Conference Day Two

Thursday 23rd May, 2019

8.15          Chair’s Opening Remarks

Exploring Preclinical Models of Neurodegeneration to Improve Clinical Efficacy Predictions


Neurodegeneration: Novel Animal Models of Alzheimer’s Disease

  • Genetic animal models are diverse and serve various purposes
  • These models have translational value within the biochemical process that is
    impacted, but do not reflect the full human disease phenotype
  • Understanding that overexpression of mutated gene is often a confounding
  • Exploring new animal models hold promise for improved translational value

Luc Ver Donck
Scientific Director, Head of Alzheimer Disease Animal Models, Neuroscience Discovery


Molecular & Functional Characterisation of IPSC-Derived Microglia: Developing Tools to Model Neurodegeneration

  • Developing a scalable and reproducible generation of physiologically-relevant
  • Validation of robust, disease-relevant assays
  • Building a translatable neurodegeneration model: longitudinal monitoring of
    healthy and patient donor iPSC co-cultures
  • Assessing the contribution of astrocytes and microglia to the neuroinflammatory

Daniel Rock
Microglia Application Specialist
Axol Bioscience


Reverse Translation in Practice: Gaining More Valuable Information from Animals Models in Neurodegenerative Drug Discovery

  • Neurodegenerative drug discovery efforts have faced significant challenge from a recent series of late-stage failures. Promising preclinical data has not been recapitulated in the clinic
  • Animal models should be more carefully aligned with human disease characteristics and outcomes
  • Bridging the translational gap by greater use of physiological correlates to map drug effects on brain activity between humans and rodents
  • An overview of recent advances in strategies and concepts of reverse translation

Jo Jackson
Senior Research Scientist
Eli Lilly


Morning Refreshments & Networking

Assessing Current Methods of Validation of Neurodegenerative Targets


Epitope Determines Efficacy of Therapeutic Anti-Tau Antibodies in a Functional Assay with Human Alzheimer Tau

  • Growing evidence suggest that tau misfolds and may propagate pathology by spreading from cell to cell in a ‘prion like’ manner
  • Blocking the spread of extracellular seeds with an antibody may therefore be a viable therapeutic approach
  • We developed a robust and quantitative cell based assay and employed an unbiased screening approach to identify the antibody with the highest activity against human tau seeds isolated from AD and PSP patients
  • We found that an antibody targeting the mid-region of Tau was more efficacious
    than N-terminal antibodies in this assay and our data highlights the difficulty of predicting antibody accessible epitopes on pathological tau seeds

Patrick Downey
Director, Head of Neurodegeneration


The Need for Strategical Changes in Alzheimer’s Disease Research

  • Understanding the biology behind AD
  • Discussing the current biomarkers of neurodegeneration and future opportunities
  • Accounting for disease heterogeneity
  • Reviewing the lessons learned from the last decade

Angel Cedazo-Minguez
Head of Neuroscience Research

12.00 Lunch & Networking

Assessing Therapeutic Approaches Targeting Neurodegeneration


Gene therapy for a neurodegenerative lysosomal storage disease by direct to brain delivery of a recombinant AAV vector

  • Reviewing the challenges of gene therapy for CNS diseases
  • Assessing the delivery of AAV vectors to the CNS
  • Proving preclinical proof of concept using disease models
  • Evaluating the translation of gene therapy therapeutics to the clinic

Ralph Laufer
Chief Scientific Officer


Creating Healthy Dopaminergic Neurons by Novel Approaches to Parkin Modulators

  • Current treatments for Parkinson’s disease cannot prevent dopaminergic neuron destruction or treat the underlying causes of neurodegeneration
  • Human genetics and biochemical data indicate that dysfunction in the ubiquitin proteasome system is the cause of PD/AD and damaged mitochondria accumulate and contribute to neuronal death
  • The ubiquitin ligase Parkin eliminates damaged mitochondria and preserves neuronal health. Small molecule Parkin modulators could be developed into drugs that can treat PD
  • Identifying modulators of Parkin that restore damaged mitochondria and build new mitochondria
  • Presenting a pharmacological profile of these compounds, including their mechanism of action and effects on PD and AD models

Tauseef Butt
Chief Executive Officer

2.30 Afternoon Refreshments & Networking

Utilising Biomarker Strategies to Improve Patient Stratification for Clinical Trials


Identification of Biomarkers for Early Detection of Neurodegenerative Phenotypes: Application to Clinical Development

  • Highlighting the pre-symptomatic period of neurodegenerative diseases where  characteristic neuropathological changes are already detectable
  • Identifying individuals at an early stage of the disease with biomarkers of the underlying pathology (fluid, imaging, genetic, digital) when potential disease modifying therapies may have a better chance of success
  • Over the last decade such biomarkers were successfully developed in the field of Alzheimer’s Disease; they became integral part of AD research diagnostic criteria, and are commonly in use in clinical trials
  • Discussing the application of such approaches to clinical development in other neurodegenerative diseases

Gregory Klein

Principal Scientist


Improving Stratification in Neurodegenerative Disease Using Imaging & Other Endpoints

  • Identifying the right patient for the right drug, study or trial is vital, therefore improving our ability to accurately stratify in complex disorders is key
  • Introducing improved imaging agents and techniques which are offering fascinating insights into these disorders and hence improved stratification
  • Combining different modalities and other endpoints can further enhance this process as preliminary data from the IMI PRISM project will illustrate

Hugh Marston
Senior Research Fellow & Head of Translational Neuroscience
Eli Lilly


Panel Discussion: Optimising Clinical Studies: Valid Biomarkers & Patient Stratification

  • How best to identify the correct patient populations using early biomarkers of neurodegenerative disease
  • Strategies for patient recruitment
Richard Wyse Image

Richard Wyse
Global Director of Research and Development
The Cure Parkinson’s Trust

Hugh Marston Senior Research Fellow & Head of Translational Neuroscience Eli Lilly

Hugh Marston
Senior Research Fellow & Head of Translational Neuroscience
Eli Lilly

Untitled design (85)

Gregory Klein

Principal Scientist

4.30 Chair’s Closing Remarks