Last update 01 Nov 2024

LGI1 x GAD x NMDA receptor

Last update 01 Nov 2024

Basic Info

Related Targets

LGI1GADNMDA receptor

Drugs associated with LGI1 x GAD x NMDA receptor

S52.006

Target

GAD x LGI1 x NMDA receptor

Mechanism

GAD inhibitors [+2]

Active Org.

Heinrich-Heine-Universität Düsseldorf

Originator Org.

Heinrich-Heine-Universität Düsseldorf

Active Indication

Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with LGI1 x GAD x NMDA receptor

100 Translational Medicine associated with LGI1 x GAD x NMDA receptor

0 Patents (Medical) associated with LGI1 x GAD x NMDA receptor

Literatures (Medical) associated with LGI1 x GAD x NMDA receptor

01 Apr 2016·Neurology Neuroimmunology & NeuroinflammationQ1 · MEDICINE

Immunoadsorption therapy in autoimmune encephalitides

Q1 · MEDICINE

ArticleOA

Author: Bien, Christian G. ; Brand, Marcus ; Münstermann, Dieter ; Dogan Onugoren, Müjgan ; Melzer, Nico ; Pavenstädt, Hermann ; Thölking, Gerold ; Valentin, Rainer ; Bulla-Hellwig, Michael ; Wiendl, Heinz ; Bien, Corinna ; Golombeck, Kristin S. ; Abu-Tair, Mariam ; Lohmann, Hubertus

OBJECTIVEIt was hypothesized that in encephalitides with autoantibodies directed to CNS surface antigens an antibody-removing intervention might speed up recovery.METHODSThe outcome of autoimmune encephalitis in 19 patients with antibodies against surface antigens (leucine-rich, glioma inactivated 1 [LGI1], n = 3; contactin-associated protein-2 [CASPR2], n = 4; NMDA receptor [NMDAR], n = 7) and intracellular antigens (glutamic acid decarboxylase [GAD], n = 5) after immunoadsorption in addition to corticosteroid therapy was evaluated retrospectively. Modified Rankin scale (mRS) scores and data on seizures, memory, and antibody titers directly after immunoadsorption (early follow-up) and after a median of 4 months (late follow-up) were compiled.RESULTSImmediately after immunoadsorption, 9 of 14 patients with antibodies against LGI1, CASPR2, or NMDAR (64%), but none with GAD antibodies, had improved by at least one mRS point. Five of the 7 patients with LGI1 or CASRP2 antibodies had become seizure-free, and 2 patients with NMDAR antibodies had a memory improvement of more than 1 SD of a normal control population. At late follow-up, 12 of 14 patients with surface antibodies had improved (86%), and none of the patients with GAD antibodies.CONCLUSIONSIt is suggested that addition of immunoadsorption to immunosuppression therapy in patients with surface antibodies may accelerate recovery. This supports the pathogenic role of surface antibodies.CLASSIFICATION OF EVIDENCEThis study provides Class IV evidence that immunoadsorption combined with immunosuppression therapy is effective in patients with autoimmune encephalitis with surface antibodies.

01 Oct 2013·Journal of Neurology

Anti-GAD antibody ocular flutter: expanding the spectrum of autoimmune ocular motor disorders

Letter

Author: Lucio Santoro ; Raffaele Dubbioso ; Fiore Manganelli ; Rosa Iodice ; Marcello Esposito ; Vincenzo Marcelli

Antibodies directed against glutamic acid decarboxylase (GAD) have been described in patients with progressive cerebellar ataxia [1] and in a few patients affected by primarily oculomotor disorders [2]. The abnormal eye movements described with anti-GAD antibodies, so far, range from nystagmus (up/down-beat, periodic alternating nystagmus) [2, 3] to opsoclonus [4], but ocular flutter has never been reported. A 69-year-old woman was admitted to our hospital for a 10-month progressive oscillopsia, blurred vision and gait imbalance with significant impairment of daily activities (such as reading a book, watching television and leaving home alone). Neurological examination showed ocular flutter, characterized by intermittent bursts of horizontal conjugate saccades without an intersaccadic interval. The eye oscillations were independent of eye position and occurred during fixation (voluntary and guided changes in gaze position), regardless of gaze direction, with eyes open or closed. The patient had full range of eye motion and did not report diplopia. Unsteadiness with severe retropropulsion was also evident. The remaining neurologic examination was normal. Analysis of ocular movements using video-oculography revealed bursts of rapid horizontal, symmetric movements without intersaccadic interval (Fig. 1a). Results of electrophysiological examinations, such as somatosensory and visual evoked potentials, nerve conduction study and electroencephalography, were normal. Routine blood cell counts and biochemistry were normal. Serological tests, cultures, and polymerase chain reactions performed on blood and cerebrospinal fluid (CSF) samples were negative for viral, bacterial, and fungal infections. Brain magnetic resonance imaging showed no abnormality. Results of screening examinations for neoplasms, including abdominal ultrasonography, computed tomography of the abdomen and chest, as well as whole-body positron emission tomography, were all unremarkable. CSF examination revealed normal protein concentration and no cells, isoelectric focusing showed two oligoclonal bands and the immunoglobulin G index was within the normal range. The patient tested negative for anti-gliadin, paraneoplastic antibodies (anti-Ri, anti-Hu, anti-Yo, antiMa2, anti-CV2 and anti-amphiphysin), anti-LGI1, antiCaspr2, antiganglioside Q1b and anti-NMDA receptor in the serum and CSF. Antibodies against GAD65 were measured by radioimmunoassay. GAD65 antibody titre was increased in serum (2,378 IU/mL, normal value \1 IU/mL) and in CSF (55.7 IU/mL, normal value \1 IU/mL), with an intrathecal synthesis index of 10.64 (normal range 0.7–1.3). An intravenous immunoglobulin (IVIg) treatment (400 mg/kg/day for 5 days) in six cycles once a month was started. The symptoms gradually resolved and continued to improve after the last administration of IVIg and at the same time serum GAD65 antibody titre decreased significantly (Fig. 1c). To avoid clinical relapses, azathioprine 200 mg orally daily was added to the last cycle of IVIg (Fig. 1c). R. Dubbioso F. Manganelli R. Iodice M. Esposito L. Santoro (&) Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘‘Federico II’’, Via Sergio Pansini, 5, 80131 Naples, Italy e-mail: lusantor@unina.it

01 Jan 2013·Rinsho Shinkeigaku

Autoimmune Encephalitis and its related-disorders

Review

Author: Yoneda, Makoto

Over the last few years, various autoantibodies against cell surface or intracellular antigens were identified in association with several forms of encephalitis, i.e. autoimmune encephalitis. Immunoprecipitaion and sequence analysis of the target protein (proteomics) provided the identification of the antigens corresponding to autoantibodies in autoimmune encephalitis. Appropriate preparation of antigens (synthesized peptides, or recombinant proteins prepared in E.coli or cultured mammalian cells) and assay systems (immunoblot, ELISA, immunoprecipitation or cell-based assay) should be selected for detection of each autoantibodies.Limbic encephalitis characterized by psychosis, dementia, seizures and abnormal movements is a common form of autoimmune encephalitis. Autoantibodies against the NMDA receptor, the AMPA receptor or the VGKC complex (LGI1 and Caspr2) were identified in limbic encephalitis with or without tumor association. Especially, limbic encephalitis associated with anti-NMDA receptor and ovarian teratoma became a distinct neurologic disorder to date.The intracellular antigens are also involved in several forms of encephalitis. Cerebellar ataxia is a common form of autoimmune encephalitis (cerebellits). The autoimmune cerebellar ataxia consists of paraneoplastic ataxia (anti-Yo etc.), anti-GAD-autoantibodies associated ataxia, gluten ataxia (anti-gliadin) and ataxic form of Hashimoto's encephalitis (anti-NAE).The early and accurate diagnosis of autoimmune encephalitis is important because most patients show responses to immunotherapy.

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