Intrathecal magnesium delivery for Mg++-insensitive NMDA receptor activity due to GRIN1 mutation

Figures

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  Fig. 1. (A) In vitro effect on NMDA receptor activity by variant. *Fold effect calculated only when the 95% confidence intervals (CIs) of experimental datasets did not overlap. Positive values indicate a gain of function effect on NMDA receptor activity for the parameter measured. NE = no effect. A % remaining current measured at pH 6.8 compared to pH 7.6 at maximal L-glutamate and glycine activation; B % residual current in maximum zinc. Results from n = 10–12 oocytes each. (B) A 7 fold reduction in the inhibition sensitivity to endogenous inhibitor Mg++ (based on IC50 potency) was evident. (C) Dose response (spike density, measured as discrete events > 0.0 mV) to escalating doses of intrathecal MgSO4 given each hour. Pre-treatment baseline/washout is depicted as gray bar, treatment epochs in white. (D) Dose response assessing EEG amplitude pre- and post-treatment; pre-treatment baseline/washout is depicted as gray bar, treatment epochs in white. (E) EEG complexity plotted vs. MgSO4 dose; pre-treatment baseline/washout is depicted as gray bar, treatment epochs in white. Error bars indicate standard error