9:00 am Chair’s Opening Remarks

How Can We Best Integrate Targets & Tools into Clinical Development Programs?

9:05 am Panel Discussion – Translation of Therapeutic Efficacy in Neuroinflammation: Importance of Identifying the Best Biomarkers & Relevant Models

Synopsis

• How should we develop an assay for each biomarker to better understand whether modulating our target impacts the activity of microglia?
• How do we leverage our translational tools to measure neuroinflammation and better understand the underlying activation pathways?
• How do we best understand the role of specific targets with regard to expression timeline at different stages of disease and activity level and in neuroinflammatory pathways?
• How can we create a physiologically relevant model that actually provides predictive results for clinical trials?
• What critical translational questions do we need to unravel to truly develop effective drugs targeting neuroinflammation?

9:30 am Identifying the Right Biomarkers to Track Neuroinflammation

Synopsis

• Developing biomarkers to fast track drug development targeting neuroinflammation, exploring various biomarker strategies
• What are the key targets that can help monitor neuroinflammation in the cns?
• Shall we aim to define a specific signature of neuroinflammation that would help define the state of disease and understand treatment response?
• Exploring senescence-induced inflammation: Is this an important player in drug development? Discovering the interplay between immunosenescence and age-related diseases
• Can we utilize markers of senescence to monitor inflammation?

10:20 am Networking Break

11:20 am Developing Remyelination Therapies for Neurodegenerative Diseases

  • Carlos Pedraza Associate Director Neuroimmunology & MS Therapeutics, Sanofi

Synopsis

• Myelin degeneration and/or dysregulation is a common characteristic of neurodegenerative and neuropsychiatric diseases
• Remyelination and neuroprotection therapies are the next frontier in drug development for neuroimmune and neurodegenerative pathologies
• How can we develop novel methodologies and medications to promote remyelination and repair of the affected nerve cells?
• How can we best translate this into clinical trials?
• Exploring our biomarker strategies for clinical development of remyelination therapies

11:45 am Genetic Ablation of Mouse Gpnmb Does Not Alter SynucleinRelated Pathology

  • Brad Friedman Senior Scientist, Department of OMNI Bioinformatics, Genentech

Synopsis

• Gpnmb is a transmembrane secreted protein that is expressed by activated myeloid cells in mouse and human
• Human genetics suggests that Gpnmb inhibition might provide therapeutic benefit for Parkinson’s disease
• Therefore, we characterized Gpnmb-KO mice in three different models of neurological disease, including two alpha-synuclein-driven models.
• Although all three models exhibited robust behavioral, neurochemical, histological, cellular and gene expression phenotypes, none of these was altered in Gpnmb-KO animals
• Therefore, these models are not suitable for studying the role of Gpnmb in development or progression of Parkinson’s disease

12:10 pm Role of C9orf72 in Inflammation & Neurodegeneration

  • Robert Baloh VP, Global Head of Research in Neuroscience & Rare Diseases, pRED at Roche

Synopsis

• Repeat expansions in C9orf72 are the major genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia
• Loss of function of C9orf72 in dendritic cells drives an autoinflammatory state that includes STING activation of type I IFN signaling
• Microglia lacking C9orf72 have an altered response to aging and amyloid plaque accumulation
• Endolysosomal regulation by the C9orf72/SMCR8 complex in myeloid cells has potential relevance to neurodegeneration, inflammatory diseases and cancer

12:35 pm Live Speaker Q&A

  • Carlos Pedraza Associate Director Neuroimmunology & MS Therapeutics, Sanofi
  • Brad Friedman Senior Scientist, Department of OMNI Bioinformatics, Genentech
  • Robert Baloh VP, Global Head of Research in Neuroscience & Rare Diseases, pRED at Roche

12:50 pm Networking Lunch

1:50 pm Targeting the Peripheral Nervous System

Synopsis

• What is the role of peripheral immune cells in the brain and to what extent to we understand peripheral-central neuroimmune crosstalk?
• What are our advances in peripheral inflammatory markers and clinical correlations?
• Exploring our philosophy – It’s not a solo performance, it’s a symphony
• How best to modulate Tcell function for neuroprotection (e.g. mechanistic work to elucidate various pathway overlaps including antigens, 2nd messengers, STING and the inflammasome work in the peripheral system)?
• Approaches we use to stratifying patients quantitatively with different forms of disease based on immune function and cell phenotypes

2:15 pm Untapping Astrocytes as a Source of New Targets for Neurodegenerative Disorders

  • Shane Liddelow Assistant Professor, Neuroscience Institute , NYU Langone

Synopsis

  • Why are astrocytes such a hugely overlooked cell population?
  • Elucidating the role of astrocytes in influencing the inflammatory response
  • What have we uncovered about astrocytes biology and the cross talk between the different cell type?
  • What are we missing to push forward new discoveries in astrocyte biology – particularly in relation to neurodegenerative diseases?

2:40 pm Live Speaker Q&A

2:55 pm Afternoon Break

Targeting the Inflammasomes & Their Role in Innate Immune & Inflammatory Responses

3:20 pm Targeting Inflammasomes for the Treatment of Inflammatory Diseases – Potential for CNS Disorders?

  • Rebecca Coll Principal Investigator, Lecturer in Immunobiology, Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, UK

Synopsis

• Overview of inflammasome signalling pathways.
• Overview of inflammasomes in relation to CNS disorders.
• Discussion of currently available inflammasome inhibitors and the development of these to target neurological diseases.
• Discussion of mechanisms of activation and potential targets in the inflammasome pathway in CNS disorders.
• Discussion of the therapeutic implications of targeting inflammasomes in CNS disorders.

3:45 pm Exploring the NLRP3 Inflammasome in Neurodegenerative Diseases

Synopsis

• Dissecting neuroimmune connections in aging and neurodegenerative diseases
• Driving our understanding of molecular mechanisms of inflammatory regulation
• Identification of new therapeutic approaches for neurodegenerative disease

4:10 pm GPCR19 Regulates P2X7R-mediated NLRP3 Inflammasomal Activation of Microglia by Amyloid β in Alzheimer’s Diseases

  • SY Seong Chief Executive Officer, Shaperon ; Professor, Department of Microbiology & Immunology, Seoul National University College of Medicine

Synopsis

• A GPCR19 agonist improved memory and cognition of 5xFAD mice
• Targeting GPCR19 and P2X7 ion channel therby regulate NLRP3 inflammasome activation
• Reducing neuroinflammation by decreasing Aβ plaques, number of activated microglia, ROS production and also by preventing neuronal apoptosiss in the brain of 5XFAD mice
• GPCR19 might provide clinical benefits by inhibiting redundant inflammasome pathways downstream of polymorphic P2X7

4:35 pm Exploring Inflammasome Activation After Traumatic Brain Injury

Synopsis

• The inflammasome contributes to the innate immune response after traumatic brain injury.
• Traumatic brain injury induces a systemic inflammatory response that is in part mediated by the inflammasome.
• IC100 inhibits inflammasome activation after traumatic brain injury.
• Inflammasome proteins are reliable biomarkers of traumatic brain injury.

5:00 pm Live Speaker Q&A

  • Rebecca Coll Principal Investigator, Lecturer in Immunobiology, Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, UK
  • SY Seong Chief Executive Officer, Shaperon ; Professor, Department of Microbiology & Immunology, Seoul National University College of Medicine
  • Juan Pablo De Rivero Vaccari Research Assistant Professor , University of Miami Miller School of Medicine
  • Michael Heneka Professor, University of Bonn Medical Centre

5:30 pm Chair’s Closing Remarks

End of Neuroimmunology Drug Development Summit