This week in therapeutics

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Neurology

Epilepsy

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;
doi:10.1038/ng.2726
Contact: Pierre Szepetowski, Aix-Marseille University, Marseille, France
e-mail:
pierre.szepetowski@inserm.fr


Carvill, G.L. et al. Nat. Genet.; published online Aug. 11, 2013;
doi:10.1038/ng.2727
Contact: Heather C. Mefford, University of Washington, Seattle, Wash.
e-mail:
hmefford@u.washington.edu

Contact: Ingrid E. Scheffer, The University of Melbourne, Melbourne, Victoria, Australia
e-mail:
scheffer@unimelb.edu.au


Lemke, J.R. et al. Nat. Genet.; published online Aug. 11, 2013;
doi:10.1038/ng.2728
Contact: Sarah von Spiczak, Kiel University, Kiel, Germany
e-mail:
s.vonspiczak@pedneuro.uni-kiel.de

Contact: Holger Lerche, University of Tuebingen, Tuebingen, Germany
e-mail:
holger.lerche@uni-tuebingen.de