Grant for personalized medication for rare brain disorders Patients are the starting and ending point of this study

Researchers at Radboud university medical center have received a grant of over 500,000 euros from the Dutch Brain Foundation. With this, they will be investigating the possibility of personalized medication for patients with a variant in the CACNA1A gene. Variants in this gene can lead to the movement disorder ataxia, but also to other brain disorders, such as epilepsy and migraines.

A mutation in the CACNA1A gene can lead to ataxia, a movement disorder associated with coordination and balance problems. However, we now know that variants in this specific gene can also lead to epilepsy, migraine and intellectual disabilities. 'These different clinical manifestations can only partly be traced back to the exact mutation in the gene. We therefore think that there is no 'one size fits all' treatment for this disease,' says neurologist Bart van de Warrenburg.

Together with other colleagues from Radboud university medical center, he receives a grant of over 500,000 euros from the Dutch Brain Foundation for research into this specific gene. As a project leader, he will follow patients with different manifestations and different mutations of CACNA1A for a longer period of time. He wants to determine the exact course of the disease per patient and find out what the personalized outcome measures are for the clinical trial later in the process.

Stem cells are extracted from the blood of patients that can be processed into nerve cells. Neurobiologist and co-project leader Nael Nadif Kasri explains: 'We will measure the electrical communication of these nerve cells and map out the disturbed biological processes. In this way, patient-specific mechanisms are revealed.'

Subsequently, the team of bioinformatician Peter Bram 't Hoen will query databases containing existing drugs for similarities between mechanisms of action and the processes found in the nerve cells of the patients. The drugs with the best match are then tested for effects on the cultured nerve cells, again for each individual patient. Finally, in a so-called 'single-case experiment', the drug with the best effect is actually given to the patient to study its clinical effect.

In this way, the individual patient with a mutation in the CACNA1A gene is the starting and ending point of this project. Van de Warrenburg: 'Finding existing drugs that we can use for other diseases, so-called 'drug repurposing', is a promising way of developing therapies for rare diseases. This is because there is a shorter development time, and the costs are lower.' According to him, this research can be used as a blueprint for other rare diseases.