BRAINMODEL: precision medicine for brain disorders

A team of researchers is going to look for new and better ways to heal developmental disorders in the brain. Six different knowledge institutions are to collaborate with civil societies, professional associations and companies on new stem cell-based methods in a project entitled ‘BRAINMODEL’.

The Netherlands Organisation for Health Research and Development (ZonMw) has allocated a grant of 4 million euros for this work. Vrije Universiteit Amsterdam is the coordinator of BRAINMODEL. The DNA abnormalities responsible for many brain disorders are becoming increasingly clear but there is still no effective systematic approach for linking this knowledge and the underlying biological mechanisms to the treatment options.

Optimal treatment

The BRAINMODEL consortium is founded by Matthijs Verhage (Vrije Universiteit Amsterdam and Amsterdam UMC) and Nael Nadif Kasri (Radboudumc/Donders Institute). It aims to integrate these methods with diagnostic techniques and relate them to other technologies such as EEG (in which brain activity is measured electronically) to find the best possible treatment for individual patients.

BRAINMODEL thus hopes to help optimize therapy choice and make the treatment of brain disorders more successful. At the same time, the researchers will address the ethical and social questions associated with using these technologies together with patients, patient organizations, clinicians, representatives from industry and other societal partners in the consortium.

Floris Rutjes, Professor of Organic and Synthetic Chemistry at Radboud University is one of the researchers at BRAINMODEL: ‘This project will result in new models, which can be used to study if existing medicines are suitable for treating brain disorders. With these models, we can also observe the effect of new compounds, with the aim to eventually develop new medicines. Within the Institute for Molecules and Materials, we will make new small molecules and test these in the BRAINMODEL. This way, we lay the foundation for possible new treatments.

Living nerve cells in a culture dish

The new methods on which BRAINMODEL will work are based on cells harnessed from the patients themselves and used to produce networks of living nerve cells in culture dish. These closely resemble the neural networks in our brains. This is known as ‘pluripotent stem cell technology (iPSC)’ and it offers new opportunities in terms of understanding human diseases and finding personalized treatments. IPSC-based strategies are particularly promising for brain disorders because they work around the problem of researchers not being able to access the brain tissue of living patients to study the underlying causes of diseases.

Linking analyses to measures of outcome

BRAINMODEL’s main objective is to use iPSC-based analyses to detect abnormal cellular functions in material from patients with brain disorders and to link these to clinical measures of outcome, such as EEG biomarkers and symptom scales. The latter work will be carried out in collaboration with two clinical centres: the N=You Kenniscentrum (N=You Knowledge Centre) in Amsterdam and the Vincent van Gogh Institute for Psychiatry in Nijmegen.

The researchers will subsequently test whether abnormal cellular properties, which cause an imbalance between the positive and negative signals that nerve cells send to one another, can be remedied with existing medication in the IPSC-based analyses. If this is the case, the physicians at the associated clinics can use this medication to treat the patients in question. If no existing medication can be found to remedy the abnormal properties, BRAINMODEL will use specially-developed nanochip technology to carry out iPSC-based analyses on a larger scale. This method will enable large-scale medicine research, including the design of new medications. To this end, cellular analyses will be automated and scaled up by culturing human nerve cells on nanochips. This will mean that a hundred times more medicines can be tested and new medicines developed.

PSIDER

The BRAINMODEL consortium has been set up by Matthijs Verhage (Vrije Universiteit Amsterdam and Amsterdam UMC, chairperson) and Nael Nadif Kasri (Donders Institute, vice chairperson). Other knowledge institutions represented in BRAINMODEL are Erasmus MC, University of Twente, Radboud University and the Vincent van Gogh Center for Neuropsychiatry. The consortium has received a grant of four million euros from ZonMw within the framework of the grant call ‘Multidisciplinary Consortia Programme Pluripotent Stem cells for Inherited Diseases and Embryonic Research’ (PSIDER).

Researchers involved in BRAINMODEL, from left to right: Dr Dirk Schubert, Prof. Floris Rutjes, Dr Klaus Linkenkaer Hansen, Dr Nael Nadif Kasri, Dr Niels Cornelisse, Gianina Cristian, Dr Eline Bunnik, Renee Lustenhouwer, Lisa Geertjens, Prof. Matthijs Verhage, Lara Janssen, Dr Ruud Toonen, Miriam Öttl, Dr Claudia Persoon, Torben van Voorst, Prof. Hilgo Bruining, Hanna Lammertse, Annemiek van Berkel, Dr Jennifer Ramautar, Maaike van Boven, Prof. Tjitske Kleefstra