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8:30 am Virtual Coffee & Networking
9:00 am Chair’s Opening Remarks
Synopsis
A critical overview of the current status of knowledge in the field of neuroimmunology, setting the tone of openness, discussion and collaboration.
9:10 am Kick-Off Panel Discussion – Uncovering the Next Frontier of Neuroimmunology
Synopsis
- What have been the major advances in understanding neuroinflammation across CNS indications?
- Diving into specific challenges presented by various targets including microglia, astrocytes, TREM2 and STING. What would give us confidence that that target is translatable in a disease?
- What are common responses that we could target across these different diseases as well as what might be very distinct to particular diseases?
- What can we learn from the inflammatory response in the context of CNS injury?
- How have genetics and multi-omics analyses changed the way we study and develop therapies for CNS indications
Deploying Immuno-Neurology in Clinical Case Studies for CNS Diseases
9:50 am A Brain Penetrant Progranulin Biotherapeutic Rescues Lysosomal and Inflammatory Phenotypes in the Brain of Grn Knockout Mice
Synopsis
Session Details to Follow
10:15 am Small Molecule & Cell Therapies for Neurodegenerative Diseases
Synopsis
• Anti-inflammatory small molecules can dampen the pathogenic activation of microglia
• These anti-inflammatories are under evaluation in clinical trials on Alzheimer’s disease and Amyotrophic lateral sclerosis patients
• Engineered T cell therapies have the potential to dampen neuroinflammation and promote neuro-regeneration
10:40 am Psychedelics & Neuroinflammation: An Update from Ulysses Neuroscience
Synopsis
• Neuroinflammation in major depressive disorder and social isolation
• The interferon-alpha model model of neuroinflammation in mental disorders
• Effects of Ketamine and other psychedelics on neuroinflammation
11:05 am Live Speaker Q&A
11:20 am Morning Break & Speed Networking
Advances in Tools to Support the Mission of Harnessing Neuroimmune Pathways as Potential Drug Targets
12:00 pm Leveraging Genetics to Discover Immune-Modulating Targets for the Treatment of Neurodegenerative Diseases
Synopsis
• Overview of how we leverage genetics for drug discovery
• To what extent do we understand how genetics affects microglia biology? What have we recently uncovered in terms of microglial dynamics?
• Introduction of MS4 genetic locus, the MS4A protein family and more specifically, MSA4A
• Diving into our drug discovery process and what we know about this biology to date
• Deciphering the interactions between MSA4A and TREM 2
• Working towards MS4A4A as a therapeutic target
12:25 pm From Mapping TREM2 Signal Transduction to Downstream Pathway Biomarkers, Leveraging a Toolbox of Genetic & Pharmacological Perturbations
Synopsis
• TREM2 has been the focus of intense preclinical interest and an emerging area for early clinical development based on human lossof-function AD risk variants now connecting this microglial-enriched signaling hub with neurological disease
• Despite the surge of interest, functional insights have predominantly (though not exclusively) relied on genetic perturbations in cells and animals models of neurodegenerative diseases, putting the focal point of attention on the impact of loss-of-function.
• In this talk, I will share insights into (i) the validation of agonist tools to study TREM2 gain-of-function in various translationally relevant cellbased systems (ii) recent efforts to connect the intracellular cascade to extracellular responses in vitro and in vivo, as well as (iii) validate insights using TREM2 activating antibodies, with the collective goal of shedding further light on a preclinical functional hypothesis for the microglial TREM2 signaling axis
12:50 pm Live Speaker Q&A
1:10 pm Lunch Break
2:10 pm Microglia in Spacetime Continuum: Insights from Spatial Transcriptomics
Synopsis
• Advances in spatial transcriptomics to date and an overview of where we are now
• How can we best integrate RNA seq with data from proteomics and genomics to try to understand the new pathways that can be druggable and therefore beneficial for patients?
• How can we further drive our understanding of spatial transcriptomic and spatial proteomics?
• Implementing spatial transcriptomics in humans rather than mouse tissues
2:35 pm Metabolic Perturbations of Phagocytic Microglia in Alzheimer’s Disease Mouse Model
Synopsis
• Deep-phenotyping analysis of brain-sorted microglia reveals profound transcriptomic perturbations in line with the notion that microglia response is largely mediated by amyloid-β pathology in AD
• Accumulation of fibrillar Aβ in microglia is directly associated with a dramatic increase of various lipids,
• Implications for therapeutic avenues targeting microglia
3:00 pm Technology-Enabled Drug Discovery Platform Using Human Neuronal Models, Optogenetics & Machine Learning
Synopsis
• Induced pluripotent stem cell-derived neurons enable scalable, patientspecific disease models that can be used to capture complex disease phenotypes
• We utilize Optopatch, an all-optical electrophysiology platform to measure neuronal activity with single-cell and single action potential precision but with >10,000-fold higher throughput than manual patch clamp electrophysiology
• Machine learning of Optopatch data sets across thousands of neurons and hundreds of electrophysiological parameters enables identification of disease phenotypes that can be used as the basis for screening candidate therapeutics
• We have utilized this approach for discovery in inflammatory models of pain and other disease indications with the goal of identifying differentiated therapeutics and novel drug targets