Immunome Research
Open Access
ISSN: 1745-7580
+44-77-2385-9429
ISSN: 1745-7580
+44-77-2385-9429
Uriel Heresco-Levy
Hebrew University, Israel
Posters & Accepted Abstracts: J Immunome Res
Since anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis was first described a decade ago, the family of disorders associated with antibodies (AB) against neuronal surface antigens is one of the most rapidly expanding categories of neurologic disease. We hypothesized that: 1) anti-NMDAR-ABs seropositive patients can be identified among chronic treatment-resistant schizophrenia patients having atypical disease characteristics; and 2) treatment with D-serine (DSR), which acts in vivo as NMDAR co-agonist at the NR1 receptor subunit will be beneficial for the patients. Out of 17 DSM-IV-diagnosed schizophrenia patients, a 67 yr old female patient hospitalized since age 27 was seropositive for both IgG and IgM anti-NR1 AB isotypes. There was no evidence of other diseases, including malignancy. Brain MRI revealed non-specific cortical FLAIR/T2 signal hyperintensities and cEEG showed extreme delta brush (EDB) events. The patient entered a 6 wk clinical trial with DSR in doses increased gradually from 1.5 to 4 g/day. This treatment was well tolerated and resulted in increased DSR serum levels from 0.93 to 103.1 �¼M. No side effects were registered. Positive and Negative Syndrome Scale (PANSS) symptom clusters improved and PANSS total score decreased by 34%. The quality of life of the patient, as assessed by schizophrenia quality of life scale (SQLS) improved considerably (37% total score reduction). At 6 wks, cEEG showed significant reduction of EDB-type activity. This pilot investigation: 1) supports the hypothesis that a subgroup of treatment-resistant patients diagnosed with schizophrenia may suffer from an NMDAR-related autoimmune disorder; and 2) indicates that DSR may represent a novel type of treatment for these patients.
Uriel Heresco-Levy is a Full Professor of Psychiatry at Hadassah Medical School, Hebrew University and Director of the Psychiatry Department at Herzog Memorial Hospital, Jerusalem, Israel. He is a Member of the European College of Neuropsychopharmacology (ECNP) and Fellow of Collegium International Neuro- Psychopharmacologicum (CINP). He has conducted pioneer clinical trials with N-methyl-D-aspartate receptor (NMDAR) modulators, including glycine, D-serine and D-cycloserine and has published extensively on the role of NMDAR-mediated neurotransmission and D-serine in neuropsychiatric disorders. He is the inventor of patents focusing on the use of NMDAR-neurotransmission pharmacomodulation in Parkinson's disease, major depressive disorder and autoimmune NMDAR encephalopathies.
Email: urielh@ekmd.huji.ac.il