A team of researchers from six Dutch knowledge institutions (including coordinator Vrije Universiteit Amsterdam) is introducing new research methods to improve treatment for developmental disorders of the brain. The scientific team will work together with societal partners, clinical associations and companies as the BRAINMODEL consortium and will implement new stem cell-based methods to improve diagnostics and therapy decisions and to develop new therapies. The Netherlands Organisation for Health Research and Development (ZonMw) has allocated a grant of 4 million euros for this work.
For many brain disorders, it is becoming increasingly clear which DNA variation contributes to disease. However, an effective systematic approach for linking this knowledge and the underlying biological mechanisms to treatment options is mostly lacking.
Living nerve cells in a dish
BRAINMODEL’s new approach is based on patient-derived cells with which networks of living nerve cells are produced in a culture dish. These closely resemble the neural networks in our brains. This is known as ‘pluripotent stem cell technology (iPSC)’ and offers new opportunities in terms of understanding human diseases and finding personalized treatments. IPSC-based strategies are particularly promising for developmental brain disorders, because they overcome the problem of not having access to brain tissue to study underlying causes.
The BRAINMODEL consortium aims to integrate these methods with diagnostic techniques and relate them to other technologies such as EEG (with 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.
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 outcome measures, such as EEG biomarkers and patient-relevant 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 Radboudumc expert center for rare genetic disorders 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 drug research, including the design of new drugs. To this end, cellular analyses will be automated and scaled up by culturing human nerve cells on nanochips. This way, a hundred times more drugs can be tested and new drugs can be developed.
The BRAINMODEL consortium was founded by Matthijs Verhage (Vrije Universiteit Amsterdam and Amsterdam UMC, chairperson) and Nael Nadif Kasri (Radboudumc, vice chairperson). Other knowledge institutions represented in BRAINMODEL are Erasmus MC, University of Twente, Radboud University and the Radboudumc expert center for rare genetic disorders. 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). For more information and a list of all the partners in the consortium, please see Consortium.
We bike together to raise money for research towards new treatments for the rare disorder STXBP1 Encephalopathy!
We will raise money for rare disease research on Saturday, June 11, 2022, as European counterpart of The Million Dollar Bike Ride organized by the Orphan Disease Center in the US.
Researchers working on STXBP1 encephalopathy from the VU University and Amsterdam UMC (Netherlands) and University of Antwerp and Antwerp University Hospital (Belgium) will bike towards a halfway point between their labs in Amsterdam and Antwerp. With this combined 170 kilometer bike ride, we hope to raise as much money as possible to aim for a better future for patients suffering from rare disorders. All donations will be transferred to the STXBP1 team of The Million Dollar Bike Ride campaign of the Orphan Disease Center, which supports research towards new treatments for rare disorders.
Please donate here.
If you are interested in riding along with us, or would like to join us at the middle point, please contact us at email@example.com.
STXBP1 Encephalopathy is a severe genetic disease caused by a disease causing variant in the STXBP1 gene. STXBP1-E patients show a developmental delay in their first years, typically resulting in intellectual disability at a later age. Epilepsy is a common symptom (89% of patients) and is difficult to treat. Many patients also suffer from additional symptoms, such as movement disorders (e.g. muscle hypotonia, ataxia) or neuropsychiatric features such as autism spectrum disorder. The severity of the disorder differs between patients, and until now there is no disease-modulating treatment available.
We, researchers at the Vrije Universiteit (VU) Amsterdam and the Amsterdam UMC, the Netherlands, as well as the VIB Center for Molecular Neurology at the University of Antwerp and Antwerp University Hospital, Belgium, work together to better understand STXBP1- Encephalopathy. We aim to improve diagnosis and therapeutic interventions, and study the disease to understand how mutations in STXBP1 lead to STXBP1 encephalopathy. For more information on the disorder and our research, visit our websites stxbp1.cncr.nl and Sarah Weckhysen lab .
The first results of the BRAINmodel consortium have been published as a concept paper in the scientific magazine Genes. This is a flying start for the consortium, which just started a few months ago, and it is great to see the recognition of our work and plans by the scientific community.
In the paper ‘Following Excitation/Inhibition Ratio Homeostasis from Synapse to EEG in Monogenetic Neurodevelopmental Disorders’ we present our strategy to integrate multiple levels of neuroscientific investigations to develop personalized treatment strategies in patients with neurodevelopmental disorders. We focus on excitation/inhibition ratio homeostasis across cellular and in-patient measurements in patients with chromatin- and SNAREopathies.
Please find the full text: https://doi.org/10.3390/genes13020390