First SNAREopathy treatment started in new N=YOU Center

March 7, 2021
CNCR

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a young patient who carries a SYT1 mutation is the first to receive a mechanism-based treatment with the prescription of bumetanide, aiming to reverse excitation/inhibition disturbance

The new N=YOU CENTER headed by Hilgo Bruining and Matthijs Verhage (FGA) uses new precision medicine approaches to treat children with neurodevelopmental disorders (NDDs). The center integrates clinical manifestations with genetic information, EEG-biomarker data and functional data from human stem cell-based models obtained from the patients themselves (‘patient-own’ neuronal in vitro models). Personalized treatment decisions are made on the basis of this integrated, multimodal information.

Translational research at CNCR aims to elucidate disease mechanisms for a prominent class of monogenetic NDDs, the SNAREopathies, and to establish in vitro models, based on the patient’s own IPSC-derived neurons, to screen compounds, especially off-label drugs, and suggest the most suitable to N=You clinicians for treatment. SNAREopathies are caused by mutations in eight genes that together perform a single molecular function as a highly integrated molecular machine: the secretion of chemical signals in the synapses of the brain. CNCR scientists Maaike van Boven and Niels Cornelisse specialize in mutations in one SNAREopathy gene SYT1. In parallel to the treatment, Maaike and Niels are studying neurons from the first patient in vitro to better understand how the specific mutation in this individual leads to aberrant cellular functions. CNCR studies four other SNAREopathy genes, using patient-own neurons to identify common and unique features among mutations in the different components of this highly integrated molecular machine.