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10/17/2017 Copyright by Dr. TC Theoharides 1
Theoharis C. Theoharides, MS, MPhil, PhD, MD, FAAAAI
Professor of Pharmacology, Internal Medicine and PsychiatryDirector, Molecular Immunopharmacology and Drug Discovery
Tufts University School Medicine, Boston, MA, [email protected]
www.brain-gate.orgTax-deductible donations for our
research at:giving.tufts.edu/theoharides
110/17/2017 Copyright by Dr. TC Theoharides
Intranasal Administration of Methylated Luteolin for Treatment of Autism
Market Overview
Fast Facts
Relative Market Size
Population Afflicted – Volume
Trend Line in Spending growth showing it corresponds with population - extrapolate
• Domestic Autism diagnosis nearly doubled between 2004 and 2016
• As of 2008, Autism is the fastest growing developmental disorder in the United States
• The cost of Autism are more than double the costs of stroke and hypertension, combined
• By 2025, Autism costs are projected to be between $276 billion to $1 trillion
• No treatment for Autism exists, only treatment to mask some of its symptoms
$379
$265
$0
$100
$200
$300
$400
Prescription Drugs Autism Treatment and Care
Domestic Therapeutics Market 2015Billions, USD
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Wong AY et al., Autism Res. 2014 Oct;7(5):543-54
Most Countries Use Psychotropic Drugs for ASD
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Neurotensin, Histamine &
Tryptase
IL-6, TNF
MicrogliaMast cell
Cross-talk Between Mast Cells and Microglia Leading to Inflammation of the Brain
IL-1β, IL-6, TNF & CCL2, CCL5, CXCL8
Pro-inflammatory mediators
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Diencephalon(coordinates sensory input and emotions)
Mast Cell Activation
Dysfunctional social behavior, communication and stereotypic
movements
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Autism Spectrum Disorders and MastocytosisTheoharides TC. Int J Immunopathol Pharmacol. 2009 Oct-Dec;22(4):859-65.
The risk of autism was 10 times higher than in the general population.
Neuronal excitation
Microglial activation
Mast cell stimulation
CCL2, IL-1β, IL-6 & TNF
Histamine & Tryptase
Luteolin& methoxyluteolin
Neurotensin
NTR1
NTR3
NTR1
Inflammation of the Brainin Autism
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Mast Cell
Microglia
Inflammatory mediators
Neurons
Neuronal damage and impaired connectivity
Autism
Environmental Triggers(Aluminum, Bisphenol A, Mercury, Organophospates, Polychlorinated biphenyl)
No trigger Triggers +Atopy+ CRH+Neurotensin+ mTOR activation
Triggers +Atopy
Triggers
INSCREASED RISK OF AUTISM
Triggers +Atopy + CRH+Neurotensin
Methylated luteolin
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Proposal
Facts• NIH gave $125 million for Autism in 2017, but none of it for
inflammation of the brain• Autism Speaks and ARI do not give grants any moreProposal• Raise $3 million over 5 years• Develop liposomal methoxyluteolin for intranasal delivery to the brain• Determine inhibition of human mast cells and microglia• Obtain proof of principle in mouse autism model• Conduct pilot clinical trial in humans• Submit SBIR applications for funding
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