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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

  • YESTERDAY

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

  • TODAY

    © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 3

  • TOMORROW

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

  • 5

    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

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 6

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 7

    Massive Increase in the Prevalence of AD

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 8

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 9

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 10

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 11

    GeneticNon-Genetic

  • Alt

    © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 12

    Alzheimer Pathology

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 13

    Are We Targeting the Right Thing ?

    Rodrigue et al., Neuropsychol Rev. 2009

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 14

    1001 Reasons for Neuronal Cell Death ???

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 15

    Neurodegeneration eg Schapira et al. 2011

    Neuroinflammation eg Hirsch et al. 2009

    Blood Brain Barrier eg Zlokovic et al. 2008

    Neurogenesis eg Regensburger et al. 2014

    Neurotransmission eg Calabresi et al. 2007

    Our Targets:

    Pleiotropic Signaling

    Demyelination

    Axonal Damage

    eg Franklin et al. 2008

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 16

    AGING and REJUVENATION

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 17

    Neurodegeneration eg Schapira et al. 2011

    Neuroinflammation eg Hirsch et al. 2009

    Blood Brain Barrier eg Zlokovic et al. 2008

    Neurogenesis eg Regensburger et al. 2014

    Neurotransmission eg Calabresi et al. 2007

    Demyelination

    Axonal Damage

    eg Franklin et al. 2008

    The Aged Brain is a „Diseased“ Brain

  • Regeneration

    Disease Risk Disease Risk

    Live = Aging

    Growth Plasticity Degeneration Disease

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

  • Growth Plasticity Degeneration

    Aging and Rejuvenation

    „Regenerative Pharmacology“

    Disease

    © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 19

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 20

    Can We Turn Back the Clock ?

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 21

    Muscle Research, Aging, and Regenerative Medicine ?

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 22

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 23

    inflammation

    neurogenesis

    cognitiion

    Modulating the Systemic Milieu: a Valid Approach

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 24

    Eotaxin Reduces Neurogenesis

    Eotaxin Worsens Cognition

    Old Blood Contributes to Brain Aging

    EOTAXIN

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 25

    Eotaxin Leukotrienes

    Allergy / Asthma Brain Aging

    Aging / Degeneration

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 26

    Leukotrienes Impact on Brain Aging

    Leukotrienes

    Neurodegeneration eg Schapira et al. 2011

    Neuroinflammation eg Hirsch et al. 2009

    Blood Brain Barrier eg Zlokovic et al. 2008

    Neurogenesis eg Regensburger et al. 2014

    Neurotransmission eg Calabresi et al. 2007

    Demyelination

    Axonal Damage

    eg Franklin et al. 2008

    M o n te

    lu k a s t

  • Proof of Principle:

    Inhibition of Leukotriene Receptors Improves Cognition in Aged Rats

    © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 27

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 28

  • 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

    © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 29

  • **

    Learning Memory

    *

    Montelukast Improves Cognitive Functions in PD / LBD Animals

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

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 31

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 32

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    N u

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    s Annual Counts of Publications “Drug Repurposing”

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 33

    “All De- and Regenerations are Similar”

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 34

    REPAIR

    REPLACE

    RESTORE

    REGENERATE

    REJUVENATE

    Regenerative Medicine

    All Organs

    Different Diseases

  • © Paracelsus Medizinische Privatuniversität | Institute of Molecular Regenerative Medicine | Ludwig Aigner 35

    MMSE 13: moderate to severe dementia

    Montelukast as an Anti-Dementia Therapeutic

    Before After 2 Months of Montelukast

    MMSE 22: mild dement

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