“By having brain measurements conducted at home, we hope to discover what triggers migraine attacks, without the use of animal studies.”
'One in three women of reproductive age and one in six men regularly suffer migraine attacks, some even daily. Currently, no drug is available to prevent migraine attacks, which are unpredictable. However, Else Tolner and her colleagues at Leiden University Medical Centre (LUMC) are hoping to change that. They are researching the mechanisms that trigger migraine attacks through LUMC’s Brain@home project, which involves monitoring patients at home. “This means that fewer animal studies are needed in researching these types of brain diseases. In addition, it enables us to do more targeted research, thanks to the data we gather directly from patients.'
Medical biologist Tolner (45) specialises in brain research. Her fascination for this research field developed at an early age. “I suffered from febrile convulsions as a child. The GP in our village thought, erroneously, that my febrile convulsions were a sign that I would develop epilepsy. That’s how I became interested in this important and fascinating disease.”
“I suffered from febrile convulsions as a child. That’s how I became interested in this disease.”
During her internships in Utrecht and San Diego, Tolner specialised in brain research. “I then got the opportunity as a PhD student to work on epilepsy with the late professor Fernando Lopes da Silva at the University of Amsterdam, which I eagerly seized. Prof. Lopes da Silva was an expert in the field of electroencephalography (EEG). The research was done on the basis of measurements in patients and laboratory animals. Later on, I worked as a post-doctoral researcher in Berlin and Helsinki, where I conducted combined animal and human studies. I researched mechanisms and EEG changes that play a role in chronic epilepsy, brain development and febrile convulsions.”
‘Standard’ migraine patient
The aspects relating to the development of EEG and its applications have also proved useful to the Brain@home project Tolner is now involved in. In this project, which will start in January 2021, Tolner and her colleagues will look at patient groups with epilepsy or migraine by means of EEG and behavioural studies, in close collaboration with various experts. The project is led by researchers from LUMC and the Epilepsy Foundation of the Netherlands (SEIN): Professor Arn van den Maagdenberg, Neurologist Roland Thijs and Professor Gisela Terwindt. The project’s research into migraine will focus on ‘standard’ migraine patients.
“In my previous research projects, I learned that it’s important to do measurements in patients. For example, to measure the effects of changes in breathing and acidity (pH) on epileptic seizures. Physicians traditionally measure brain activity in epilepsy patients with EEG, but for migraines, that is far more complex, as headaches are not easy to measure.”
“Physicians traditionally measure brain activity in epilepsy patients with EEG, but for migraines, that is far more complex, as headaches are not easy to measure.”
“With Brain@home, migraine patients can measure their brain activity every day at home in roughly 30 minutes, allowing you to see when any changes occur. By having daily measurements, we hope to gain insight into what happens before the onset of headaches, to enable timely interventions. Our aim is to gather EEG data on at least six days of the week through these measurements.”
“By combining the brain activity measurements with measurements of the patient’s behaviour, we obtain a broad spectrum of data, enabling us to get a better view of what happens in the brain and the rest of the body. In this way, we hope to learn more about the disease mechanism and the functional biomarkers, which not only give insight into what triggers the disease, but also into the likelihood that someone will have an attack. We hope that such data will eventually help us to determine which medicines we can use to treat migraine. That would enable us to greatly reduce patients’ complaints.”
“Where possible, we work without laboratory animals.”
“Where possible, we work without laboratory animals,” Tolner says. “The interests of the patients come first. We want to understand how we can remove their complaints. In addition, we work with
brain-on-chip models in the lab to see how medicines work. We also use computer models and AI where possible. But there are still questions we can only answer through animal studies. In short, every model has its limitations. That is why we use different models alongside each other in the lab and in the clinic.”
Accordingly, Tolner thinks it is still too early to predict whether medical research will ever be completely animal-free. The debate about this is partly about ethics and how society feels about the use of animal studies. I expect that, by looking at research critically, we will increasingly be able to make animal testing more targeted and use fewer laboratory animals. But whether that will eventually lead to a total cessation of animal testing will depend on the usability of human models. Furthermore, having a human brain organoid in a cell-culture dish also raises philosophical and ethical debates. I think it’s unrealistic to aim for entirely animal-free research. If you decide to no longer use laboratory animals, your run into the problem that you cannot do comprehensive testing on a patient. And literally building a living human being in a cell-culture dish is not possible and certainly not desirable.”