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 testing will be performed on all NF1 patients seen in our center of expertise to determine the genetic cause and to be able to support and advise the parents. If genetic testing has already been done elsewhere, it will not be repeated. 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 mutation. In rare cases, the genetic analysis is inconclusive. In these cases, the genetic change will be further investigated in the laboratory. ENCORE contributed to the improvement of NF1 diagnostics (van Minkelen, Clinical Genetics, 2013).
Within ENCORE we also looked at the effect of the type NF1 mutation on cognitive functions (IQ). We found that all different NF1 mutations produce similar effects, with the exception of the so-called chromosomal micro-deletion. NF1 patients with this mutation are more affected (Ottenhoff, Genetics in Medicine, 2020).
Detailed knowledge about the course of Neurofibromatosis type 1 (which symptoms and complaints are there, and when exactly do they arise) is of great importance in order to be able to recognize complaints early and treat them optimally in the future. 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. ENCORE has done a lot of research in this area, particularly with regard to cognitive functions, and the impact that this has on daily functioning. ENCORE has also conducted extensive research into the mechanisms underlying the cognitive problems in both patients and mouse models of NF1 (see "Our publications" and the preclinical research pages on this site).
ENCORE has conducted a number of clinical trials to investigate if the cognitive problems in NF1 can be ameliorated. We found no indication that statins improved cognitive function. It is currently being investigated whether Lamotrigine can provide an improvement.
The TRAIN study
In addition to these cognitive trials, clinical trials are currently underway with a "MEK inhibitor" that focus on the treatment of the plexiform neurofibromas that occur in NF1. Plexiform neurofibromas can be very damaging cosmetically, but can also lead to neurological deficit, bone growth, blindness, severe pain and aggressive cancer. They are difficult to operate because they have too good blood flow. That is why medicines are badly needed. Recent research shows that children with NF1 and a non-operable plexiform neurofibroma benefited from medicinal treatment. As a result of this study, Erasmus MC will conduct a study with trametinib in adult NF1 patients with plexiform neurofibromas that cause complaints. Click here for English information on trialregister.nl about this study (including inclusion and exclusion criteria).
Neurophysiological outcome measures
For conducting cognitive trials, it is very important to be able to determine quickly and objectively in a small group of patients whether the drug may work or not. That is why we are now focusing on developing techniques to determine these "outcome measures". We do this for instance by using transcranial magnetic stimulation (TMS).
In addition, we use EEG measurements to measure the plasticity of the visual cortex by measuring "visual evoked potentials".
The ENCORE-NF1 expertise center participates in the consortium EU-pearl,, a collaboration between 8 hospitals, a number of pharmaceutical partners, and EFPIA, which aims to set up a framework for "multi-centre multinational platform trials" for a number of syndromes. ErasmusMC-NF1 is working group leader for "WP7 Neurofibromatosis". The overall goals are to establish a clinical research network for trials in NF in Europe, to develop platform trials for drug treatment of complications for NF, and to set up a long-term study of the history of NF manifestations. Click here for more information about the EU-pearl consortium.
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