Kleefstrasyndrome.org recently contacted Dr Kleefstra and the team at RadboudUMC, Nijmegen for an update on current Kleefstra Syndrome research. We had received a number of questions in relation to the publication of their most recent paper ‘Neuronal network dysfunction in a human model for Kleefstra syndrome mediated by enhanced NMDAR signaling’ and what it actually means in terms of Kleefstra patients and the possibility of treatment.

We are pleased to offer this short explanation from Nael Nadif Kasri – Associate Professor at RadboudUMC. Of particular interest to many families will be the studies on regression and the use of Olanzapine.  The importance of studies that explore options to help KS symptoms now is critical and we thank the team for their continued efforts and dedication.

Nael Nadif Kasr

“Recently the Nijmegen research group has posted a new study regarding Kleefstra syndrome (KS). Because parents contacted us with several questions I would like to explain in short our findings and what it means for the patients and the family.

In this study we used skin cells from KS patients to generate stem cells. These stem cells have the unique ability to generate any cell type in your body. We used these stem cells to generate ‘neurons’, the main cells residing in our brain. Doing so we studied the difference between neurons from KS patients and non-affected people. We grew these neurons on “smart dishes” allowing us to ‘listen’ when, with who and how often these neurons talk to each other. We found that neurons from KS patient were talking to each other in a different way. Further investigation showed that some proteins that are important for the communication between neurons were different in KS neurons, including an important protein, the NMDA receptor. Subsequently we used this information to restore normal neuron communication. Although we are very excited about the current findings we absolutely want to emphasize that currently this study only has been performed on ‘neurons in a dish’ and therefore is only a first, but important step into KS research. It still has to be defined to what extent this ‘dish phenotype’ is relevant to any of the brain phenotypes (features) in the KS patients. We are using this dish system already in our study on the regression and use of olanzapine in KS patients, currently conducted by clinical team of Dr. Kleefstra. The Nijmegen team, with support of K.I.D.S IQ, will conduct further studies in a whole organism (mice) to test the safety and efficacy of our new strategy.“

Nael Nadif Kasri, April 2019.

Page updated: 19-01-2020