Download - Rejuvenation of the Aged Brains2.q4cdn.com/.../2016/Aigner-IntelgenX.pdf · Ludwig Aigner IntelGenx, Grand Opening, Saint-Laurent, May 10th 2016. ... Institute of Molecular Regenerative

© 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


TOMORROW


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


Massive Increase in the Prevalence of AD


GeneticNon-Genetic

Alt


Alzheimer Pathology


Are We Targeting the Right Thing ?

Rodrigue et al., Neuropsychol Rev. 2009


1001 Reasons for Neuronal Cell Death ???


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


AGING and REJUVENATION







Demyelination

Axonal Damage


The Aged Brain is a „Diseased“ Brain

Regeneration

Disease RiskDisease Risk

Live = Aging

Growth Plasticity Degeneration Disease


Growth Plasticity Degeneration

Aging and Rejuvenation

„Regenerative Pharmacology“

Disease



Can We Turn Back the Clock ?


Muscle Research, Aging, and Regenerative Medicine ?


inflammation

neurogenesis

cognitiion

Modulating the Systemic Milieu: a Valid Approach


Eotaxin Reduces Neurogenesis

Eotaxin Worsens Cognition

Old Blood Contributes to Brain Aging

EOTAXIN


Eotaxin Leukotrienes

Allergy / Asthma Brain Aging

Aging / Degeneration


Leukotrienes Impact on Brain Aging

Leukotrienes






Demyelination

Axonal Damage


Monte

lukast

Proof of Principle:

Inhibition of Leukotriene Receptors Improves Cognition in Aged Rats


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


**

Learning Memory

*

Montelukast Improves Cognitive Functions in PD / LBD Animals



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sAnnual Counts of Publications “Drug Repurposing”


“All De- and Regenerations are Similar”


REPAIR

REPLACE

RESTORE

REGENERATE

REJUVENATE

Regenerative Medicine

All Organs

Different Diseases


MMSE 13: moderate to severe dementia

Montelukast as an Anti-Dementia Therapeutic

Before After 2 Months of Montelukast

MMSE 22: mild dementia


Discover

y

Preclini

c

Phase

I

Phase

II

Phase

III

Approval

BIOTECH

Academia Big Pharma


Let‘s make a better Montelukast

Download - Rejuvenation of the Aged Brains2.q4cdn.com/.../2016/Aigner-IntelgenX.pdf · Ludwig Aigner IntelGenx, Grand Opening, Saint-Laurent, May 10th 2016. ... Institute of Molecular Regenerative

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