Munich Cluster for Systems Neurology (SyNergy)’s Post

Blood Biomarker Reveals Signs of Multiple Sclerosis Years Before #MS is a chronic inflammatory disease of the central nervous system affecting nearly a million Americans. There is no cure, so treatments aim to manage symptoms and slow disease progression. Scientists at UCSF discovered that in about one in ten cases of MS, the body produces specific antibodies against its own proteins years before symptoms appear. These autoantibodies may bind to human cells and common pathogens, potentially explaining MS's immune attacks on the brain and spinal cord. Published in Nature Medicine, the findings offer hope for early MS detection through a simple blood test. This could allow for earlier intervention and better treatment outcomes. Using a technique called PhIP-Seq, the researchers analyzed blood samples from MS patients collected both before and after diagnosis. They found that 10% of MS patients had high levels of autoantibodies years before diagnosis, with patterns resembling those found in common viruses like Epstein-Barr Virus (EBV). #Biotechnology #MSResearch #EarlyDetection #Autoantibodies #Neuroscience #ChronicIllness #HealthScience #MedicalBreakthrough #DiseaseProgression #InflammatoryDisease #UCSFScientists

There is the brain-gut axis…and now there looks to be a brain-heart axis as well. Though the brain-heart axis, is more ‘immune cell’ talk than ‘peptide’ talk. Researchers wanted to see what link there was between the brain and heart—in regards to post-stroke chronic co-morbidities (such as cognitive impairment & dementia, post-stroke depression, cardiac events, persistent vascular inflammation & stroke-induced metabolic disturbances) could lead to development of further acute brain injuries. Using a mouse model and single cell mRNA sequencing of myeloid cells isolated from blood & peripheral organs, they found that there is a pro-inflammatory change in monocytes & macrophages in the organs—and are detectable up to three months post stroke. This pro-inflammatory change detected in the heart corresponded to cardiac fibrosis & dysfunction. When they blocked a specific pro-inflammatory cytokine, they were able to prevent the post-stroke cardiac dysfunction in mice. Whether or not the same can be said for human patients…that’s the next big question. It will be interesting to see if blocking this specific pro-inflammatory cytokine is able to reduce secondary health problems that can occur when someone suffers a stroke (and could potentially lead to them suffering from other strokes later). #animalmodels #cellbiology #immunology #stroke #cardiacissues #mRNAseq #singlecellsequencing #epigenetics #memorycells #cytokines 

Innate immune memory after brain injury drives inflammatory cardiac dysfunction From Cell: Highlights: •Acute brain ischemia leads to persistent innate immune memory •Innate immune memory causes chronic post-stroke cardiac dysfunction •IL-1β induces post-stroke-trained immunity through epigenetic modifications •Blocking IL-1β or monocyte recruitment prevents cardiac dysfunction This research is crucial because it expands our understanding of stroke's impact beyond the immediate brain injury. Stroke survivors often face chronic comorbidities that significantly affect their quality of life and prognosis. Traditionally, treatment has focused on the brain, but this study reveals that the consequences extend to multiple organs over a prolonged period, driven by a common immunological cause. The study identifies myeloid innate immune memory as a cause of remote organ dysfunction after stroke. Using single-cell sequencing, researchers discovered persistent pro-inflammatory changes in monocytes/macrophages in various organs, including the heart, up to three months post-injury. These changes lead to cardiac fibrosis and dysfunction in both mice and stroke patients, indicating a direct link between brain injury and heart disease. IL-1β, a key pro-inflammatory cytokine, was found to drive these epigenetic changes in innate immune memory. Remarkably, these changes could be transferred to naive mice, inducing cardiac dysfunction, illustrating the systemic impact of stroke-induced immune alterations. Therapeutically, the study demonstrates that neutralizing IL-1β or blocking pro-inflammatory monocyte trafficking with a CCR2/5 inhibitor can prevent post-stroke cardiac dysfunction. This suggests that immune-targeted therapies could potentially prevent various IL-1β-mediated comorbidities, offering a comprehensive approach for secondary prevention in stroke survivors. https://lnkd.in/gHGGkQwj #StrokeResearch #Immunology #ChronicComorbidities #MyeloidMemory #IL1β #CardiacHealth #SingleCellSequencing #Epigenetics #Inflammation #SecondaryPrevention #Immunotherapy #HeartDisease #HealthInnovation #MedicalResearch #StrokeSurvivors #ProInflammatory #MedicalBreakthrough #SystemicImmunity #PostStrokeCare #ScientificDiscovery

🧠💡 Modeling Parkinson's disease pathology in human dopaminergic neurons by sequential exposure to α-synuclein fibrils and proinflammatory cytokines🧬 New research sheds light on how Lewy bodies (LBs), a hallmark of PD, may form. Using iPSC-derived human dopaminergic (DA) neurons, the study shows that α-synuclein preformed fibrils (PFFs) can lead to LB-like inclusions, but only when combined with immune challenges like interferon-γ or interleukin-1β. Here are the key insights: • Immune-triggered lysosomal dysfunction is a major factor, with interferon-γ impairing lysosome function, contributing to LB formation. • LAMP2 knockdown or GBA knockout, along with PFF exposure, further drives inclusion formation. • The LB-like inclusions are membrane-bound, pointing to issues beyond the cytoplasm—potentially involving autophagy dysfunction. This research strengthens the link between immune system dysregulation and PD pathology, raising important questions for therapeutic interventions. Thoughts on this connection between immunity and neurodegeneration? 🤔 https://lnkd.in/gpZDJpyJ 🧩 #ParkinsonsDisease #LewyBodies #Neurodegeneration #StemCellResearch #Immunology

I am thrilled to present our work on the Sanofi Disease Expansion Engine (SANDIE) platform as a poster at the Federation of Clinical Immunology Societies (FOCIS) 2024 in San Francisco on June 19th. For this poster, we present a drug repurposing framework utilizing SANDIE for cross-TA expansion, specifically targeting neuroinflammatory diseases with immune and inflammation-related drugs. The poster, titled "Data-driven Positioning of Immune and Inflammation Related Drugs to Target Neuroinflammation Diseases," showcases our innovative approach and findings. Please reach out to me or stop by the poster #W182 if you are attending FOCIS and are interested in our work. #FOCIS2024 #FOCIS #Sanofi #SANDIE #DrugRepurposing #IndicationPositioning #LCM #IndicationExpansion #TAExpansion #Immunology #Inflammation #Neuroinflammation #Neurology Shameer Khader, Ph.D, MPH Emanuele de Rinaldis Clément Chatelain Dimitry Ofengeim Pablo Sardi Anna Blazier Samuel Lessard Travis Ahn-Horst Mahasweta Bhattacharya, Ph.D. Franck Rapaport Heming Xing Zhaohui Du Zhipeng Liu Leonardo Rodrigues

As FOCIS 24 is progressing in California - please do check out our emerging immunoscience work being presented. Tejaswi Iyyanki and Clément Chatelain will be sharing about our efforts on building SANDIE - Sanofi Disease Indication Engine - A unified data + AI + Analytics capabilities for seamless assessments of drug/targets for indication expansion studies, life-cycle management and digital drug repurposing/ repositioning investigations. Out beyond the technical KPIs and expansive data coverage across multiple therapeutic areas, SANDIE is emerging a tour-de-force in identifying "pipelines-in-a-product" with 3x shorter timelines than industry standards. It is amazing to see that Sanofi continues its thoughtful investment in data + AI + Analytics to optimize our pipeline and portfolio. Special thanks to Emanuele de Rinaldis for sponsoring this initiative and all of our TA leaders and cluster heads for seamless collaboration. 💊 W182: Data-driven Positioning of Immune and Inflammation Related Drugs to Target Neuroinflammation Diseases 🧬 Tu148 : Enhancing Drug Indication Expansion in Immunology with Sanofi Genetic Data Lake #Immunoscience #AI #DataScience #PrecisionMedicine #MultiModal #bigdata #TechBio #Biotech #pharma #ML #transcriptomics #genomics #proteomics #GenAI #Bioinformatics #Multiomics #MachineIntelligence #PredictiveModeling #Sanofi #IamSanofi #Sanofian #PharmaTech #ComputationalBiology #phenomics #pipeline #portfolio

☀Favourite paper of the day ☀ IgG Immune Complexes Break Immune Tolerance of Human Microglia Research has revealed the crucial role of IgG complexes in the pathology of multiple sclerosis (MS). Post-mortem analysis of brain donors with MS demonstrates the binding of IgG to myelin, thereby intensifying the microglial response to microbial stimuli. A comprehensive understanding of these mechanisms could improve our understanding of demyelination and inflammation associated with MS. #MultipleSklerosis #Microglia #IgG 

Did you know that people with aHUS may have medical care led by different specialty fields?   Atypical HUS can be categorized as a hematologic disease, with reduced red blood cell & platelet counts. #aHUS #hematology #nephrology #immunology #TMA #complement #cmTMA 

#NeuroInflammation | #TertiaryLymphoidStructures in the #CNS 🧠 | OPEN ACCESS #Neuroimmunology Review Now Breaking Online at Cell Press | Roles of #TLSs in: | #MultipleSclerosis | #Glioma | #Stroke | #Infection | & More | Tertiary lymphoid structures (TLSs) frequently occur at sites of chronic inflammation. A more advanced stage of multiple sclerosis (MS) has been associated with certain TLSs. However, tumor-associated TLSs have been shown to correlate with a greater treatment response rate and a better prognosis in glioma mouse models. In this review*, the authors evaluate the clinical significances of TLSs in prognosis and treatment response, as well as the status of TLS-directed therapies targeting alternative biochemical pathways in various central nervous system (CNS) disorders. Potential molecular mechanisms underlying the development of TLSs are also discussed. Exploring these areas may provide an essential understanding of the processes behind disease advancement, uncover new therapeutic objectives, and detect biomarkers that forecast disease progression and treatment efficacy. *https://lnkd.in/e6prWPqA Celentyx Ltd #neuroinflammation #drugdiscovery www.celentyx.com Professor Nicholas Barnes PhD, FBPhS Omar Qureshi Catherine Brady FIGURE | Mechanisms underlying the formation of tertiary lymphoid structures (TLSs) | Crosstalk between immune and stromal cells has an essential role in the formation of TLSs, during which the binding of LTα1β2 to LTβ receptor (LTβR) leads to the release of many chemokines and adhesion molecules to recruit lymphocytes from high endothelial venules (HEVs) and form distinct T and B cell zones | Abbreviations: CCL, chemokine (C-C motif) ligand; CXCL, chemokine (C-X-C motif) ligand; DC, dendritic cell; IL, interleukin; LT, lymphotoxin; LTi, lymphoid tissue inducer; TFH, T follicular helper; TH17 cell, T helper cell 17.; VEGFC, vascular endothelial growth factor C |

 Breakthrough in Understanding Cytokine Storm Syndrome (CSS) 🌟 Cytokine Storm Syndrome (CSS) is a life-threatening condition where the immune system goes into overdrive, causing severe inflammation and organ damage. This hyperactivity can be triggered by infections, therapies, or autoimmune conditions. However, the interaction between different immune cells during CSS has been unclear—until now. 🔬 New Discovery: Neutrophils to the Rescue! 🔬 Recent research has uncovered a protective role for neutrophils, a type of white blood cell, in managing CSS. Using cutting-edge imaging techniques, scientists observed that neutrophils send tiny packets called extracellular vesicles to macrophages, another type of immune cell. These packets help calm the inflammatory storm by reducing the production of harmful substances. 💡 How Does It Work? 💡 Neutrophil Packets: Neutrophils release these extracellular vesicles, which travel to macrophages in organs like the liver and spleen. Anti-Inflammatory Boost: Inside the macrophages, these vesicles increase levels of itaconate, a powerful anti-inflammatory molecule. Inflammation Control: This process helps macrophages switch to a mode that reduces inflammation, protecting the body from severe damage. 🔗 Broader Implications 🔗 This groundbreaking discovery highlights a new way that neutrophils and macrophages communicate to control inflammation. It opens up promising avenues for treating CSS, potentially saving lives by targeting this cell-to-cell communication pathway. Understanding this interaction could lead to revolutionary therapies for CSS and other inflammatory conditions. https://lnkd.in/dEEEfqjb