BRAINCHAIN’s multidisciplinary team of researchers, clinicians and legislative experts forms an on-campus Centre of Expertise that generates and integrates knowledge to improve healthcare for patients with genetic neurodevelopmental disorders.
Focus on neurodevelopmental disorders
Neurodevelopmental disorders (NDDs) encompass disorders caused by abnormal brain development. They form a vastly varied group of disorders with a large societal and economic impact. NDDs typically manifest themselves early in development and are associated with a wide range of symptoms that lead to (severe) deficiencies in social, intellectual and occupational functioning.
BRAINCHAIN focuses on rare genetic NDDs affecting around 1:250 live-born children. Also referred to as rare genetic syndromes and Mendelian NDDs, rare genetic NDDs are caused by disruptions in specific, individual genes. With increasing genetic diagnostic possibilities available, a rapidly growing number of Mendelian NDDs are being characterised. However, the current definitions of Mendelian NDDs primarily focus on physical characteristics, while the cognitive and psychiatric symptoms are often present and can burden patients and their caregivers considerably.
There is an urgent need to gain more knowledge about Mendelian NDDs described so far (such as Witteveen-Kolk syndrome, Kleefstra syndrome and KBG syndrome), as well as disorders caused by disruptions in newly identified genes. A greater understanding of the genetic, neurobiological and cognitive backgrounds of these syndromes can lead to significantly better care for patients with Mendelian NDDs and enhance their quality of life.
From molecule to brain and from person to society
That is what BRAINCHAIN stands for. We believe that a multidisciplinary, integrative approach is the best way to improve NDD patients’ well-being and promote participation in society in the long run. In BRAINCHAIN, we brought together top researchers and clinicians on campus in the fields of genetics, brain development, psychology and psychiatry to collaboratively work towards a more direct knowledge chain for the development of treatments for patients with Mendelian NDDs. Assisted by a team of legislative experts, BRAINCHAIN also works on the further development of ethical policies and public health regulations to ensure optimal care for our patients.
BRAINCHAIN forms a Centre of Expertise in which we can integrate newly gained knowledge into the existing knowledge of Mendelian NDDs across all relevant fields. We believe that only together can we tackle the challenges inherent to the treatment of and care for patients with these complex NDDs.
To reach our ultimate goal of developing personalised treatments for NDD patients, we need to improve our understanding of the biological mechanisms underpinning NDDs and the clinical consequences for our patients, as well as further develop policies and regulations that impact patient care. Our research approach, therefore, consists of three branches.
I. Biological Framework
Our research teams focus on the molecular and cellular mechanisms that drive NDDs. We seek to better understand the effects of disturbed gene function on brain development using a combination of in vivo and in vitro research methods (e.g. in utero electroporation, conditional knock-outs and brain organoids). Additionally, we aim to unravel the underlying molecular mechanisms of genes that are known to cause specific syndromes when disturbed (e.g. SIN3A [Witteveen-Kolk syndrome], EHMT1 [Kleefstra syndrome] and ANKRD11 [KBG syndrome]).
II. Diagnostics, Profiling and Personalisation
Our clinical research teams aim to better define Mendelian NDDs on the physical, cognitive and behavioural level. Studies that further characterise the genetic background and physical symptoms observed in our patients are ongoing. In parallel, profiling studies focus on the psychiatric, cognitive and behavioural symptoms of NDD patients, leading to more tailored advice on patient well-being and societal participation. Our clinicians are at the forefront of personalising treatment strategies for NDD patients based on the biological framework and cognitive assessments.
III. Ethics, Regulation and Legislation
BRAINCHAIN aims to reevaluate and revise public health regulations and legislation to develop the societal participation of NDD patients further and ensure optimal care. Research focuses on the biological, psychological, and ethical aspects involved in NDD care and the impact on family and health laws and regulations on a national and European level.
Research on the ethics, regulations and legislation related to NDD patient care is led by members of the Centre for Notarial Law of the Faculty of Law in cooperation with Prof. Jos Egger, Prof. Tjitske Kleefstra, and Prof. Wouter Staal.
- Witteveen JS, Loopstok SR, Ballesteros LL, Boonstra A, van Bakel NHM, van Boekel WHP, Martens GJM, Visser JE, Kolk SM. HGprt deficiency disrupts dopaminergic circuit development in a genetic mouse model of Lesch-Nyhan disease. Cell Mol Life Sci. 2022 Jun 4;79(6):341. doi: 10.1007/s00018-022-04326-x. PMID: 35660973; PMCID: PMC9167210.
- Kolk SM, Rakic P. Development of prefrontal cortex. Neuropsychopharmacology. 2022 Jan;47(1):41-57. doi: 10.1038/s41386-021-01137-9. Epub 2021 Oct 13. PMID: 34645980; PMCID: PMC8511863.
BRAINCHAIN is a fully on-campus initiative, allowing us to collaborate more efficiently and strategically. Our research teams are part of four faculties of Radboud University, the Faculties of Science, Medical Sciences, Social Sciences and Law. These teams work in close collaboration with (clinical) geneticists based in Radboudumc and Max Planck Institute for Psycholinguistics and experts from Vincent van Gogh Centre of Psychiatry and Karakter Academic Medical Centre for Child and Adolescent Psychiatry. Furthermore, BRAINCHAIN’s clinical research teams are strengthened by paediatricians and experts on intellectual disability and language development.
Would you like to reach out to us and learn more about BRAINCHAIN and our research? For any enquiries, please get in touch with Dr Sharon Kolk.