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NMDAR; NMDA receptor NR2A subtype (GRIN2A; NR2A)

Human genetic and cell culture studies suggest modulating NMDARs could be useful for treating certain forms of epilepsy. Exome sequencing of patients with epilepsy by three independent teams found de novo and inherited mutations in GRIN2A in up to 20% of patients who have idiopathic focal epilepsy, acquired epileptic aphasia, continuous spike and waves during slow-wave sleep syndrome, benign epilepsy with centrotemporal spikes and other variants of epilepsy-aphasia syndromes. In cell culture, several disease-associated GRIN2A mutations caused higher NMDAR ion channel activity than wild-type GRIN2A. Next steps include screening for compounds that normalize the function of GRIN2A with disease-associated mutations.
Mnemosyne Pharmaceuticals Inc. has GRIN2A-selective NMDAR modulators in preclinical development for schizophrenia, depression and autism.
Insero Health Inc. has the NMDAR modulator huperzine A
(INS001) in Phase I testing to treat drug-resistant epilepsy.
At least 20 companies have nonselective NMDAR modulators in development or on the market for various neurological indications.

SciBX 6(35); doi:10.1038/scibx.2013.968
Published online Sept. 12, 2013

Findings from all three studies unpatented; licensing status not applicable

Lesca, G. et al. Nat. Genet.; published online Aug. 11, 2013;
Contact: Pierre Szepetowski, Aix-Marseille University, Marseille, France

Carvill, G.L. et al. Nat. Genet.; published online Aug. 11, 2013;
Contact: Heather C. Mefford, University of Washington, Seattle, Wash.

Contact: Ingrid E. Scheffer, The University of Melbourne, Melbourne, Victoria, Australia

Lemke, J.R. et al. Nat. Genet.; published online Aug. 11, 2013;
Contact: Sarah von Spiczak, Kiel University, Kiel, Germany

Contact: Holger Lerche, University of Tuebingen, Tuebingen, Germany