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Neurodegenerative Disorders
30 June - 1 July 2004
Neurodegenerative Disorders
This event comes at a crucial time, when there is a huge demand for new drug candidates to be developed and to go through trials. The Conference will look at some of these novel candidates in Phase II and III. It will also take a look at how neurodegeneration can be monitored and assessed and the problems encountered in clinical trials. It will examine how therapeutic strategies, delivery solutions and individualised treatments may increase our chances of helping the vast numbers of patients with neurodegenerative conditions.

A unique opportunity to hear from leading experts including:
· Dr Menelas Pangalos, Vice President, Neuroscience Research, Wyeth
· Dr Michael J O’Niell, Team & Project Leader, Discovery Neuroscience, Eli Lilly
· Prof David Brooks, Chief Medical Officer, Imanet, Amersham Health
· Dr Robert Brashear, Director, CNS, Johnson & Johnson
· Dr Laurent Pradier, Director, Target Validation, CNS/AlzheimerAventis
· Dr Colin Dingwall, Senior Team Leader, GlaxoSAE Media GroupthKline
· Dr Charlotte Videbaek, Manager, Integrated HealthCare, F Hoffmann-La Roche
· Dr Johann Karl, Director, New Reagents, Roche Diagnostics
· Dr Bastian Hengerer, Group Leader, CNS Research II, Boehringer-Ingelheim
· Dr Dirk Beher, Research Fellow, Merck Sharp & Dohme

Programme highlights include:
· DISEASE-MODIFYING STRATEGIES: Learn how gamma secretases, AMPA receptor potentiators, the BASE 1 enzyme and JNKs are being targeted
· ANIMAL MODELS: Hear about the latest advances in APP and presenilin transgenic models for AD, together with murine models for motorneuron and Purkinje cell degeneration
· BIOMARKERS: Investigate the different approaches used to overcome the complex issues in diagnosis and monitoring of neurodegenerative disorders
· IMAGING: Gain an insight into the use of MRI, PET and SPECT imaging in AD and PD
· CLINICAL TRIALS: Discover how to overcome the problems encountered during clinical trials including patient recruitment and retention

Conference agenda

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8:30

Registration and Coffee

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9:00

Neuroprotective therapies

  • Lessons from stroke and traumatic brain injury
  • Issues for chronic neurodegenerative disorders
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    10:00

    The pivotal role of DMPK in CNS drug discovery

  • Drug metabolism
  • Pharmacokinetics
  • Neuropharmacokinetics
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    11:00

    Morning Coffee

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    11:15

    What is the best screening strategy to identify disease-modifying drugs for chronic neurodegenerative disorders?

  • In silico tools – are they predictive?
  • In vitro studies – are they reliable?
  • In vivo studies – do they predict what happens in humans?
  • Clinical DMPK and the optimal dosing regimen
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    12:10

    Discussion and questions – review of the session

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    12:30

    Close of Executive Briefing

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    13:30

    Registration and Coffee

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    14:00

    Use of cognitive function as a surrogate marker

  • Illustrations from recent studies where cognitive function have added to the strength of the signal
  • Designing trials to assess cognitive function
  • The NIMH/FDA initiative for cognitive function as a possible indication for schizophrenia – case history
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    14:30

    Startle response

  • Translational research – from animal models to man
  • How can one use prepulse inhibition of the startle response as a surrogate marker of efficacy in schizophrenia?
  • Using fear-modulated startle as a surrogate marker for efficacy in anxiety
  • Modulating the startle response with mood changes – insights into development of the drugs in depression
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    15:45

    Evoked potential, critical flicker fusion and eye movements as surrogate markers

  • How do these markers add value to drug discovery?
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    16:30

    Demonstration of the Cogtest software

  • How can one make an intelligent choice of a cognition CRO?
  • New developments in computerised cognition testing - electronic data capture, tests of verbal ability, social cognition and web reporting
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    17:15

    Discussion and questions – review of the session

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    17:30

    Close of Executive Briefing

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    8:30

    Registration and Coffee

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    9:00

    Chairperson's Opening Remarks

    Dr Adele Rowley

    Dr Adele Rowley, Director, Pharmacology & Head, Alzheimer’s Disease Area, Cellzome

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    9:10

    21ST CENTURY THERAPEUTICS FOR THE TREATMENT OF ALZHEIMER'S DISEASE

    Dr Menelas Pangalos

    Dr Menelas Pangalos, Vice President, Neuroscience Research, Wyeth

  • Drug discovery strategies for neurodegeneration and Alzheimer’s disease research
  • Approaches to improved symptomatic therapies
  • Approaches to disease-modifying therapies
  • Approaches to disease-reversing therapies
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    9:40

    INTRODUCTION TO PARKINSON’S DISEASE

    Dr Bastian Hengerer

    Dr Bastian Hengerer, Group Leader, CNS Research II, Boehringer-Ingelheim

  • Pathophysiology of PD
  • Concepts for disease-modifying treatments
  • Concepts for symptomatic treatments
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    10:20

    BACE1 BIOLOGY AND THE SEARCH FOR INHIBITORS AS THERAPEUTICS IN ALZHEIMER’S DISEASE

    Dr Colin Dingwall

    Dr Colin Dingwall, Senior Team Leader, GlaxoSmithKline

  • BACE1 is the key enzyme in the generation of amyloid in the AD brain
  • Approaches to the identification of potent and selective inhibitors
  • Amyloid production is sensitive to cellular cholesterol levels
  • The link between cholesterol levels and BACE1 activity
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    11:00

    Morning Coffee

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    11:30

    PROTEASE INHIBITION AS POTENTIAL DISEASE-MODIFYING STRATEGY FOR AD

    Dr Dirk Beher

    Dr Dirk Beher, Research Fellow, Merck Sharp & Dohme

  • Overview of gamma-secretase and intramembranous proteolysis
  • Structural diversity of gamma-secretase inhibitors
  • General issues associated with gamma-secretase inhibition
  • NSAIDs and gamma-secretase modulation
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    12:10

    POTENTIATION OF NMDA RECEPTOR ACTIVITY AS A NEW APPROACH FOR THE TREATMENT OF COGNITIVE DISORDERS AND SCHIZOPHRENIA

    Donna Oksenberg

    Donna Oksenberg, Director of Pharmacology and Biology, AGY Therapeutics

  • NMDA receptor dysfunction in cognition and schizophrenia
  • Role of tyrosine phosphorylation in NMDA receptor function
  • Intracellular tyrosine phosphatases modulate NMDA receptor signalling
  • Inhibition of tyrosine phosphatases potentiates NMDA receptor signalling
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    12:50

    Networking Lunch

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    13:50

    AMPA RECEPTOR POTENTIATORS AND PD

    Dr Michael O’Neill

    Dr Michael O’Neill, Team & Project Leader, Discovery Neuroscience,, Eli Lilly

  • Overview of models used to test disease-modifying drugs
  • Screening to discover AMPA potentiators
  • Effects of endogenous signalling pathways
  • Functional, neurochemical and histopathological effects
  • Neurotrophic actions of AMPA potentiators in PD models
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    14:30

    ANIMAL MODELS FOR NEURODEGENERATION

    Dr Klaus Dembowsky

    Dr Klaus Dembowsky, Vice President, Drug Discovery, Ingenium Pharmaceuticals

  • Drug discovery for neurodegeneration is hampered by the lack of respective animal models
  • Large scale forward and reverse genetics by random mutagenesis in mice is an established, highly efficient and fast technology for discovery of novel pathways, target validation and generation of respective disease models
  • Murine models of motorneuron and Purkinje cell degeneration have been identified by the forward genetic approach and will be described - Cra-1 and Granny
  • The reverse genetic approach uses a sperm archive from more than 10,000 mice after random mutagenesis and enables the identification of an average of 7 independent alleles for any gene and the generation of the respective mouse models in a few weeks
  • This reverse genetic approach with random mutagenesis is currently also applied to rats with the aim to generate disease models for therapeutic areas in which the rat is the species of first choice for drug testing and pathway analysis, eg neurodegeneration
  • The technique and first results in the rat
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    15:10

    Afternoon Tea

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    15:15

    Afternoon Tea

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    15:30

    NEW MODELS IN ALZHEIMER'S DISEASE

    Dr Laurent Pradier

    Dr Laurent Pradier, Director, Target Validation, CNS/Alzheimer, Aventis

  • Current transgenic models of amyloidosis
  • Early markers of pathology and neuronal dysfunction
  • Beyond amyloidosis, characterising neuronal loss in novel models
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    16:10

    IMPROVING DIAGNOSIS AND TREATMENT MONITORING BY USE OF BIOMARKERS IN NEURODEGENERATIVE DISEASE

    Dr Charlotte Videbaek

    Dr Charlotte Videbaek, Manager, Integrated HealthCare, F Hoffmann-La Roche

  • The changing need for biomarkers in neurodegenerative diseases: - Preclinical research tool, diagnostic tool, personalised medicine, treatment monitoring
  • Use of genetics as biomarker in neurodegeneration
  • Search for biochemical biomarkers - Biomarkers in the cerebrospinal fluid - Peripheral biomarkers
  • What is the role of neuroimaging as biomarker in neurodegenerative disorders?
  • Future perspective
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    16:50

    PREDICTABILITY OF RODENT MODELS FOR IN VIVO STUDIES

    Dr Kadar Thiam

    Dr Kadar Thiam, Senior Scientific Consultant, Director of Transgenic Technologies, GenOway

  • Limits and characteristics of genetically engineered animals
  • Target validation & lead optimisation: use of RNAi in transgenic mouse & in vivo conditionnal knock-out approach
  • In vivo screening using humanised models: "Quick Knock- in TM" & conditional humanisation approaches
  • In vivo studies of metabolic pathways: gene function evaluation & epigenetic regulation
  • Gene targeting in rat
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    17:30

    Chairperson’s Closing Remarks and Close of Day One

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    8:30

    Re-registration and Coffee

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    9:00

    Chairperson's Opening Remarks

    Prof Leslie Iversen

    Prof Leslie Iversen, Director, Wolfson Centre for Age Related Diseases, King’s College London

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    9:10

    BIOMARKERS IN ALZHEIMER'S DISEASE AND ITS POTENTIAL USE IN DRUG DEVELOPMENT

    Dr Eugeen Vanmechelen

    Dr Eugeen Vanmechelen, Senior Manager, Neurodegeneration Research & Development, Innogenetics

  • Few biochemical markers have been evaluated in pathologically confirmed cases and for early diagnosis - tau/phospho-tau and amyloid42 in cerebrospinal fluid as example
  • A multiparameter approach is needed for high clinical performance
  • Proteomic approaches to finding relevant markers for AD in blood
  • Observations on changes of tau/phospho-tau and amyloid42 in treated AD patients
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    9:40

    PATIENTS RECRUITMENT AND LOGISTICS IN NEURODEGENERATIVE DISORDERS CLINICAL TRIALS

  • · Logistic aspects during the project start up phase
    · Investigational sites selection, centres of excellence
    · Effects of protocol and CRF design
    · Use of scales, inter-rater reliability training and certification
    · Future perspective
  • Patients recruitment strategies in neurodegenerative disorders clinical trials
    · Key factors influencing patient recruitment
    · Patient retention in long-term clinical trials
    · Investigational sites and networks in patient recruitment
    · Future perspective
  • Dr Agnes Domonique-Mesnage

    Dr Agnes Domonique-Mesnage, Senior Director, Medical Solutions , Quintiles Europe

    Dr János Filakovszky

    Dr János Filakovszky, Head, Medical Solutions, Quintiles Europe

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    10:20

    NICOTINIC ACETYLCHOLINE RECEPTOR CHANGES IN PD AND AD

    Dr Jenny Court

    Dr Jenny Court, Manager, Brain Bank / Honorary Lecturer, Institute of Ageing / Newcastle University

  • Distribution of nAChR subtypes in human brain
  • nAChR deficits in AD and PD
  • Correlation of nAChR deficits with changes in other neurochemical markers and neuropathological indices
  • Implications for therapy both symptomatic and neuroprotective
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    11:00

    Morning Coffee

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    11:30

    IMAGING IN ALZHEIMER’S

    Marie Luby

    Marie Luby, Director, CNS Program, Perceptive Informatics

  • Overview of MRI sequences
  • Review of past trial analyses
  • Future techniques and applications
  • Summary of technical considerations
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    12:10

    ADAPTING CLINICAL DEVELOPMENT METHODS TO CURRENT KNOWLEDGE

    Dr Christian Gilles

    Dr Christian Gilles, Director, Research & Development & Head, CNS Ageing Research, Forenap

  • Proof of concept for symptomatic treatment - the place of human models in phase I trials
  • Proof of concept for disease-modifying treatment - can healthy volunteer studies contribute?
  • Disease-modifying treatments - safety issues in phase I studies
  • The place of bridging studies
  • Is placebo still justified in patient studies?
  • Assessment of efficacy - which endpoints, which tools?
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    12:50

    Networking Lunch

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    14:10

    NICOTINIC MODULATION IN THE TREATMENT OF DEMENTIA

    Dr H Robert Brashear

    Dr H Robert Brashear, Director, CNS, Johnson & Johnson

  • Galanthamine as an acetylcholinesterase inhibitor and nicotinic modulator
  • Allosteric potentiating ligand effects on nicotinic receptors
  • Effects on neurotransmitter release
  • Effects on learning in animal models
  • Evidence from functional imaging
  • Evidence from clinical trials
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    14:50

    METALLO-PROTEIN ATTENUATION COMPOUNDS (MPACS) AND ALZHEIMER’S DISEASE

    Dr Craig Ritchie

    Dr Craig Ritchie, Lead Clinical Consultant / Clinical Director, Clinical Trials Unit, Prana Biotechnology / Royal Free Hospital, UCL

  • Overview of role of metals in AD pathology
  • Clinical trial program for PBT-1
  • Development program of PBT-2
  • Other therapeutic areas for MPAC technology
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    15:30

    Afternoon Tea

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    15:50

    ROLE OF IMAGING IN PARKINSON’S DISEASE

    Prof David Brooks

    Prof David Brooks, Chief Medical Officer, Imanet, Amersham Health

  • Monitoring PD progression and testing efficacy of neuroprotection
  • Measuring neuro-inflammation
  • Providing proof of concept for novel pharmaceuticals and defining dose-occupancy profiles
  • Measuring down stream effects of drugs
  • Determining protein aggregation load
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    16:30

    TEASING OUT SINGLE MECHANISMS OF ACTION OF SAFINAMIDE, AN ANTI-PARKINSON AGENT WITH NEUROPROTECTANT FEATURES

    Prof Ruggero Fariello

    Prof Ruggero Fariello, Chief Scientific Officer, Newron Pharmaceuticals

  • Neuroprotection, the new frontier
  • Safinamide - an anticonvulsant with dopamine metabolism regulating properties
  • Kinetic and dynamic studies to unravel a drug’s mechanism of action
  • How to tease out various mechanistic components of the clinical effects
  • Symptomatic versus disease-modifying therapy
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    17:10

    Chairperson's Closing Remarks followed by Afternoon Tea and Close of Conference

    Workshops

    DMPK in R&D for Neurodegenerative Disorders

    DMPK in R&D for Neurodegenerative Disorders

    The Hatton, at etc. venues
    2 July 2004
    London, United Kingdom

    The Hatton, at etc. venues

    51/53 Hatton Garden
    London EC1N 8HN
    United Kingdom

    The Hatton, at etc. venues

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    WHAT IS CPD?

    CPD stands for Continuing Professional Development’. It is essentially a philosophy, which maintains that in order to be effective, learning should be organised and structured. The most common definition is:

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