Myelin Oligodendrocyte Glycoprotein Research Articles

Enhancing Lesion Detection in Inflammatory Myelopathies: A Deep Learning-Reconstructed Double Inversion Recovery MRI Approach.

The imaging of inflammatory myelopathies has advanced significantly over time, with MRI techniques playing a pivotal role in enhancing lesion detection. However, the impact of deep learning (DL)-based reconstruction on 3D double inversion recovery (DIR) imaging for inflammatory myelopathies remains unassessed. This study aims to compare acquisition time, image quality, diagnostic confidence, and lesion detection rates among sagittal T2WI, standard DIR, and DL -reconstructed DIR in patients with inflammatory myelopathies. In this observational study, patients diagnosed with inflammatory myelopathies were recruited between June 2023 and March 2024. Each patient underwent sagittal conventional turbo spin-echo sequences and standard 3D DIR (T2WI and standard 3D DIR used as references for comparison), followed by an undersampled accelerated DIRDL examination. Three neuroradiologists evaluated the images using a four-point Likert scale (from 1 to 4) for overall image quality, perceived signal-tonoise ratio, sharpness, artifacts, and diagnostic confidence. The acquisition times, and lesion detection rates were also compared between the acquisition protocols. A total of 149 participants were evaluated (mean age 40.6 ± 16.8 years; 71 females). The median acquisition time for DIRDL was significantly lower than for standard DIR (298 seconds [interquartile range (IQR), 288-301] vs 151 seconds [IQR, 148-155]; P < 0.001), showing a 49%time reduction. DIRDL images scored higher in overall quality, perceived signal-to-noise ratio, and artifact noise reduction (all P < 0.001). There were no significant differences in sharpness (P = 0.07), or diagnostic confidence (P = 0.06) between the standard DIR and DIRDL protocols. Additionally, DIRDL detected 37% more lesions compared to T2WI (300 vs. 219; P < 0.001). DIRDL significantly reduces acquisition time and improves image quality compared to standard DIR without compromising diagnostic confidence. Additionally, DIRDL enhances lesion detection in patients with inflammatory myelopathies, making it a valuable tool in clinical practice. These findings underscore the potential for incorporating DIRDL into future imaging guidelines. DL = deep learning; DIR = double inversion recovery; IQR = interquartile range; MS = multiple sclerosis; AQP4+NMOSD = AQP4-IgG positive neuromyelitis optica spectrum disorders; MOG = myelin oligodendrocyte glycoprotein; MOGAD = MOG antibody-associated diseases.

Secondary organising pneumonia associated to COVID-19 infection in patients with central nervous system inflammatory demyelinating diseases treated with anti-CD20 therapies.

Organizing pneumonia (OP), an interstitial lung disease, has been observed in patients with inflammatory demyelinating diseases (IDDs) treated with anti-CD20, particularly after COVID-19, but data are limited. To provide a detailed characterization of COVID-19-associated OP in IDD patients treated with anti-CD20. Bi-centric retrospective cohort study including patients with multiple sclerosis (MS), aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD), and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) who received anti-CD20 and were diagnosed with COVID-19-associated OP between March 2020 and October 2023. Nineteen patients were included (mean age 46.8 years; 52.6% female; 63% rituximab, 37% ocrelizumab). Sixteen had MS, two MOGAD, and one AQP4 + NMOSD. Intermittent fever was the predominant symptom. Hospitalization occurred in all but one patient, without fatalities. Chest CT consistently showed OP patterns. Thirteen patients had positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR in bronchoalveolar lavage. Treatments included corticosteroids, antivirals, monoclonal antibodies, and convalescent plasma. Fourteen patients postponed infusions; nine resumed post-recovery (median 11.9 months), two switched due to hypogammaglobulinemia, and three stopped. After a mean follow-up of 1.5 years, lung abnormalities and clinical manifestations resolved in 18 patients; however, 13 experienced long-COVID. In anti-CD20-treated patients with recurrent fever and distinctive CT features, COVID-19-associated OP should be considered.

Case report: Infectious mononucleosis with bilateral retinal haemorrhages under myelin oligodendrocyte glycoprotein antibody-associated disease

BackgroundBilateral optic neuritis associated with optic disc swelling is a common feature of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, extensive deep retinal haemorrhages have not been described in the context of MOG-associated optic neuritis. Here, we report a case of infectious mononucleosis with marked binocular peripapillary and perivascular haemorrhages as well as extensive deep retinal haemorrhages in the presence of MOGAD.Case reportA 39-year-old Chinese woman presenting with subacute binocular vision reduction with no light perception was diagnosed with MOGAD. Fundus examination revealed the presence of binocular peripapillary and perivascular haemorrhages as well as extensive deep retinal haemorrhages with severe optic disc swelling greater in the right eye than in the left and dilated and tortuous retinal venules. The patient tested positive for the Epstein–Barr virus (EBV) antigen (595 U/mL) and the EBV capsid antigen (&amp;gt;750 U/mL). She had a fever and right upper quadrant abdominal pain, and a doctor determined splenomegaly 1 week before the onset of orbital pain and decreased vision acuity. Medical history and laboratory tests indicated the presence of concurrent infectious mononucleosis. Other investigational indicators of retinal haemorrhages, including hypertension, diabetes mellitus, vascular disease, systemic lupus erythematosus, metabolic disease, and renal or liver dysfunction, were absent.DiscussionThis case suggests that retinal haemorrhage is a possible complication of infectious mononucleosis in the presence of MOGAD.

Barriers in Healthcare to the Use of Optical Coherence Tomography Angiography in Multiple Sclerosis.

Optical coherence tomography angiography (OCT-A) is a state-of-the-art imaging technique for the retinal vasculature to accurately segment the capillary network and assign it to retinal layers. OCT-A is a promising technique to better understand neurological diseases with visual system manifestations, such as multiple sclerosis (MS), and to identify and characterize vascular biomarkers. Initial studies suggested vascular changes in MS and its differential diagnoses such as myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD). Here we review clinical and technical aspects of OCT-A imaging and discuss the potential for the MS field as well as barriers that need to be overcome before OCT-A can be established in clinical application.

Cerebrospinal fluid neurofilament light chain levels in children with acquired demyelinating syndrome

ObjectiveTo study the cerebrospinal fluid (CSF) neurofilament light chain (NfL) in pediatric acquired demyelinating syndrome (ADS) and its association with factors of laboratory and imaging results.MethodsWe analyzed clinical data from children with ADS collected from May 2020 to January 2021 at the Department of Neurology of Guangzhou Women and Children's Medical Center. Enzyme-linked immunosorbent assays were used to detect the CSF NfL of patients.ResultsThirty pediatric ADS patients (17 male, 13 female) were included in the study. The most frequent diagnosis was uncategorized ADS (36.7%, 11/30), followed by acute disseminating encephalomyelitis (ADEM) (23.3%, 7/30), myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD) (20.0%, 6/30), NMO (6.7%, 2/30), multiple sclerosis (MS) (6.7%, 2/30), and neuromyelitis optic spectrum disorders (NMOSD) (6.7%, 2/30). The median CSF NfL for the first time was 7,425.28 pg/ml (interquartile range, 1,273.51, &amp;gt;10,000 pg/ml). CSF NfL increase over normal value (&amp;lt;290.00 pg/ml for people younger than 30 years old) was seen in 98.7% of patients. Patients were divided into uncategorized ADS, ADEM, MOGAD, and MS/NMO/NMOSD groups, with no significant difference in CSF NfL between each group. The CSF NfL positively correlated with the immunoglobulin (Ig) G (ρ = 0.473) and IgE (ρ = 0.366). However, the CSF NfL did not correlate with CSF white blood count and CSF protein. Furthermore, there was no significant difference between patients with oligoclonal bands positive and without. The CSF NfL negatively correlated with interferon γ (ρ = −0.501), CD45 + CD3+ T (ρ = −0.466), CD45 + CD3 + CD4+ T (ρ = −0.466), and CD45 + CD3 + CD8+ T cells (ρ = −0.521). However, it did not correlate with CD45 + CD19+ B cells. CSF NfL in patients with cerebral white matter lesions in MRI was higher than in patients without. Moreover, the CSF NfL positively correlated with the number of brain MRI locations (ρ = 0.362). Nine patients underwent multiple detections of CSF NfL, and their CSF NfL for the last detection was not significantly different from the first.ConclusionsThe CSF NfL increases significantly in pediatric ADS, and it can be a biomarker of neuro-axonal injury and a good indication of the extent of lesions.

Antigen-specific modulation of chronic experimental autoimmune encephalomyelitis in humanized mice by TCR-like antibody targeting autoreactive T-cell epitope.

The development and application of human TCR-like (TCRL) antibodies recognizing disease-specific MHC-peptide complexes mayprove asan important tool for basic research and therapeutic applications. Multiple sclerosis is characterized by aberrant CD4 T-cell response to self-antigens presented by MHC class II molecules. This led us to select a panel of TCRL Abs targeting the immunodominant autoantigenic epitope MOG35-55 derived from myelin oligodendrocyte glycoprotein (MOG) presented on HLA-DR2, which is associated with multiple sclerosis (MS). We demonstrate that these TCRL Abs bind with high specificity to human HLA-DR2/MOG35-55-derived MHC class II molecules and can detect APCs that naturally present the MS-associated autoantigen in the humanized EAE transgenic mouse model. The TCRL Abs can block ex vivo and in vivo CD4 T-cell proliferation in response to MOG35-55 stimulation in an antigen-specific manner. Most significantly, administration of TCRL Abs to MOG35-55-induced EAE model in HLA-DR2 transgenic mice both prevents and regresses established EAE. TCRL function was associated with a reduction in autoreactive pathogenic T-cell infiltration into the CNS, along with modulation of activated CD11b+ macrophages/microglial APCs. Collectively, these findings demonstrate the combined action of TCRL Abs in blocking TCR-MHC interactions and modulating APC presentation and activation, leading to a profound antigen-specific inhibitory effect on the neuroinflammatory process, resulting in regression of EAE. Our study constitutes an in vivo proof of concept for the utility of TCR-like antibodies as antigen-specific immunomodulators for CD4-mediated autoimmune diseases such as MS, validating the importance of the TCR-MHC axis as a therapeutic target for various autoimmune and inflammatory diseases.

Apheresis therapies in MOGAD: a retrospective study of 117 therapeutic interventions in 571 attacks

BackgroundIncomplete attack remission is the main cause of disability in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Apheresis therapies such as plasma exchange and immunoadsorption are widely used in neuroimmunology. Data...

Brain-targeted autoimmunity is strongly associated with Long COVID and its chronic fatigue syndrome as well as its affective symptoms

IntroductionAutoimmune responses contribute to the pathophysiology of Long COVID, affective symptoms and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ObjectivesTo examine whether Long COVID, and its accompanying affective symptoms and CFS are associated with immunoglobulin (Ig)A/IgM/IgG directed at neuronal proteins including myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), synapsin, α + β-tubulin, neurofilament protein (NFP), cerebellar protein-2 (CP2), and the blood–brain-barrier-brain-damage (BBD) proteins claudin-5 and S100B. MethodsIgA/IgM/IgG to the above neuronal proteins, human herpes virus-6 (HHV-6) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were measured in 90 Long COVID patients and 90 healthy controls, while C-reactive protein (CRP), and advanced oxidation protein products (AOPP) in association with affective and CFS ratings were additionally assessed in a subgroup thereof. ResultsLong COVID is associated with significant increases in IgG directed at tubulin (IgG-tubulin), MBP, MOG and synapsin; IgM-MBP, MOG, CP2, synapsin and BBD; and IgA-CP2 and synapsin. IgM-SARS-CoV-2 and IgM-HHV-6 antibody titers were significantly correlated with IgA/IgG/IgM-tubulin and -CP2, IgG/IgM-BBD, IgM-MOG, IgA/IgM-NFP, and IgG/IgM-synapsin. Binary logistic regression analysis shows that IgM-MBP and IgG-MBP are the best predictors of Long COVID. Multiple regression analysis shows that IgG-MOG, CRP and AOPP explain together 41.7 % of the variance in the severity of CFS. Neural network analysis shows that IgM-synapsin, IgA-MBP, IgG-MOG, IgA-synapsin, IgA-CP2, IgG-MBP and CRP are the most important predictors of affective symptoms due to Long COVID with a predictive accuracy of r = 0.801. ConclusionBrain-targeted autoimmunity contributes significantly to the pathogenesis of Long COVID and the severity of its physio-affective phenome.

Dietary Intervention with Omega-3 Fatty Acids Mitigates Maternal High-Fat Diet-Induced Behavioral and Myelin-Related Alterations in Adult Offspring.

Maternal high-fat diet (HFD) during pregnancy and lactation induces depression- like phenotype and provokes myelin-related changes in rat offspring in the prefrontal cortex (PFCTX), which persist even to adulthood. Due to the plasticity of the developing brain, it was decided to analyze whether depressionlike phenotype and myelin-related changes in the early lifetime induced by maternal HFD (60% energy from fat) could be reversed by the omega-3 fatty acid-enriched diet (Ω3D) given from the postweaning period until adulthood (63rd day of life) in offspring. We analyzed the effect of post-weaning Ω3D on the depressive-like phenotype (assessed by the forced swimming test) and myelin-related changes (measured using RT-qPCR, ELISA, and immunofluorescence staining) in the PFCTX of adult offspring. Ω3D reversed increased immobility time in adult offspring induced by maternal HFD, without affecting the animals' locomotor activity. Molecularly, Ω3D normalized the reduced expression levels of myelin-oligodendrocyte glycoprotein (MOG), as well as myelin and lymphocyte protein (MAL) in males and MOG in females in the PFCTX, changes initially induced by maternal HFD. Additionally, Ω3D normalized the quantity of oligodendrocyte precursor cells and mature oligodendrocytes in the prelimbic, infralimbic, and cingulate cortex in males, which were reduced following maternal HFD exposure. In females, the Ω3D effect was less pronounced, with normalization of oligodendrocyte precursors occurring only in the infralimbic cortex. These findings suggest that Ω3D may play a significant role in correcting behavioral and neurobiological changes caused by adverse prenatal conditions.

Evaluation of Brain and Spinal Cord Lesions and Cerebrospinal Fluid Analysis in Detecting Demyelinating Diseases in Patients with Optic Neuritis

ABSTRACT Optic neuritis can be an early sign of demyelinating diseases like multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases (MOGAD). We investigated the presence or absence of head and spinal cord lesions on magnetic resonance imaging (MRI) and assessed whether cerebrospinal fluid (CSF) tests are useful in detecting demyelinating disease in patients with first diagnosed optic neuritis. We conducted a retrospective study of 111 patients (47 idiopathic, 19 NMOSD, 16 MOGAD, 16 MS, 6 optic neuritis with cerebral lesions but that does not meet the McDonald’s criteria for MS (ON+)), and 7 chronic relapsing inflammatory optic neuropathy) diagnosed with optic neuritis without cerebral or spinal symptoms. Patients underwent evaluations including orbital, head, and spine MRI, along with CSF analysis. Among the 111 patients, 20 (35.1%: 4 NMOSD, 4 MOGAD, 7 MS, and 6 ON+) exhibited intracerebral or spinal cord lesions. Twelve patients showed findings on both orbital and head MRI, while six had no orbital MRI findings except for optic neuritis but exhibited lesions on head MRI. Five patients had spinal lesions without intracerebral lesions. CSF analysis revealed positive oligoclonal bands and elevated myelin basic protein levels indicate the high likelihood with systemic inflammatory demyelinating diseases. Even in the absence of concomitant encephalitis or myelitis symptoms or a history of these conditions, MRI images of patients with optic neuritis sometimes reveal lesions in the brain or spinal cord. CSF abnormalities were indicative of systemic demyelinating disease presence, extending beyond MS to NMOSD and MOGAD.

A Simple Score (MOG-AR) to Identify Individuals at High Risk of Relapse After MOGAD Attack.

To identify predictors for relapse in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to develop and validate a simple risk score for predicting relapse. In China National Registry of Neuro-Inflammatory Diseases (CNRID), we identified patients with MOGAD from March 2023 and followed up prospectively to September 2023. The primary endpoint was MOGAD relapse, confirmed by an independent panel. Patients were randomly divided into model development (75%) and internal validation (25%) cohorts. Prediction models were constructed and internally validated using Andersen-Gill models. Nomogram and relapse risk score were generated based on the final prediction models. A total of 188 patients (comprising 612 treatment episodes) were included in cohorts. Female (HR: 0.687, 95% CI 0.524-0.899, p = 0.006), onset age 45 years or older (HR: 1.621, 95% CI 1.242-2.116, p < 0.001), immunosuppressive therapy (HR: 0.338, 95% CI 0.239-0.479, p < 0.001), oral corticosteroids >3 months (HR 0.449, 95% CI 0.326-0.620, p < 0.001), and onset phenotype (p < 0.001) were identified as factors associated with MOGAD relapse. A predictive score, termed MOG-AR (Immunosuppressive therapy, oral Corticosteroids, Onset Age, Sex, Attack phenotype), derived in prediction model, demonstrated strong predictive ability for MOGAD relapse. MOG-AR score of 13-16 indicates a higher risk of relapse (HR: 3.285, 95% CI 1.473-7.327, p = 0.004). The risk of MOGAD relapse seems to be predictable. Further validation of MOG-AR score developed from this cohort to determine appropriate treatment and monitoring frequency is warranted. CNRID, NCT05154370, registered December 13, 2021, first enrolled December 15, 2021.

High-yield production of recombinant human myelin oligodendrocyte glycoprotein in SHuffle bacteria without a refolding step

Experimental autoimmune encephalomyelitis (EAE) is a model for central nervous system (CNS) autoimmune demyelinating diseases such as multiple sclerosis (MS) and MOG antibody-associated disease (MOGAD). Immunization with the extracellular domain of recombinant human MOG (rhMOG), which contains pathogenic antibody and T cell epitopes, induces B cell-dependent EAE for studies in mice. However, these studies have been hampered by rhMOG availability due to its insolubility when overexpressed in bacterial cells, and the requirement for inefficient denaturation and refolding. Here, we describe a new protocol for the high-yield production of soluble rhMOG in SHuffle cells, a commercially available E. coli strain engineered to facilitate disulfide bond formation in the cytoplasm. SHuffle cells can produce a soluble fraction of rhMOG yielding >100 mg/L. Analytical size exclusion chromatography multi-angle light scattering (SEC-MALS) and differential scanning fluorimetry of purified rhMOG reveals a homogeneous monomer with a high melting temperature, indicative of a well-folded protein. An in vitro proliferation assay establishes that purified rhMOG can be processed and recognized by T cells expressing a T cell receptor (TCR) specific for the immunodominant MOG35–55 peptide epitope. Lastly, immunization of wild-type, but not B cell deficient, mice with rhMOG resulted in robust induction of EAE, indicating a B cell-dependent induction. Our SHuffle cell method greatly simplifies rhMOG production by combining the high yield and speed of bacterial cell expression with enhanced disulfide bond formation and folding, which will enable further investigation of B cell-dependent EAE and expand human research of MOG in CNS demyelinating diseases.

Recurrent late-onset neutropenia following treatment with different B cell-depleting strategies in multiple sclerosis.

As B cell-depleting therapies in multiple sclerosis (MS) have gained significant importance in the last several years, their long-term safety profile is of considerable clinical interest. Late-onset neutropenia (LON) is a rare, but potentially severe, adverse event that was first described in patients with rheumatic disorders under therapy with rituximab. Ofatumumab was approved in 2021 for the treatment of relapsing-remitting multiple sclerosis (RRMS). Neutropenia occurred in 0.2% of patients in clinical phase 3 trials, and to date, no cases of LON have been reported under ofatumumab treatment. Here, we report a case of repetitive symptomatic LON under ocrelizumab as well as ofatumumab treatment. Additionally, we review the literature on rare occurrences of LON in patients with MS, neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) undergoing B cell-depleting therapies, including rituximab, ocrelizumab, ofatumumab, inebilizumab, and ublituximab. In our case, the patient presented with repetitive symptomatic LON under ocrelizumab as well as ofatumumab treatment leading to febrile infections, subsequent use of antibiotics, and application of granulocyte-colony-stimulating factor. After repetitive episodes of LON under both B cell-depleting strategies, cladribine was subsequently initiated. A nine-month follow-up showed a normal neutrophil count and no evidence of disease activity. This case highlights the significance of symptomatic late-onset blood count changes under both ocrelizumab and ofatumumab and emphasizes the importance of continuous monitoring of the differential blood count under B cell-depleting treatment. This study was supported by the Deutsche Forschungsgemeinschaft (DFG; SFB CRC-TR-128 to F.Z., V.F., and S.B..; SFB 1080 and SFB CRC-1292 to F.Z..; and SFB/TRR 355 to S.B.) and the Hermann and Lilly Schilling Foundation (to S.B.).

FLAIR-Hyperintense Lesions in Anti-MOG-Associated Encephalitis with Seizures: A Case Report

Introduction: Myelin oligodendrocytic glycoprotein antibody-associated disease (MOGAD) is an immune-mediated demyelinating disorder of the central nervous system. We described, a case of encephalitis associated with anti-MOG antibodies with hyperintense lesions on FLAIR and seizures (FLAMES). Case Report: We report a case of a 5-year-old girl, with no significant personal or family history, who entered the emergency room with paroxysmal events and anarthria, in a febrile context. On neurological examination she presented right sided facial paresis and pyramidal signs on the right. Lumbar puncture (LP), showed pleocytosis, hyperproteinorrhaquia and the absence of oligoclonal bands. Electroencephalogram revealed encephalopathy and slow paroxysmal left frontal activity. The brain MRI detected hyperintense lesions, however, with an area of left frontal cortico-subcortical hyperintense signal on T2/FLAIR and diffusion restriction. Anti-MOG antibody was detected. These findings pointed to the diagnosis of FLAMES. She completed 7 days of methylprednisolone (30mg/kg/day), with a good response. On the day of discharge, a repeat EEG was conducted, demonstrating significant improvement compared to the initial one, with slightly slow wake and sleep patterns for her age, and no evidence of epileptic activity. She was assessed approximately four months post-hospitalisation and was found to be asymptomatic, with no focal neurological deficits. A further EEG was performed, which showed a structurally age-appropriate wake and sleep pattern with no abnormal graphoelements. Conclusion: We highlight a rare clinical-radiological entity, which is still poorly described, particularly in the paediatric population, known as FLAMES, with a favourable response to steroids. Early recognition and timely diagnosis of his condition improve clinical and therapeutic management and minimize neurological damage. Immediate initiation of appropriate treatment is important for achieving a favorable outcome.

Evaluation of arterial spin labeling in the diagnosis and monitoring of myelin oligodendrocyte glycoprotein-associated cerebral cortical encephalitis.

Myelin oligodendrocyte glycoprotein (MOG)-associated disorders are inflammatory demyelinating diseases of the CNS. Cerebral cortical encephalitis (CCE) is characterized by cortical fluid-attenuated inversion recovery hyperintensity with seizures and headaches. We report two cases of MOG antibody-associated CCE (MOG-CCE) evaluated using serial MRI sequences, including arterial spin labeling (ASL), pre- and posttreatment. In both patients, ASL demonstrated hyperperfusion correlating with disease activity, which normalized following steroid therapy. Our cases highlight the usefulness of ASL in early detection, monitoring, and assessment of treatment response in MOG-CCE.

Overview of emerging therapies for demyelinating diseases.

This paper provides an overview of autoimmune disorders of the central nervous system, specifically those caused by demyelination. We explore new research regarding potential therapeutic interventions, particularly those aimed at inducing remyelination. Remyelination is a detailed process, involving many cell types-oligodendrocyte precursor cells (OPCs), astrocytes, and microglia-and both the innate and adaptive immune systems. Our discussion of this process includes the differentiation potential of neural stem cells, the function of adult OPCs, and the impact of molecular mediators on myelin repair. Emerging therapies are also explored, with mechanisms of action including the induction of OPC differentiation, the transplantation of mesenchymal stem cells, and the use of molecular mediators. Further, we discuss current medical advancements in relation to many myelin-related disorders, including multiple sclerosis, optic neuritis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, transverse myelitis, and acute disseminated encephalomyelitis. Beyond these emerging systemic therapies, we also introduce the dimethyl fumarate/silk fibroin nerve conduit and its potential role in the treatment of peripheral nerve injuries. Despite these aforementioned scientific advancements, this paper maintains the need for ongoing research to deepen our understanding of demyelinating diseases and advance therapeutic strategies that enhance affected patients' quality of life.

In Silico Modeling of Myelin Oligodendrocyte Glycoprotein Disulfide Bond Reduction by Phosphine-Borane Complexes

Background: Neurodegenerative diseases can cause vision loss by damaging retinal ganglion cells in the optic nerve. Novel phosphine-borane compounds (PBs) can protect these cells from oxidative stress via the reduction of disulfide bonds. However, the specific targets of these compounds are unknown. Proteomic evidence suggests that myelin oligodendrocyte glycoprotein (MOG) is a potential target. MOG is of significant interest due to its role in anti-MOG optic neuritis syndrome. Methods: We used in silico modeling to explore the structural consequences of cleaving the extracellular domain MOG disulfide bond, both in isolation and in complex with anti-MOG antibodies. The potential binding of PBs to this bond was examined using molecular docking. Results: Cleaving the disulfide bond of MOG altered the structure of MOG dimers and reduced their energetic favorability by 46.13 kcal/mol. The energy profiles of anti-MOG antibody complexes were less favorable when the disulfide bond of MOG was reduced in the monomeric state by 55.21 kcal/mol, but the reverse was true in the dimeric state. PBs exhibited reducing capabilities with the MOG extracellular disulfide bond, with this best-scoring compound binding with an energy of −28.54 kcal/mol to the MOG monomer and −24.97 kcal/mol to the MOG dimer. Conclusions: These findings suggest that PBs can affect the structure of MOG dimers and the formation of antibody complexes by reducing the MOG disulfide bond. Structural changes in MOG could have implications for neurodegenerative diseases and anti-MOG syndrome.

MOG-specific CAR Tregs: a novel approach to treat multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system (CNS) with the immune system attacking myelin sheaths leading to neuronal death. While several disease-modifying therapies are available to treat MS, these therapies are not universally effective and do not stop disease progression. More personalized long-term treatment options that target specific aspects of the disease, such as reducing relapse frequency, delaying disability accumulation, and addressing symptoms that impact daily functioning, as well as therapies that can promote neuroprotection and repair are needed. Chimeric Antigen Receptor (CAR) Tcell therapies have revolutionized cancer treatment by intravenously (IV) administering a defined dose of T cells with high specificity provided by the CAR. An autologous CAR T cell therapy using suppressive regulatory T cells (Tregs) inducing long-lasting tolerance would be the ideal treatment for patients. Hence, we expanded the application of CAR-T cells by introducing a CAR into Tregs to treat MS patients. We developed a myelin oligodendrocyte glycoprotein (MOG)-specific CAR Treg cell therapy for patients with MS. MOG is expressed on the outer membrane of the myelin sheath, the insulating layer the forms around nerves, making it an ideal target for CAR Treg therapy. Our lead candidate is a 2nd generation CAR, composed of an anti-MOG scFv screened from a large human library. In vitro, we demonstrated CAR-dependent functionality and showed efficacy in vivo using a passive EAE mouse model. Additionally, the MOG-CAR Tregs have very low tonic signaling with a desirable signal-to-noise ratio resulting in a highly potent CAR. In summary our data suggest that MOG-CAR Tregs are a promising MS treatment option with the potential to induce long-lasting tolerance in patients.

Myelin oligodendrocyte glycoprotein antibody–associated disease with histopathologic features of primary CNS angiitis without demyelination: Case report and literature review

Primary angiitis of the central nervous system (PACNS) is a rare inflammatory disease that affects both small- and medium-sized vessels of the CNS, while myelin oligodendrocyte glycoprotein (MOG) antibody–associated disease (MOGAD) is a novel antibody-mediated inflammatory demyelinating disorder that causes damage to the myelin in CNS. We report a case diagnosed as MOGAD due to a history of recurrent myelitis, brain lesions, and positive anti-MOG, but the brain biopsy showed vasculitis without demyelination.

From Organotypic Mouse Brain Slices to Human Alzheimer’s Plasma Biomarkers: A Focus on Nerve Fiber Outgrowth

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by memory loss and progressive deterioration of cognitive functions. Being able to identify reliable biomarkers in easily available body fluids such as blood plasma is vital for the disease. To achieve this, we used a technique that applied human plasma to organotypic brain slice culture via microcontact printing. After a 2-week culture period, we performed immunolabeling for neurofilament and myelin oligodendrocyte glycoprotein (MOG) to visualize newly formed nerve fibers and oligodendrocytes. There was no significant change in the number of new nerve fibers in the AD plasma group compared to the healthy control group, while the length of the produced fibers significantly decreased. A significant increase in the number of MOG+ dots around these new fibers was detected in the patient group. According to our hypothesis, there are factors in the plasma of AD patients that affect the growth of new nerve fibers, which also affect the oligodendrocytes. Based on these findings, we selected the most promising plasma samples and conducted mass spectrometry using a differential approach and we identified three putative biomarkers: aldehyde-dehydrogenase 1A1, alpha-synuclein and protein S100-A4. Our method represents a novel and innovative approach for translating research findings from mouse models to human applications.