In order to provide the best possible care to patients with a rare condition, it is essential that global knowledge about the condition is gathered. Nationwide, centers of expertise have been set up to stimulate care for rare disorders and to gather knowledge. For the formal recognition of an expertise center by the Ministry of Health, an important condition is that the expertise center gathers, analyzes and shares knowledge through publications. These can be publications in scientific journals, but also treatment guidelines for health care professionals or information brochures for patients or caregivers. We optimize care and research within ENCORE through standardized follow-up and close collaboration between doctors and researchers. That way, we can ultimately develop better treatments for rare conditions. 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. All research has been approved in advance by an ethics review committee.
Genetic research will be performed on all patients seen in our expertise center to determine the genetic cause and to be able to support and advise the parents. If this genetic research has already been done elsewhere, it will not be done again. This genetic knowledge also helps us to better understand the effect of the genetic change ("mutation") on the severity of symptoms. We can then also investigate which treatment works best for a particular genetic change. In some cases, the genetic change is inconclusive. In these cases, the genetic change will be further investigated in the laboratory (see pre-clinical examination).
Within the GRIN expertise center, detailed knowledge about the course of GRIN Syndrome (which symptoms and complaints are there, and when exactly do they arise) will be collected to learn more about GRIN Syndrome. This is also of great importance to be able to recognize complaints early in the future and to treat them optimally. In addition, this is of great importance for drug research (trials). After all, only if we can demonstrate that a new drug improves the quality of life compared to an untreated patient, will the drug actually be approved and reimbursed.
In addition to permission to record these clinical data, you may be asked to provide a tube of blood for research. This blood is used to generate iPSC (induced Pluripotent Stem Cells) for research. Brain cells can be grown from these iPS cells. See the pre-clinical research page on this website for more information about iPS research.
There are several studies that patients with GRI(N) syndrome can participate in. Below we give a brief explanation of each study. We also explain which patients are eligible for which study. Participation in a study is always voluntary. If you want to participate, you must first sign a consent form. You can withdraw this at any time without reason.
VOLG-study
The first study is also called the VOLG study (Translates to: Early Recognition of Physical and Learning/Behavioral Problems in Children with Inherited Neurocognitive Disorders). The data we collect at the outpatient clinic are valuable for mapping the development and problems associated with GRI disorders. No additional data will be collected from your child specifically for this study. It will also not affect any diagnostics and care your child will receive. For this study, you will receive a consent form by post for your first appointment at the outpatient clinic.
We collect the data during the check-up appointments at the outpatient clinic. This is done at predetermined ages, as stated in the chapter on the GRI(N)-outpatient clinic.
Pediatric brainlab
This research was set up by the Children's Brain Center of the Erasmus MC and TU Delft, of which the Children's Brain Lab is a part. Within this center, various specialists work together to improve the care for children with conditions such as GRI(N). The aim of the research is to better understand the course of brain disorders and to develop tests with which we can measure the course of the disease. And if possible, also to improve treatments for children with a brain disorder. With this research we hope to be able to answer the why in the future to questions about the future, differences between children and treatments.
For this study, you will be asked to fill out some digital questionnaires and come to the Children's Brain Lab. During a visit to the lab, measurements and tests will be done in a playful way. This will take half a day to a maximum of two half days. A total of three rooms will be visited: the thinking room, the engine room, and the movement room. Here we test, among other things, intelligence, the functioning of the brain and senses, and motor skills.
The questionnaires and visits are scheduled at predetermined ages (0-12 months, 30-42 months, 5-8 years, 9-14 years and 15-18 years). An employee of the Children's Brain Lab will contact you about the appointments. They will try, if possible, to coordinate the planning with the KJPP. In this way, both appointments can take place on the same day. This only happens if it is feasible for the KJPP department, the Children's Brain Lab and of course your child.
GRIN Therapeutics Study
GRIN Therapeutics is investigating the drug radiprodil in children with a GRIN-related disorder. The safety of the drug is being examined. In addition, the effectiveness of the drug on epileptic seizures and behavioral problems is being examined.
The study is only for patients with a GRIN-related disorder that has a gain-of-function variant (GoF) in GRIN1, GRIN2A, GRIN2B or GRIN2D. This is because the drug has been specially developed to reduce the overactive signals caused by these GoF variants. There are additional conditions that your child must meet in order to participate in the study. At this time, no new participants are being admitted and GRIN Therapeutics is setting up a subsequent, larger study. This is expected to start in the third/fourth quarter of 2025.
This research is funded by GRIN-Therapeutics. The Erasmus MC is one of the research centers participating. For more information about the study, please visit the website: https://thehoneycombstudy.com/nl-nl/public.
Do you have questions about research at ENCORE? Or do you want to participate? Please contact us via encore@erasmusmc.nl or grin.encore@erasmusmc.nl