Preclinical research

We are an academic hospital. This means that we consider it important to conduct scientific research into the (rare) disorders that are part of the ENCORE expertise. In this way we increase the knowledge of the underlying cause, diagnosis and treatment of the disorders, and we hope to be able to offer better treatments in the future. Conducting research is also a requirement for the formal recognition of an expertise center by the Ministry of health. You may therefore be asked to participate in research. Participation in research is always on a voluntary basis. The data obtained is stored and analyzed in an anonymous form. The research has been approved in advance by an ethics review committee.

The research within ENCORE can be divided into three main areas:

  • Pre-clinical (basic) research. This (laboratory) research focuses mainly on mouse models and stem cells and is intended to gain more insight into the mechanism underlying the disorders. These new insights should lead to the development of new medicines that improve the quality of life of patients.
  • Clinical (patient-related) research. This research attempts to learn more about the condition by conducting research with patients. Examples of clinical research are the collection of clinical data to gain a good insight into the course of a condition. Comparing the most efficient epilepsy or sleep medication or identifying the best communication technique are also examples of clinical research.
  • Translational research. ENCORE wants to bridge the gap between basic laboratory research and the clinic. To this end, a lot of translational research is being conducted within ENCORE. This can be laboratory research, such as, for example, research into the treatment of epilepsy in a mouse model of a disorder. Translational research can also be patient-related research, such as a clinical trial in which the new drugs developed in the laboratory are tested in patients.

Conducting research is bound by strict (ethical) rules and is assessed by an ethics committee. This applies to both laboratory animal and patient-related research. For "patient-related research", written permission from the parents / guardian is always required. So only if you are willing to participate in research, the patient data will be used (anonymously) for research.

We focus on genetic disorders that cause a disruption in normal (brain) development and therefore lead to intellectual disability, epilepsy and / or behavioral problems (e.g. autism). Clinical care is combined with basic and translational research into the causes and treatment. Because there are hundreds of different genes involved in brain development, we have defined two areas of interest:

  1. Genes that not only affect brain development but are also associated with an increased risk of tumors (in the brain or elsewhere in the body). These are in particular genes that are part of the signaling pathway within the cell. Via this signal pathway, the (brain) cell translates the stimuli it receives into a signal that is sent to the nucleus where the DNA is stored. Activation of this signaling pathway leads to the transcription of DNA and to the production of new proteins that can have very diverse functions in the (brain) cell. Mutations in these genes therefore not only affect the development of the brain, but are usually also associated with an increased risk of tumors elsewhere in the body. This includes genes in the RAS-PI3K-MTOR signaling pathway as well as genes involved in the repair of the DNA:
  • Brain Overgrowth Syndromes
  • Cortical malformation syndromes (MCD)
  • Cardio-Facio-Cutaneous (CFC) Syndrome and Costello Syndrome (CS)
  • DNA repair disorders
  • Neurofibromatosis type 1 (NF1)
  • Sturge-Weber
  • Tuberous Sclerosis Complex (TSC)
  1. Genes that have a direct effect on signaling between brain cells. Brain cells communicate with each other through contact points (synapses). These contact points between brain cells are constantly being adjusted and can decrease or increase in strength ("synaptic plasticity"). This is essential for learning and memory. Impaired synaptic plasticity usually also affects brain development. This causes intellectual disability, epilepsy and / or behavioral disorders (such as autism). We focus in particular on the following disorders:
  • Angelman syndrome (AS)
  • CAMK2 syndrome
  • Dup15q syndrome
  • Fragile X Syndrome (FXS)
  • SYNGAP1 syndrome
  • Glutamate receptor syndromes (GRIN, GRIA)
  • (Ultra) rare genetic disorders that lead to developmental disorders and autism ("Unique clinic")

You can read more about the syndromes and the research on the syndrome specific pages on this site.

You can find additional information about the Elgersma laboratory here

Additional information about the techniques used to determine whether a very rare mutation is pathogenic can be found here