April 17-18, 2019
Boston, USA

 

 

 

 

Day One
Wednesday, April 17

Day Two
Thursday, April 18

08:30
Chair’s Opening Remarks

Validating Neuroinflammatory Targets

08:45
Beyond GWAS & Mouse Transcriptomes: Identifying Causal Alleles in Alzheimer’s Risk Loci & Understanding Differences Between Human & Mouse Microglia

Synopsis

  • Most GWAS-identified loci have unknown reasons for disease association
  • Discussing how a PILRA coding variant likely accounts for the association of the ZCWPW1 locus with Alzheimer’s risk
  • Acknowledging that certain aspects of human microglial activation are not captured in mouse neurodegeneration models

09:15
TREM2 Controls Microglial Lipid Metabolism Upon Chronic Phagocytic Challenge

Synopsis

  • Reviewing the gene expression studies showing that TREM2 KO microglia fail to reach the DAM state in a chronic demyelination paradigm
  • Studying lipidomic studies which show that TREM2 KO microglia accumulate lipids
  • Exploring the features shared by TREM2 KO microglia and aged microglia

09:45
Preclinical Validation of DLK Inhibition for Treatment of Alzheimer’s Disease Using RNA-seq in Mouse Models

  • Mary Hamby Head of Neuroinflammation Drug Discovery, The Neurodegeneration Consortium, MD Anderson

Synopsis

• Understanding the role of inappropriately activated DLK in neurodegenerative disorders
• Analyzing, through longitudinal RNAseq profiling, the role of DLK in two mouse models of Alzheimer’s disease
• Linking the role of DLK in Alzheimer’s disease to the previously identified dysregulation of an immune/microglia network in post-mortem human brain
• Shedding light on how inhibition of neuronal DLK confers benefit, at least in part, through alteration of the microglial phenotype

10:15
Morning Refreshments & Networking

Evaluating Therapeutic Approaches Targeting Neuroinflammation

10:45
Validating Target Engagement to Identify Appropriate Doses of Neuroinflammation-Targeted Therapeutics

Synopsis

  • Assessing methods for target engagement identification
  • Reviewing a case study of novel, potent and selective TLR2 antagonists which have been identified and further optimized
  • Target engagement blocks pro-inflammatory cytokine release in central and peripheral immune cells
  • Pre-clinical evaluation using multiple models of central and peripheral in vivo inflammation

11:15
Accounting for Disease Progression: When to Intervene

Synopsis

  • Evaluating the features of Alzheimer’s disease, an amyloid-mediated tauopathy?
  • Where does innate immunity fit into the AD cascade?
  • Discussing a potential stage-dependent role of microglia as suggested by preclinical data

11:45
Targeting & Isolating Neuroinflammatory Mechanisms: The Good, The Bad & Avoiding Comorbidity

Synopsis

  • Summarizing neuroinflammatory triggers and the cascade
  • Evaluating targets, ligands and their non-neuroinflammatory effects
  • Discussing how to identify the optimal target

12:15
Lunch & Networking

Neuroimmunology Biology & Pathology to Guide Future Drug Development

13:15
Identification of Novel Microglia Subsets & Their Differential Cellular Functions & Response to Aging & Neuroinflammation

  • Michael Mingueneau Senior Scientist, Multiple Sclerosis & NeuroInflammation Research, Biogen

Synopsis

  • Determining microglial states, subsets and functions in health and disease
  • Understanding how microglia play a key role in brain homeostasis and being able to preserve those functions while effectively blocking microglia pathogenic contributions in disease state will be crucial
  •  Identifying and characterizing microglia heterogeneity and subsets to aid the development of effective and safe drugs modulating microglia biology

13:45
Developing Monoclonal Antibodies to Target Microglial Functions in Neurodegeneration

Synopsis

  • Using human genetics to identify neuroinflammatory targets
  • Developing antibodies e.g. TREM2 agonist
  • Characterization of the antibodies in a variety of mouse models

14:15
A Novel Imaging-based Platform Points to Neuroprotective Microglia in Alzheimer’s models

Synopsis

  • Exploring target identification using GWAS and transcriptomic studies
  • Understanding the underlying mechanisms that mediate neuroimmune responses and modulate neuritic dystrophy across the disease course
  • Investigating disease stage-dependent functions of the microglia-plaque niche
  • Utilizing high-resolution confocal microscopy and a custom quantitative, semiautomated image analysis platform to generate a protective-barrier-index (PBI) for individual plaques

14:45
Mastermind: Service Provider Satisfaction & Opinions to Guide Future Partnerships

  • Mary Hamby Head of Neuroinflammation Drug Discovery, The Neurodegeneration Consortium, MD Anderson

Synopsis

As the field is still in its infancy, this discussion will focus on selection criteria and enable you to share experiences with your peers on vendor services to improve and accelerate neuroinflammation research.

  • What does the current service provider landscape look like in the neuroinflammation space?
  • Reviewing past success and lessons learned
  • What work is currently done in-house which you would prefer to use a third-party company?
  • What considerations are important to address when selecting service providers?

Use this session to assess failed and successful service provider relationships and how to to navigate significant challenges associated with working with third parties to direct future interest and research.

15:15
Afternoon Networking & Refreshments

The Blood-Brain-Cerebrospinal Fluid Barriers & Neuroinflammation

15:45
The [Re-]Emerging Role of Neurovascular Inflammation in Alzheimer’s Disease

  • Robert Nelson Co-founder & Vice President, MindImmune Therapeutics

Synopsis

  • What is old is new again: Understanding how new research complements older studies in implicating the peripheral immune system in AD pathology
  • This talk presents evidence that an innate immune cell termed the dendritic cell is recruited from blood to brain in both amyloid-depositing and neurofibrillary tangle-forming transgenic mouse models
  • Discuss the development of a platform approach identifying inhibitors of dendritic cell recruitment in AD, as well as a strategy for developing a near-infrared imaging biomarker of recruited dendritic cells in AD brain

16:15
Bypassing the Blood-Brain Barrier Via Intrathecal Delivery of Therapeutics: Mechanisms & Neuroimmunology Connections

  • Ajay Verma Senior Scientific Advisor, United Neuroscience & Annexon Biosciences

Synopsis

  • Underlying biological principles for delivering therapeutic molecules to the central nervous system through intrathecal dosing
  • Assessing the impact of neuroanatomy, dosing parameters, therapeutic modality, CSF-CNS molecular exchange mechanisms and CSF clearance routes
  • Elucidation of inter-thecal CNS immune surveillance networks relevant to disease and therapeutics

16:45
Panel Discussion: Exploring Technologies to Effectively Transport Large Molecules Across the BBB

  • Robert Nelson Co-founder & Vice President, MindImmune Therapeutics
  • Ajay Verma Senior Scientific Advisor, United Neuroscience & Annexon Biosciences
  • Yaming Wang Senior Research Scientist, Eli Lilly

Synopsis

  • What are the biggest challenges for targeting the CNS?
  • What current methods are available for allowing drug delivery to the CNS?
  • Debating the disadvantages and advantages of various technologies
  • Guiding future development for crossing the blood-brain barrier

17:15
Chair’s Closing Remarks