|Date||Theme, lectures and discussants||Participants|
|Epidemiology and pathology|
|Introduction||Patrick Vanderdonckt (Kortrijk, Belgium) & Giancarlo Comi (Milan, Italy)|
|Lecture 1||Causation theory and how it applies to EBV as a cause of MS
What more needs to be done to prove EBV is the cause of MS? What is the definitive experiment then?
|Alberto Ascherio (Cambridge; USA)|
|The epidemiology of MS and EBV
How does EBV explain the epidemiology of MS, i.e. increasing incidence, increasing female:male sex ratio,altitudinal gradient, etc.?
Potential mechanisms of how EBV interacts with other environmental risk factors to cause MS?
What further studies are required to establish how EBV interacts with other risk factors?
|Ingrid Kockum (Stockholm, Sweden)|
|The genetics of MS and how they interact with EBV
How does EBV interact with the MS-transcriptome?
What needs to be done to explore the genomics of EBV and MS?
|Phil De Jager (New York, USA)|
|Invited discussant - EBV and MS||Marco Salvetti (Rome, Italy)|
|Q&A / Discussion at the end of day 1||Giancarlo Comi (Milan, Italy) & Gavin Giovannoni (London, UK)|
|Day 2.1 6-July-2022||Pathology and the immunopathology of MS|
|EBV and the pathology of MS and related disorders
What is MS in relation to other inflammatory demyelinating diseases?
What is the key mechanism, which drives chronic (progressive) pathology; is this the aspect which differentiates MS from other acute monophasic or relapsing inflammatory demyelination diseases (such as MOGAD)?
|Hans Lassmann (Vienna, Austria)|
|EBV as a driver of MS disease activity
What is the evidence against the hit-and-run hypothesis? In which compartment is EBV driving MS disease activity?
Regarding detection of EBV in brain tissue; is it pathogenic, a bystander phenomenon or an artefact?
|Francesca Aloisi (Rome, Italy)|
|EBV and MRI
Does MRI activity correlate with EBV biology?
How do you explain end-organ damage markers in relation to EBV?
|Robert Zivadinov (Buffalo, USA)|
|Day 2.2 6-July-2022||Animal models of EBV infection and MS|
|How good are humanised mice at representing EBV infection in relation to MS
How good are humanised mice at recapitulating human immunology?
Can mice be used to define the role of the MHC in MS?
Can human mice be used to develop and test new MS treatments?
|Christian Münz (Zürich, Switzerland)|
|What can we learn from rabbit model of EBV
What can we learn about a spontaneous CNS infection model of EBV?
What is the relevance of primary CNS infection with EBV to MS?
Can this animal model be used to develop treatment for MS?
|Gulfaraz Khan (Al Ain, UAE)|
|Is Japanese macaque encephalomyelitis (JME) animal MS?
How closely does the pathology and imaging features of JME mimic MS?
What are the differences between CIS and acute JME and MS?
Does JME responde to MS DMTs?
|Dennis Bourdette (Portland, Oregon)|
|Q&A / Discussion at the end of day 2||Hans Lassmann (Vienna, Austria) & Gavin Giovannoni (London, UK)|
|Day 3 - 7-July-2022||Immunopathology of MS|
|EBNA-1 and MS
What is the biology of EBNA-1 and how does its biology differ in people with MS?
How to target EBNA-1 as a potential target to treat MS?
|Lawrence Young (Warwick, UK)|
|EBNA2 and the B-cell
EBNA-2 and its effect on B-cell biology
How is this relevant to MS and autoimmunity in general?
|Matt Weirauch (Cincinnati, USA)|
|Molecular mimicry, EBV and MS
What is the case for EBV molecular mimicry in the pathogenesis of MS?
What is the MS autoantigen?
Targeting molecular mimicry as a treatment option in MS?
|Ivan Jelcic (Basel, Switzerland)|
|T-cell therapy and related issues
What lessons can be learnt from infectious mononucleosis
Can we use EBV-specific T-cell therapies to treat MS?
|Rajiv Khanna (Brisbane, Australia)|
|The immunology of MS and how it interacts with EBV
Can latent EBV infection of B-cells explain the aberrant B-cell biology in MS?
What further experiments need to be done to test the EBV-B-cell hypothesis?
|Jan Lünemann (Münster, Germany)|
|Memory B-cells and MS
What is the evidence that the memory B-cell is the primary driver of MS disease activity?
Could this be explained by latent EBV infection?
|Joseph Berger (Philadelphia, USA)|
|EBV and the MS B-cell repertoire
Is EBV involved in the generation of the oligoclonal IgG response?
What have we learnt about the immunoglobulin repertoire in MS?
What needs to be done to further explore the link between EBV and the intrathecal oligoclonal IgG?
|William Robinson (Stanford, USA)|
|Q&A / Discussion at the end of day 3||Hans-Peter Hartung (Dusseldorf, Germany) & Gavin Giovannoni (London, UK)|
|Day 4 - 8-July-2022||The viral hypothesis of MS|
|The dual viral hypothesis of MS
Is EBV working via human endogenous retroviruses?
What about the negative association between HIV and MS; is due to HERVs?
|Zsolt Illes (Odense, Denmark)|
|Treating MS with antivirals
What is the evidence that antivirals work in MS?
What trials are needed to test the viral hypothesis of MS?
|Julian Gold (Sydney, Australia)|
|EBV the virus
The genetic evolution of EBV
Can diversity in the EBV genome potentially explain the EBV-MS association?
What hypotheses need testing and what experiments need to be done?
|Judith Breuer (London, UK)|
|Infectious mononucleosis and MS
The changing epidemiology of IM
How can we target IM as a possible preventive strategy for MS?
|Henry Balfour (Minnesota, USA)|
|How to design an EBV vaccine experiment to prove EBV causes MS
Does the EBV vaccine need to result in sterilising immunity?
How long does the trial have to be?
Can you design a shorter experiment?
What happens if the EBV vaccine trial doesn't work?
|Gavin Giovannoni (London, UK)|
EBV vaccine update
How far are we from MS prevention studies?
|Jeff Cohen (NIH Bethesda, USA)|
|Power calculations for EBV vaccine prevention studies
How big do the studies need to be?
What is the target population?
Can we use an intermediate phenotype as a primary outcome measure?
|Gary Cutter (Birmingham, Alabama; USA)|
|Administrative health records as a tool to explore the EBV-MS hypothesis
What can be done with administrative health records to explore the MS EBV hypothesis?
What resources are required to do this work?
|Ruth Ann-Marrie (Manitoba, Canada)|
|Q&A / Discussion at the end of day 4||Gavin Giovannoni (London, UK) & Hans-Peter Hartung (Dusseldorf, Germany)|
|Open discussion and conclusions and next steps||Gavin Giovannoni, Hans Lassman, Giancarlo Comi & Patrick Vanderdonckt|
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