Aigner intelgenx

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© Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner Rejuvenation of the Aged Brain An Example of Drug Delivery in Drug Repurposing Ludwig Aigner IntelGenx, Grand Opening, Saint-Laurent, May 10th 2016

Transcript of Aigner intelgenx

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© Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner

Rejuvenation of the Aged Brain

An Example of Drug Delivery in Drug Repurposing

Ludwig Aigner

IntelGenx, Grand Opening, Saint-Laurent, May 10th 2016

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YESTERDAY

© Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 2

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TODAY

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TOMORROW

© Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 4

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Age: Risk Factor Number 1

Teresa Niccoli , Linda Partridge, Ageing as a Risk Factor for Disease, Current Biology, Volume 22, Issue 17, 2012, R741 - R752

© Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner

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Massive Increase in the Prevalence of AD

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GeneticNon-Genetic

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Alt

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Alzheimer Pathology

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Are We Targeting the Right Thing ?

Rodrigue et al., Neuropsychol Rev. 2009

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1001 Reasons for Neuronal Cell Death ???

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Neurodegenerationeg Schapira et al. 2011

Neuroinflammationeg Hirsch et al. 2009

Blood Brain Barriereg Zlokovic et al. 2008

Neurogenesiseg Regensburger et al. 2014

Neurotransmissioneg Calabresi et al. 2007

Our Targets:

Pleiotropic Signaling

Demyelination

Axonal Damage

eg Franklin et al. 2008

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AGING and REJUVENATION

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Neurodegenerationeg Schapira et al. 2011

Neuroinflammationeg Hirsch et al. 2009

Blood Brain Barriereg Zlokovic et al. 2008

Neurogenesiseg Regensburger et al. 2014

Neurotransmissioneg Calabresi et al. 2007

Demyelination

Axonal Damage

eg Franklin et al. 2008

The Aged Brain is a „Diseased“ Brain

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Regeneration

Disease RiskDisease Risk

Live = Aging

Growth Plasticity Degeneration Disease

© Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 18

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Growth Plasticity Degeneration

Aging and Rejuvenation

„Regenerative Pharmacology“

Disease

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Can We Turn Back the Clock ?

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Muscle Research, Aging, and Regenerative Medicine ?

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inflammation

neurogenesis

cognitiion

Modulating the Systemic Milieu: a Valid Approach

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Eotaxin Reduces Neurogenesis

Eotaxin Worsens Cognition

Old Blood Contributes to Brain Aging

EOTAXIN

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Eotaxin Leukotrienes

Allergy / Asthma Brain Aging

Aging / Degeneration

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Leukotrienes Impact on Brain Aging

Leukotrienes

Neurodegenerationeg Schapira et al. 2011

Neuroinflammationeg Hirsch et al. 2009

Blood Brain Barriereg Zlokovic et al. 2008

Neurogenesiseg Regensburger et al. 2014

Neurotransmissioneg Calabresi et al. 2007

Demyelination

Axonal Damage

eg Franklin et al. 2008

Monte

lukast

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Proof of Principle:

Inhibition of Leukotriene Receptors Improves Cognition in Aged Rats

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symptoms pathology therapy

motoric dopaminergic cell loss dopamine replacement

60%

Parkinson´s Disease Dementia / Lewy Body Dementia

symptoms pathology therapy

motoric dopaminergic cell loss dopamine replacement

dementia ??? rivastigmine

Neurogenesis

Blood Brain Barrier

Neuroinflammation

Neurodegeneration

Neurotransmission

eg Schapira et al. 2011

eg Hirsch et al. 2009

eg Zlokovic et al. 2008

eg Regensburger et al. 2014

eg Calabresi et al. 2007

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**

Learning Memory

*

Montelukast Improves Cognitive Functions in PD / LBD Animals

© Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 30

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sAnnual Counts of Publications “Drug Repurposing”

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“All De- and Regenerations are Similar”

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REPAIR

REPLACE

RESTORE

REGENERATE

REJUVENATE

Regenerative Medicine

All Organs

Different Diseases

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MMSE 13: moderate to severe dementia

Montelukast as an Anti-Dementia Therapeutic

Before After 2 Months of Montelukast

MMSE 22: mild dementia

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Discover

y

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Phase

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Approval

BIOTECH

Academia Big Pharma

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Let‘s make a better Montelukast