Last update 01 Nov 2024

LGI1

Last update 01 Nov 2024

Basic Info

Synonyms

EPITEMPIN, Epitempin-1, EPT

+ [5]

Introduction

Regulates voltage-gated potassium channels assembled from KCNA1, KCNA4 and KCNAB1. It slows down channel inactivation by precluding channel closure mediated by the KCNAB1 subunit. Ligand for ADAM22 that positively regulates synaptic transmission mediated by AMPA-type glutamate receptors (By similarity). Plays a role in suppressing the production of MMP1/3 through the phosphatidylinositol 3-kinase/ERK pathway. May play a role in the control of neuroblastoma cell survival.

Drugs associated with LGI1

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

100 Translational Medicine associated with LGI1

0 Patents (Medical) associated with LGI1

853

Literatures (Medical) associated with LGI1

01 Nov 2024·Journal of the Neurological Sciences

Cerebrospinal fluid soluble CD27 is a sensitive biomarker of inflammation in autoimmune encephalitis

Article

Author: Sellebjerg, Finn ; Romme Christensen, Jeppe ; Nielsen, Claus Henrik ; Nissen, Mette Scheller ; Buhelt, Sophie ; Cobanovic, Stefan ; Illes, Zsolt ; Blaabjerg, Morten ; Kondziella, Daniel ; Mahler, Mie Reith

BACKGROUNDAutoimmune encephalitis (AE) comprises a group of rare, severe neuroinflammatory conditions. Current biomarkers of neuroinflammation are often normal in AE which therefore can be difficult to rule out in patients with seizures, cognitive and/or neuropsychiatric symptoms. Cerebrospinal fluid (CSF) soluble CD27 (sCD27) and soluble B-cell maturation antigen (sBCMA) have high sensitivity for neuroinflammation in other neuroinflammatory conditions. In this exploratory study we investigate the potential of sCD27 and sBCMA in CSF as biomarkers of neuroinflammation in AE.METHODSConcentrations of sCD27 and sBCMA were measured in CSF from 40 AE patients (20 patients were untreated (12 with anti-N-Methyl-d-Aspartate receptor antibodies (NMDA) and 8 with anti-Leucine-rich Glioma-Inactivated 1 antibodies (LGI1)), and 37 symptomatic controls (SCs).RESULTSCSF concentrations of sCD27 were increased in untreated NMDA AE patients (median 1571 pg/ml; p < 0.001) and untreated LGI1 AE patients (median 551 pg/ml; p < 0.05) compared to SCs (median 250 pg/ml). CSF sBCMA was increased in untreated NMDA AE patients (median 832 pg/ml) compared to SCs (median 429 pg/ml). CSF sCD27 and sBCMA correlated with the CSF cell count. Receiver operating characteristic curve analysis of untreated AE patients versus SCs showed an area under the curve of 0.97 for sCD27 and 0.76 for sBCMA.CONCLUSIONCSF sCD27 is a suitable biomarker of neuroinflammation in AE with an ability to discriminate patients with NMDA AE and LGI1 AE from symptomatic controls. CSF sCD27 may be suited for ruling out AE and other neuroinflammatory conditions in the early phase of the diagnostic work-up.

01 Nov 2024·Neurology Neuroimmunology & Neuroinflammation

A Multicenter Study

Article

Author: Elliott, Jonathan ; Miglis, Mitchell G ; Gan-Or, Ziv ; Ju, Yo-El S ; Schenck, Carlos H ; St Louis, Erik K ; Gagnon, Jean-Francois ; Howell, Michael ; Boeve, Bradley F ; Vorasoot, Nisa ; McKeon, Andrew ; During, Emmanuel H ; Forsberg, Leah K ; Ross, Owen A ; Videnovic, Aleksandar ; McLeland, Jennifer ; Bliwise, Donald L ; Avidan, Alon Y ; Postuma, Ronald ; Lim, Miranda M ; Singer, Wolfgang ; Criswell, Susan R ; Huddleston, Daniel E ; Pelletier, Amélie ; Fields, Julie A ; Davis, Albert A

BACKGROUND AND OBJECTIVESIdiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.METHODSParticipants were enrolled in the North American Prodromal Synucleinopathy cohort with polysomnography-confirmed iRBD, free of parkinsonism and dementia. Plasma samples were systematically screened for the autoantibodies IGLON5, DPPX, LGI1, and CASPR2 using plasma IgG cell-based assay. Positive or equivocal results were confirmed by repeat testing, plus tissue-based indirect immunofluorescence assay for IGLON5.RESULTSOf 339 samples analyzed, 3 participants (0.9%) had confirmed positive IGLON5 autoantibodies in the cell-based assay, which were confirmed by the tissue-based assay. An additional participant was positive for CASPR2 with low titer by cell-based assay only (of lower clinical certainty). These cases exhibited a variety of symptoms including dream enactment, cognitive decline, autonomic dysfunction, and motor symptoms. In 1 IGLON5 case and the CASPR2 case, evolution was suggestive of typical synucleinopathy, suggesting the possibility that findings were incidental. However, 2 participants with IGLON5 died before diagnosis was clinically suspected, with a final clinical picture highly suggestive of autoimmune disease.DISCUSSIONOur finding that nearly 1% of a large iRBD cohort may have a serious but potentially treatable autoantibody syndrome has important clinical implications. In particular, it raises the question of whether autoantibody testing for IGLON-5-IgG should be widely implemented for participants with iRBD, considering the difficulty in diagnosis of autoimmune diseases, their response to treatment, and the potential for rapid disease progression. However, any routine testing protocol will also have to consider costs and potential adverse effects of false-positive findings.TRIAL REGISTRATION INFORMATIONNCT03623672.

22 Oct 2024·Central Nervous System Agents in Medicinal Chemistry

Thiazolidine-4-one Analogues: Synthesis, In-Silico Molecular Modeling, and In-vivo Estimation for Anticonvulsant Potential

Article

Author: Shah, Kamal ; Mittal, Payal ; Dewangan, Hitesh Kumar ; Ghanghas, Deepak ; Arya, Girish Chandra ; Chaudhary, Aarti ; Sharma, Diksha

Background:Epilepsy is a critically deep-rooted CNS disorder affecting above 50 million people all over the world. Thus, a safe and effective treatment that proves its worth in this ailment is urgently needed. Thiazolidine-4-ones possess the molecules to be used as anticonvulsants. The thiazolidinedione is a cyclic analogue of thiosemicarbazides and thioureas as well as a (bio)isostere of hydantoin (imidazolidine-2,4-dione), which are recognized as novel anticonvulsant designs.Aim:This study aimed to develop and evaluate a novel thiazolidine-4-one derivative by three-component condensation in one pot reaction method.Methods:A novel thiazolidine-4-one derivative was formulated by three-component condensation. The selected OH (Alcohol) derivatives were found to be more potent; hence, a molecular docking study against a selected target LGI1 LRR domain was performed. Various analytical tests like FTIR and H1 NMR were accomplished. The FTIR was used to validate the existence of multiple functional moieties like C-S, O-H, C=O, C-N, N=O, C-NH, C-O in the wave region from 3075 cm-1 – 1236 cm-1 and H1 NMR was employed to ascertain if the synthesized analogues had the complete set of protons. Then, the anti-seizure activity of the selected compound was examined using PTZ models in mice at three successive doses, i.e., 25, 50, and 100mg/kg, and compared with standard ethosuximide.Results:The docking simulations were initiated using PyMOL after the binding site was determined and the receptor and ligand were suitably prepared. It showed higher binding frequency in comparison to the standard marketed drug Ethosuximide. FTIR and H1 NMR spectroscopy were used to characterize the chemical components. Numerous functional groups, including O-H (alcohol), C=O (ketones), N=O, C-NH, C-N, C-S, and C-O bending stretching, were visible in the synthesized molecule accordingly. The synthesized compound was effective in inhibiting the convulsions at the concentration of 100 mg/kg.Conclusion:The novel thiazolidine-4-one derivative showed promising activity and could be considered for further investigation and dosage form preparation.

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LGI1

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