At UTOMIC we focus on enabeling translational research in key areas that will benefit both humans and animals. We believe in accelerating innovation through projects that connect One Medicine research and healthcare, and at the same time obviate the use of laboratory animals.
Veterinary researchers from Utrecht University and clinical researchers from various university medical centres have recently been working together on a number of promising One Medicine pilot projects aimed at helping human as well as veterinary patients suffering from a non-communicable disease. Here are a few examples:
In some forms of cancer, radiation (with a linear accelerator) is the only way to effectively combat cancer. Radiation (radiotherapy) is particularly important in cancer forms which cannot be removed or removed operatively.
A standard therapy with a linear accelerator in humans often consists of up to 35 radiation treatments. However, despite the effectiveness of the therapy, radiation treatment remains highly harmful to the patient (animal and human). In veterinary patients the number of treatments has been reduced significantly to 16 times in recent years, showing the same effectiveness with less side effects. On the basis of these findings, the number of radiation treatments in human radiotherapy has now also been reduced.
However, for veterinary patients, the burden of radiation treatment is still heavy, because each time they undergo radiation, they must be brought under anesthesia. That’s why researchers at the Faculty of Veterinary Medicine continue to work with colleagues at UMC Utrecht, on a way to further reduce the number of radiation treatments. Using the new UTOMIC linear accelerator, including advanced software made possible by our partners, our researchers can now aim the radiation more precisely and thus reduce the number of treatments from 16 to 10 per therapy. That way they hope to help animals with cancer even better.
Osteosarcoma is the most common and very aggressive type of bone cancer in children and young adults. Once the tumor is metastasized to the rest of the body, effective treatment becomes increasingly difficult. At present, the survival rate is only 13-30% 5 years after the diagnosis. Osteosarcoma also occurs in veterinary patients, especially dogs. In some dog breeds, prevalence can be up to 27 times higher than in humans.
To develop more effective treatment strategies, clinicians must first understand the nature and behaviour of the tumor, ideally using a Magnetic Resonance Imaging (MRI) scan, which makes it possible to assess the tumor in relation to the surrounding tissues. However, in human patients with osteosarcoma, chemotherapy treatments are started immediately after the diagnosis, even before surgery takes place, making (histopathological) MRI studies more difficult. In dogs, on the other hand, diagnostic imaging is always performed before any kind of treatment takes place. Innovative MRI methods for investigating the tumor in detail can be developed much more easily.
The scientific literature describes sufficient similarities between the etiology and prevalence of osteosarcoma in humans and animals to establish that there is a lot to gain from joining forces for both human doctors and veterinarians. In cooperation with the UMC Utrecht and the Princess Máxima Centrum, the Faculty of Veterinary Medicine has set up a study with 10 dogs with the diagnosis of osteosarcoma.
UTOMIC researchers hope to gain more insight into the tumor and the relationship with the surrounding structures through the use of MRI. Subsequently, they hope to expand their research and explore the immunological environment of osteosarcoma. In addition, they want to investigate the effectiveness of pharmacokinetics and pharmacodynamics of new immune therapies, for both humans and dogs.
Hip dysplasia is a common orthopedic condition in both humans and dogs and is characterized by a hip socket that doesn’t fully cover the ball portion of the upper part of the femur. Patients with hip dysplasia often develop osteoarthritis from the hip joint, resulting in a lot of pain, movement limitation and, as a result, a decrease in the quality of life.
Joint research by UMC Utrecht and the Faculty of Veterinary Medicine aims to demonstrate that a number of musculoskeletal diseases, such as hip dysplasia, can be successfully treated with personalized 3D-printed implants. Following on testing on cadavers, the study now aims to treat 25 dog patients with hip dysplasia at the Utrecht University Veterinary Hospital. Successful results will allow personalized 3D printing to be integrated into both veterinary and human medicine.
To produce an exact 3D model, the patient’s hip joint is mapped using computed tomography (CT), producing a 3D image of the skeleton and the deformity. The 3D image is then sent to a highly specialized software program, where the deviations in silico are corrected to develop a model of a personalized 3D implant. A first set of implants is printed from plastic, allowing the surgeon to simulate the operation and ensure that the desired fit is achieved. The final 3D implant is printed from titanium. Once sterilized, the implant can be applied to the patient.
The results of the treatments have so far exceeded all expectations. In a next phase, studies will focus on integrating the technique into human medicine.
Cushing syndrome is a serious hormonal disease in which a tumor in the pituitary gland causes excessive hormone production. The disease occurs in humans as well as dogs. Without treatment, Cushing syndrome terminates fatally. Cushing syndrome is very common in dogs and affects about 1 in 400 dogs. Currently, Mitotaan is the best medicine to treat Cushing syndrome. However, Mitotaan only suppresses the clinical symptoms and has no effect on the tumor itself, besides the fact that it causes serious side effects. The development of alternative medication that prevents the tumor from growing is therefore necessary in order to guarantee effective treatment of human and veterinary patients.
In close collaboration with the Hans Clevers group of the Hubrecht Institute, researchers at the Faculty of Veterinary Medicine have developed a method in which pituitary tumors are grown as growing 3D structures in the laboratory. These pituitary tumor ‘organoids’ or ‘tumoroids’ are actually avatars of the original tumor and can be used to test different medications for their ability to inhibit both hormone production and tumor growth before they are used to treat patients.
Every year around 4 million people are diagnosed with a malignant brain tumor. The average life expectancy is less than a year and the current treatment methods, such as surgery and radiotherapy, rarely lead to healing and are often accompanied by serious side effects.
In dog patients, brain tumors are regularly diagnosed, with similar prevalence, prognoses and treatment options as in human patients. Moreover, there are many similarities between the structure of the brain and the properties of tumors in humans and dogs.
In a joint research project, the Faculty of Veterinary Medicine and the Radboud University Medical Center in Nijmegen have developed a minimally invasive treatment method to treat brain tumors. With the help of MRI and CT, steerable needles inject radioactive holmium balls (‘microspheres’) into the tumor. The radiation levels in surrounding structures are then monitored using a SPECT camera.
With this minimally invasive treatment approach, a higher dose of radiation can be applied than conventional radiotherapy, without damaging the surrounding or healthy tissue, minimizing potential side effects.
A phaeochromocytoma is an adrenaline-producing tumor that develops in an adrenal gland. In humans, this is a very rare condition, which means that current treatment methods are very limited. However, in dogs phaeochromocytoma occur much more often. Over the years, dr. Sara Galac and her team of veterinary researchers from the Faculty of Veterinary Medicine have built a tissue bank with phaeochromocytoma tumor tissue from dog patients.
Surgical removal of the tumor is currently the best treatment option, but in half of the cases the risk is too high because the tumor has been ingrown in surrounding tissue. Researchers therefore grow mini-tumors from surgically removed tumor tissue of dogs, so that they can test new drugs for them, without using laboratory animals. In the future, a medicine for phaeochromocytoma will not only helps dogs with an inoperable tumor, but also humans with the same disease.
Organoids, human-based or animal-based, have shown great potential as viable models to assess the safety of new and existing substances. However, throughput, standardization and regulatory acceptance remain barriers. This is true for safety testing of substances on healthy specimen organoids, but even more so for disease model organoids (e.g. tumoroids). Moreover, disease model organoids usually require laboratory animals as source. However, the high number and variety of spontaneously occurring veterinary diseases equivalent to common human diseases allow the use of tissues of treated veterinary patients as a valid alternative source for material for organoid generation.
This research line will bring together the value chain, i.e., veterinarians, medics, contract research industry, regulatory bodies, societal organizations and animal owners. The overall aim of our project is to overcome critical hurdles towards regulatory acceptance of organoids as recognized alternative for safety testing. We aim to prove the smart strategy of using tissues harvested during clinical treatment of veterinary patients as a laboratory animal-free source for organoids, which can be used to advance precision medicine as well as to gain additional scientific insights at the population level.
All UTOMIC research proposals are conducted after consultation with the Animal Welfare Body Utrecht to ensure optimal animal welfare and scientific quality.