Methods of treating anti-NMDAR-associated neuropsychiatric disorders
The present disclosure is directed to methods for treating a neuropsychiatric disorder associated with expression of autoantibodies to ionotropic glutamate receptor, NMD A 2A (GiuN2A), expression of anti-double-stranded (ds) DNA antibodies that cross react with one or more subunits of the NMD A receptor, or a mutation in the ionotropic glutamate receptor NMD A type subunit 2A (GRIN2A) gene. The methods involve administering a memantine, or a pharmaceutically acceptable salt thereof, to a subject suffering from a neuropsychiatric disorder associated with expression of GluN2A or a mutation in the GRIN2A gene.
1 . A method of treating neuropsychiatric systemic lupus erythematosus (NPSLE) or systemic lupus erythematosus (SLE) with neurological manifestations in a human subject in need of treatment, the method comprising:
administering to the subject 25 mg/day to 40 mg/day of memantine or a pharmaceutically acceptable salt thereof.
2 . The method of claim 1 , wherein the subject exhibits one or more of the following symptoms: seizures, psychosis, epilepsy, a cerebrovascular event, lesion of cranial nerves, motor disturbances, quantitative alterations of consciousness, cognitive dysfunction, headache, peripheral neuropathy, aseptic meningitis, demyelinating syndrome, movement disorder, myelopathy, acute confusional state, anxiety disorder, mood disorder, acute inflammatory demyelinating, polyradiculoneuropathy, autonomic disorder, myasthenia gravis, cranial neuropathy, plexopathy, polyneuropathy, aphasia, and/or fatigue.
3 . The method of claim 1 , wherein the subject has a mutation in the ionotropic glutamate receptor NMDA type subunit 2A (GRIN2A) gene.
4 . The method of claim 3 , wherein the mutation results in a T141M amino acid substitution in the ionotropic glutamate receptor, NMDA 2A (GluN2A).
5 . The method of claim 1 , wherein the subject expresses autoantibodies to ionotropic glutamate receptor, NMDA 2A (GluN2A); and
wherein the autoantibodies are antibodies to the NR2A subunit(s) DWDYS (residues 283-287) and/or DWEYS of NMDAR.
6 . The method of claim 1 , wherein the pharmaceutically acceptable salt of memantine is memantine hydrochloride.
7 . The method of claim 1 , wherein the subject expresses autoantibodies to ionotropic glutamate receptor, NMDA 2A (GluN2A) and/or anti-ds DNA antibodies that cross react with one or more subunits of the NMDA receptor and has cognitive impairment.
8 . The method of claim 7 , wherein the method further comprises, before the administration of memantine:
obtaining a sample from the subject; and
detecting autoantibodies to GluN2A and/or anti-ds DNA antibodies that cross react with one or more subunits of the NMDA receptor in the sample.
9 . The method of claim 1 , wherein the method comprises administering to the subject 30 mg/day to 40 mg/day of memantine or a pharmaceutically acceptable salt thereof.