial role in the recognition of foreign organisms. And when an organ donor and an organ recipient have different MHC, proteins are involved in the transplant rejection. KIR proteins scan cells of the immune system for the presence or absence of MHC proteins. For instance, MHC may be absent from cancer cells or virus-infected cells. If so, KIR proteins will notice the absence and eliminate the cancer cells or virus-infected cells.

    How we select the right animal for the right test

    Proteins coded by polymorphic MHC partially determine whether someone is susceptible or resistant to a particular disease. We can use such MHC-typing to select the right animals for the right tests. This is a great thing, as it enables us to reduce the number of animals we need for experimentation purposes.

    In order to safeguard the quality of the breeding programme for BPRC's colonies and in order to prevent inbreeding, we determine which MHC genes the animals will inherit.

    How we share our expertise

    We only need to sample each animal's blood once in order to isolate its DNA for genetic research purposes. We can also process white blood cells in such a way that these cells will continue to grow in a cell culture flask. In this way we will always have a source from which we will be able to isolate DNA again, even when its donor is no longer available. Everything we learn during these studies is shared with other research institutes through this database, which is curated by BPRC employees. In addition, we make DNA and cell lines available to other research institutes through our Biobank.

     

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  • Ethology

    Ethology

    Ethology is the study of animal behaviour. ‘Behaviour’ includes things such as eating, mating, sleeping and collaboration. Individuals' interactions with their surroundings are determined by their behaviour. This being the case, behaviour is the link between the processes going on between individuals and the rest of the world.

    Animal behaviour, and therefore primate behaviour, is observed on the basis of the four questions formulated by Nico Tinbergen. These encompass the four ways in which biological processes can be studied: from the point of view of fitness value (function), the history of evolution (evolution), the way in which behaviour comes about (mechanism) and the development of the individual's behaviour (ontology). We study the social behaviour and social intelligence of primates from these four angles.

    How monkeys behave

    All diurnal apes and monkeys live in groups featuring a large variety of individuals: young and old, families and outsiders, males and females. They are highly social animals who show off a large variety of social behaviours – behaviours targeted at others. They can be aggressive, but also quite friendly. They will quarrel, but also make up afterwards (reconciliation). In addition, primates recognise members of their own groups and members of other groups, and they maintain different types of social relations, ranging from friendly to neutral or even hostile. It is crucial to the well-being of apes and monkeys that they have the ability to interact with others.

    Social skills and intelligence

    How does monkeys' social behaviour evolve and develop? And how comparable is their behaviour to human behaviour? Our ethological research largely focuses on the evolution and mechanisms of social behaviour. Individuals may have a conflict of interest, in that members of their own species are both potential rivals and potential allies. Whose favour do you curry, and whom do you consider a rival? You need good social skills to recognise potential friends and rivals, which ability forms the basis for monkeys' intelligence, and therefore for human beings' intelligence.

    The focus of our research

    It is believed that this social selection pressure played an important part in the evolution of non-human primate intelligence. It is clear that the way in which monkeys express themselves in a social context depends on the animal's personality, its position in the group, its intelligence and the other monkeys' interests. BPRC's researchers observe how monkeys behave in groups and which factors affect their behaviour. Our monkeys live in pseudo-natural groups which mimic the social dynamics of groups living in the wild. Our observations have contributed to the design of BPRC's current social enclosures for the monkeys, and continue to contribute to this day to improvements to and monitoring of the monkeys' living conditions. It goes without saying that our observations do not cause the animals any discomfort.

     

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Infectious diseases

  • HIV / AIDS

    HIV / AIDS

    AIDS continues to be a major killer on a global scale. More than 33 million people worldwide have been infected with the virus that causes AIDS. Some HIV-positive people seem to have the virus under control, but the majority of patients end up dying of it. Therefore, the further development of powerful vaccines continues to be a top priority.

    The Human Immunodeficiency Virus (HIV) destroys the body's immune system. There are relatively expensive antiviral medications on the market that can somewhat keep this process at bay, but scientists have not yet managed to halt the epidemic. It seems that only vaccines will be able to counteract the spread of HIV. Therefore, a significant part of our research is focused on the mechanism(s) of action of vaccines against HIV.

    How we conduct research on AIDS

    Only humans and chimpanzees can be infected with HIV. However, macaques have proved to be susceptible to an HIV-like virus called SIV (Simian Immunodeficiency Virus), which presents in much the same way as HIV does in humans. Studying this primate model allows us to examine the biological and pathological aspects of HIV. Scientists do not only do so by infecting macaques with SIV, but they have also managed to insert SIV into an HIV shell. This allows them to test vaccines that target the exterior of HIV cells.

    Two focus areas

    A significant portion of our research on AIDS/HIV vaccines is focused on two areas in particular: 1) finding the best possible combinations of HIV proteins to be used in potential vaccines, and 2) optimising the way in which these proteins can be presented to the body's immune system.

    Prevention and control

    BPRC focuses on the development of vaccination strategies involving new combinations of HIV proteins. This means: 1) research on prophylactic vaccines for non-infected people, thus preventing them from being infected, and 2) research on vaccines for HIV-positive people, which will allow their immune system to keep the infection at bay or eliminate it altogether.

    What we are seeking to achieve

    We mainly focus on the mechanism(s) of action of vaccines against HIV, and of vaccines that provide protection against an experimental infection with a particular virus. The question we seek to answer through our studies is as follows: which mechanism(s) of action or activity of the immune system is/are responsible for this protective effect? We call this the ‘correlate of protection’. Every bit of knowledge we gain may constitute a new step towards a more powerful vaccine against AIDS and HIV.

     

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  • Influenza

    Influenza

    Across the world, many people die each year of flu. Generally, the victims are elderly people, young children and people with compromised immune systems. Flu shots do not always prevent people from getting the flu. For this reason, we really need better vaccines.

    Each year, many people receive flu shots targeting the most current forms of flu, caused by the influenza virus. But viruses change ever year, making it hard even to predict which type of virus will hit in a particular winter. Moreover, new sub-types may develop all the time, to which our immune systems are not yet resistant. These new sub-types may result in epidemics or even pandemics (global outbreaks), which may cause many people to fall ill, as well as a high mortality rate.

    What we need for our research

    We really need better vaccines and medications to protect humans from a wider range of flu viruses. We need a suitable animal model, both to identify the factors that cause us to fall ill and to test new vaccines and medications. Apes and monkeys are best suited to this. Out of all animal species, apes and monkeys are most comparable to human beings in terms of immune system and physiology, which is what we need to examine how effective new vaccines are against these human viruses. Rhesus macaques, in particular, have proved to be quite susceptible to infection with the influenza virus. Both the infection itself and the way in which the disease develops in rhesus macaques are very similar to the mechanisms observed in infected humans.

    Our focus area

    A significant part of BPRC's research is focused on the mechanism(s) of action of vaccines against the influenza virus. When a vaccine provides protection against an experimental infection with a particular virus, it is crucial that you understand which mechanism of action or activity of the immune system is responsible for this protective effect. Once you identify the ‘correlate of protection’, you may be able to develop new and possibly better vaccines.

    In addition to using monkeys as animal models, we first assess the safety and efficacy of potential vaccines in cell culture systems. This allows us to select potentially suitable vaccines more quickly, before testing their efficacy in experimental animals.

    Why we need monkeys for our studies

    To this day, clinical trials cannot be held without prior animal testing. After all, cells in a Petri dish can behave completely differently from cells in a living body. In a small minority of studies, monkeys are the only animals suitable for the study of serious diseases in humans. Pursuant to Dutch law, monkeys can only be used as experimental animals when no alternative method exists.

     

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  • Dengue fever

    Dengue fever

    The Dengue virus (DENV) is better known in the Netherlands as the ‘breakbone virus’. This so-called ‘arbovirus’ is transmitted by mosquitoes. Since the 1960s, DENV and related viruses have spread to other parts of the world.

    DENV is transmitted by mosquitoes. Factors contributing to the further spread of this type of virus include global warming (meaning that more places are suitable habitats for mosquitoes), international trade and overseas travelling. The fact that new (invasive) types of mosquitoes have been introduced to Europe and America, such as the notorious tiger mosquito (Aedes albopictus), is mainly due to the latter factor.

    Meet the bad guys

    Specific types of mosquitoes may carry viruses such as DENV, or alternatively, they may carry the Chikungunya virus (CHIKV) and the Zika virus (ZIKV). Recently, the Aedes aegypti mosquito species, which carries DENV, CHIKV and the yellow fever virus (YFV), has entered Madeira and several countries around the Black Sea. Other examples of arboviruses include the Rift Valley Fever virus (RVFV), the West Nile virus (WNV) and the Zika virus (ZIKV). These viruses may be spread by several invasive and endemic mosquito species, generally Culex and Aedes-type species.

    Why more research is necessary

    When humans are infected with these arboviruses, serious and occasionally deadly diseases may ensue, e.g. encephalitis, paralysis and haemorrhagic fever. At present, YFV and Japanese encephalitis virus (JEV) are the only mosquito-transmitted viruses for which a vaccine ready for human use is available. There are no effective vaccines and antiviral medications for infections caused by DENV and other emerging viruses, such as WNV, CHIKV and RVFV.

    What BPRC's researchers are examining

    BPRC's research mainly focuses on emerging mosquito-transmitted arboviruses. We infect macaques and marmosets with mosquito-transmitted viruses, so that our researchers can examine 1) the biology of these viruses, and 2) the pathology caused by these viruses. Moreover, due to their immunological similarity to humans, these monkeys make good animal models for the pre-clinical evaluation of potential vaccines or antiviral medications.

    BPRC-affiliated researchers use the DENV infection model in rhesus macaques to 1) study the efficacy of antiviral compounds, and 2) assess the immunogenicity and efficacy of vaccines. In addition, our researchers use cell cultures for the in vitro characterisation of the vaccine-induced antibody immune responses. Other studies focus on things that happen in cells just after the infection, a stage of the infection that cannot be examined in humans.

    Why we need monkeys for our studies

    To this day, clinical trials cannot be held without prior animal testing. After all, cells in a Petri dish can behave completely differently from cells in a living body. In a small minority of studies, monkeys are the only animals suitable for the study of serious diseases in humans. Pursuant to Dutch law, monkeys can only be used as experimental animals when no alternative method exists.

     

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  • West Nile

    The West Nile virus

    A relatively unknown disease that should not be underestimated in the Western world is caused by the West Nile virus (WNV). Just like Dengue virus, it is an arbovirus, transmitted by insects such as flies, ticks and mosquitoes.

    The virus made it to Europe and America in the 1990s. Until that time, the various genetic variants of the virus were predominantly found in Africa, India and Australia. WNV was first isolated in the West Nile district in Uganda in 1937.

    How WNV travels

    Birds are the main hosts of WNV. Generally, they do not appear to have many symptoms, but their blood may contain enormous quantities of the virus. Blood-sucking mosquitoes can then transmit the virus to incidental hosts, such as humans.

    How we as humans notice a WNV infection

    Eighty percent of humans do not even notice that they have been infected with WNV. The remaining 20 percent suffer flu-like symptoms, also known as ‘West Nile fever’. WNV infection will cause severe symptoms, such as encephalitis and meningitis, in less than 1% of patients. WNV infections can be deadly (&It; 0.1%), particularly in people with compromised immune systems.

    BPRC's research focus areas

    BPRC's research is mainly focused on emerging mosquito-transmitted arboviruses. We can infect macaques and marmosets with mosquito-transmitted viruses, so that our researchers can examine 1) the biology of these viruses, and 2) the pathology caused by these viruses. Moreover, due to their immunological similarity to humans, these monkeys make good animal models for the pre-clinical evaluation of potential vaccines or antiviral medications.

    BPRC-affiliated researchers use WNV infection models in rhesus macaques and marmosets to assess the immunogenicity and efficacy of vaccines. So far, the study results have been promising.

     

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  • Tuberculosis

    Tuberculosis

    Tuberculosis continues to be one of the most serious infectious diseases in the world. It is estimated that one person dies every twenty seconds due to the consequences of infection with Mycobacterium tuberculosis. Moreover, approximately one quarter of the world's population have been infected without realising it, meaning that a new outbreak could happen any time. New therapies must be developed as a matter of urgency.

    An effective vaccine against the consequences of infection at a young age has been on the market for several decades now: BCG (Bacille Calmette-Guérin). However, this vaccine has been found to be insufficiently effective against life-threatening tuberculous pneumonia at a later age. Moreover, this vaccine can cause severe adverse reactions in people with impaired immune systems. In addition, antibiotic-resistant strains of TB are increasingly common. As a result, we are finding it increasingly hard to treat the disease.

    Why we need better medications

    Although antibiotics are available on top of the BCG vaccine, infection with Mycobacterium tuberculosis requires treatment that will take many long months (as opposed to just a few days). Therefore, we urgently need a better vaccine (or vaccine programme) to combat tuberculosis, both with a view to prevention and with a view to curing the disease (therapy).

    It is clear that we need better medications. However, it is proving quite hard to develop effective therapies quickly. What is stopping us is 1) a limited understanding of the mechanisms protecting host humans from TB, and 2) the various immunoevasive strategies of the pathogen, Mycobacterium tuberculosis. Many of these issues can be solved by using an animal model.

    The predictive power and development of new medications

    Macaques may play a vital part in our studies focusing on the prevention and treatment of TB. Macaques are very similar to humans, in terms of their immune system, but particularly in terms of their susceptibility to tuberculosis and the way in which the disease presents, which is similar to the way it presents in humans. The BCG vaccine's protective effect appears to be as variable in monkeys as it is in humans. For this reason, macaques have greater predictive power for humans in this case than any other animal model.

    Both in human beings and in non-human primates, the BCG vaccine suppresses the disease, but does not protect us from being infected with Mycobacterium tuberculosis. In other words, we should probably seek to develop a better vaccine or different type of therapy. Monkeys give us the opportunity to evaluate the efficacy of such new therapies or vaccines in a model that resembles human beings.

    Greater understanding

    Following extensive preliminary studies, BPRC assesses potential vaccines in primate models for safety (are there any adverse reactions?), immunogenicity and protective efficacy. These studies allow us to examine the complex host-pathogen interaction under controlled conditions. Using the results of these studies and our improved understanding of this infectious disease, we seek to contribute to the development of improved therapies.


    Why we need monkeys for our studies

    In some TB studies, monkeys are the most useful animal models. Pursuant to Dutch law, monkeys can only be used as experimental animals when no alternative method exists.

     

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  • Malaria

    Malaria

    Every year, nearly half a million people die of malaria. The majority of the victims are children under the age of 5 in sub-Saharan Africa. There are medications, but these tend to lose their efficacy because the parasite will become resistant. Genuinely effective vaccines are not yet available.

    Every year, nearly half a million people die of the most severe form of malaria, which is particularly prevalent among the poorest people in the world. In addition, there is another form of malaria which tends to be less fatal, but does often cause severe illness. This widespread form of malaria (called vivax-type malaria) annually causes some 14 million people to fall ill.

    What the parasites do

    Malaria is caused by parasites which are transmitted by mosquitoes. Following a mosquito bite, several hundreds of parasites will travel from the blood to the liver, where they will generally mature and reproduce within two weeks. The liver cell will then burst, causing all these new parasites to bring about the sepsis (blood infection) that makes people ill. If that weren't quite bad enough in itself, it was found thirty years ago that there is a type of malaria some of whose parasites remain ‘dormant’ in the liver. In recent years we have learned more about the biology of this ‘dormant’ parasite.

    Complicating factors

    In our mission to eradicate malaria (which is an objective shared by researchers and policymakers alike), we will need new and effective medications as well as vaccines. It is quite hard to research antimalarial vaccines and medications, because malaria parasites have a complex life cycle. What makes it so complex is that the parasites do not only develop in the mosquitoes carrying the malaria, but in the human liver, and then in the human blood. In addition, the parasites are highly able to survive in human hosts. Natural human immune systems tend to be incapable of eradicating the parasites. We will have to come up with vaccines that can do a better job of it.

    How we conduct our research

    Studies examining malaria parasites in rhesus macaques are a good reflection of what happens inside human beings. After all, the malaria parasites hosted by humans and rhesus macaques are closely related. Due to this close kinship, humans can be infected by parasites hosted by monkeys. In addition, monkeys' immune systems and metabolism are a lot like ours, too. Moreover, the unique characteristic of one of the main malaria parasites hosted by humans (the fact that it forms ‘dormant’ parasites in the liver) can be found in certain malaria parasites living in monkeys, as well. This means that monkey models are particularly well suited to pre-clinical trials* examining the safety and efficacy of new medications and vaccines.

    In addition to studies involving animal testing, we also focus on methods designed to reduce the number of animals used in experiments, e.g. by establishing culture systems for the various types of parasites.

    Our focus areas

    A significant part of our research is focused on the creation of new vaccines and medications. In the initial stages, we will mainly use parasites cultivated in test tubes. Using state-of-the-art techniques, we will seek to understand the parasites' weaknesses. We also test the efficacy of new medications against ‘dormant’ liver forms of the parasite in a test tube model we have developed ourselves. Only if an active ingredient proves effective in a test tube will we test its efficacy in a monkey model, using a real malaria infection.

    * BPRC has developed a new vaccine against malaria, called AMA1. This vaccine offers protection against the blood forms of the parasite. Thanks to pre-clinical trials in monkey models, we were then able to trial this vaccine in humans. Trials in Paris and Burkina Faso have shown that the vaccine is safe and provokes an immune response. Further trials involving human subjects will have to demonstrate whether this vaccine can help us provide actual protection against malaria.

    Why we need monkeys for our studies

    To this day, clinical trials cannot be held without prior animal testing. After all, cells in a Petri dish can behave completely differently from cells in a complex immune system. In a small minority of studies, monkeys are the animals most suitable for the study of serious diseases in humans. Pursuant to Dutch law, monkeys can only be used as experimental animals when no alternative method exists.

     

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Chronic and degenerative diseases

  • Multiple Sclerosis (MS)

    Multiple Sclerosis (MS)

    Although we are learning more and more about MS, we are still not certain what causes this disease. Furthermore, we have no idea what mechanisms cause the development of the disease, which makes it hard to develop effective medications.

    What we do know

    MS is an autoimmune disease, which means that the immune system has an adverse reaction to its own organs, resulting in inflammation and damage to tissues. In MS, this adverse reaction targets the myelin sheath that protects the neural pathways in the central nervous system, i.e., in the brain and spinal cord.

    How to improve predictive power

    Trials in mice have proved their importance. However, trials involving experimental mice and rats tell us relatively little about how effective a new MS therapy will be in humans. All too often, new therapies that look promising in animal models do not prove effective at all in human patients. Worse, some of these therapies actually cause patients to experience unexpected adverse reactions.

    Experimental models in monkeys are much more promising in research on the cause and pathogenesis of MS. This is particularly true for experimental models in rhesus macaques and marmosets, because these animals are much more immunologically similar to humans than mice or rats. Therefore, these animal models play a vital role at BPRC in bridging the gap between mice and humans.

    What we focus on in our research

    BPRC's research projects have two equally important components: applied and exploratory research.

    Exploratory research

    Which immunological mechanisms cause MS and determine its clinical course? The purpose of our studies is to find an answer to this question. To do so, we use the variables in monkeys' susceptibility to the EAE (experimental autoimmune encephalomyelitis) model of MS. As with people, these are determined by a combination of hereditary factors and environmental factors*. Nearly all known MS susceptibility genes play are involved in the immune system.

    *The main environmental factors in humans are 1) infection with viruses and/or bacteria, 2) sunshine (vital for the creation of vitamin D) and 3) lifestyle factors, e.g. diet and smoking. Since marmosets and rhesus macaques are so similar to humans, EAE models are very useful in examining which pathomechanisms are affected by the effects of genetic susceptibility and infection.

    If we observe that the physical or functional elimination of a certain cell or molecule has a major effect on the disease, it seems logical to assume that the cell or molecule in question plays a vital part in the disease process.

    Applied research

    The insights we have obtained from our exploratory research allow us to develop disease-specific therapies. We do so in close cooperation with the research & development departments of international pharmaceutical and biotechnological companies in particular.

    Why we need monkeys for our studies

    To this day, clinical trials cannot be held without prior animal testing. After all, cells in a Petri dish can behave completely differently from cells in a living body. In a small minority of studies, monkeys are the only animals suitable for the study of serious diseases in humans. Pursuant to Dutch law, monkeys can only be used as experimental animals when no alternative method exists.

     

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  • Parkinson's disease

    Parkinson's disease

    About one in one hundred people over the age of 55 and about three in one hundred people over the age 0f 70 will suffer from Parkinson's disease. This makes this disease the second most common neurodegenerative disorder after Alzheimer's. In 5% of cases there is a genetic component, but in the great majority of patients, the cause is unknown.

    The medications currently available mainly suppress the symptoms of the disease, e.g. through dopamine replacement therapy. There is no medication that will halt and/or undo the underlying damage. For this reason, there is an urgent need for research on effective medications and therapies.

    What we know

    The disease is caused by the death of special nerve cells (dopamine-producing neurons) in a specific part of the brain that controls motor functions. In addition, misfolded proteins accumulate in the brain. Parkinson's patients generally start showing clinical motor symptoms such as shaking (hyperkinesia) and hypokinetic rigid syndrome at around age 60. Certain ‘premotor’ symptoms can be observed at an early stage, as well, such as REM sleep behaviour disorder, constipation, depression and forms of dementia.

    How BPRC contributes to the fight against Parkinson's disease

    BPRC's research focuses on three particular areas:

    • The development of quantifiable detection methods for premotor and motor symptoms
    • An understanding of the processes that contribute to brain damage and the clinical symptoms of Parkinson's disease
    • The development of therapies designed to 1) halt the damage being caused to the brain, 2) promote the undoing of the damage done, 3) suppress the symptoms of the disease, and 4) prevent the adverse reactions provoked by existing medications.
     
    How we conduct our research

    BPRC has an experimental model for Parkinson's disease that resembles the human brain: the marmoset. Researchers induce the disease by administering a substance called MPTP. Marmosets who have been administered MPTP will develop the symptoms characteristic of Parkinson's disease.

    Why we need monkeys for our studies

    To this day, clinical trials cannot be held without prior animal testing. Parkinson's disease is a complex disorder involving many interactions between various parts of the brain. We are unable to mimic these interactions in individual cells. In addition, cells in a Petri dish can behave completely differently from cells in a living body. In a small minority of studies, monkeys are the only animals suitable for the study of serious diseases in humans. Pursuant to Dutch law, monkeys can only be used as experimental animals when no alternative method exists.

     

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  • Alzheimer's disease

    Alzheimer's disease

    Alzheimer's disease poses a major threat to our ageing society. A new Alzheimer's patient is added every two seconds, which makes Alzheimer's the most common neurodegenerative disease.

    As yet there is no medication that will cure Alzheimer's disease. The medications currently available mainly suppress the short-term memory loss inherent in the disease, e.g. drugs that treat acetylcholine deficiency. However, there is no medication that will halt and/or undo the underlying damage, and we are not even sure what exactly causes the disease. Therefore, research on this disease and effective medications and therapies is desirable.

     

    What we do know

    The disease develops when the connections between nerve cells in the brain die. Basically, the brain shrinks when this happens. The process starts with misfolded protein accumulating between the cells (beta-amyloid), and later inside the cells (Tau). However, we do not know what causes this to happen. There are several factors that accelerate the process, such as inflammation or sleep deprivation. There are also factors that slow down the process, such as exercise. Most of the damage occurs in the cerebral cortex and in an area that plays an important role in memory processes, i.e., the hippocampus. When the connections between the various parts of the brain are lost, memories cannot be retrieved in the regular fashion, and logical connections between events disappear.

    How BPRC contributes to the fight against Alzheimer's disease

    BPRC's research focuses on three particular areas:

    • The development of quantifiable detection methods for memory disorders and methods to measure the connections between various areas of the brain
    • An understanding of the processes that contribute to brain damage and the clinical symptoms of Alzheimer's disease
    • The development of therapies designed to 1) halt the damage being caused to the brain, 2) promote the undoing of the damage done, and 3) suppress the symptoms of the disease.
     
    How we conduct our research

    BPRC has a model for Alzheimer's disease that resembles the human brain: the marmoset. This model targets the formation of beta-amyloid protein accumulations (plaques). Ageing monkeys develop such plaques, just like humans do. This process can be accelerated through stimulation with inflammation factors. Using this model, we can assess which factors play a role in the process, which may give us some clues as to how to develop therapies in future. EEG monitoring allows us to measure brain activity, which helps us determine the extent to which regular processes are interrupted. In addition, brain pathology allows us to measure changes in proteins and infection factors.

    Why we need monkeys for our studies

    Alzheimer's disease is a complex disorder in which interactions between areas of the brain are interrupted, which results in behaviour change and memory loss. We are unable to mimic these interrupted interactions in individual cells. In a small minority of studies, monkeys are the only animals suitable for the study of serious diseases in humans. Pursuant to Dutch law, monkeys can only be used as experimental animals when no alternative method exists.

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Our study results

The results of our studies have been significant. Not only have they helped cure serious diseases, but they have made a proper contribution to science. In addition, our studies on experimental methods that do not require animal testing have presented us with new perspectives that will help us replace, refine and reduce animal testing.

Our study results (pdf)