David Kossor, PhD, RPh, DABT, PMP May 26, 2016 · 2016. 5. 22. · David Kossor, PhD, RPh, DABT,...

David Kossor, PhD, RPh, DABT, PMP

Syncratic Therapies, LLC

Presentation to AutismOne

May 26, 2016

© 2016 Syncratic Therapies, LLC Presentation to AutismOne

INSPIRE

MOTIVATE

EDUCATE


● Concept first appeared by Charles Darwin in 1857

● Pertained to genetics

● Splitter = increased diversity

● Lumper = reduced diversity

● Has been expanded to describe research paradigms

● Splitter = divergent approaches (data-driven)

● Lumper = convergent approaches (concept-driven)


● BOTH concepts are needed to advance science:

● Splitters generate the pieces of a puzzle

● Lumpers assemble the pieces to create a picture

● Splitters vastly outnumber Lumpers

● Splitters generate DATA that support GRANT FUNDING

● PEER-REVIEW

● Lumpers are PIONEERS

● By definition… PIONEERS HAVE NO PEERS!!


● Very important piece of the picture of autism

● Much more complicated than you have ever heard of…


● HISTORY OF MELATONIN

● SCIENTIFIC PRINCIPLES

● ACTIONS OF MELATONIN

● SIGNIFICANCE TO PATIENTS WITH AUTISM


● Discovey by Aaron Lerner in 1958

● Affected melanin deposition in skin

● Might be beneficial in treatment of skin disorders

● “hormone of darkness”

● Produced by pineal gland in brain

● Stimulus: reduced light during evening hours

● Dominated research efforts for 40+ years

● Professor

● UT Health Sciences Center

● Dept. of Cellular & Structural Biology

● Functional significance of melatonin in aging processes

● Editor-in-chief

● Journal of Pineal Research

● Accomplished Splitter AND Lumper



● Endogenous (= made inside the body)

● Pineal gland

● Gastrointestinal tract, retina, placenta, etc.

● Exogenous (= Taken in from the outside)

● Oral (food; pills)

● Parenteral (injection)

Transcutaneous (skin “patch”)


What the BODY does to a CHEMICAL

PHARMACOKINETICS

What the CHEMICAL does to the BODY


● ABSORPTION

● Rapid absorption across biological membranes (lipophillic!)

● DISTRIBUTION

● Rapid tissue uptake

● Biliary excretion

● HIGHEST CONCENTRATION IN BODY

● 100-1000 TIMES GREATER THAN BLOOD

● Enterohepatic circulation

● CYCLES BETWEEN THE GUT AND THE LIVER


MESENTERIC VEINS

PORTAL VEIN


● Maintain Circadian rhythms

● Sleep

● Body temperature

● Hormone regulation


● Depends upon tissue location:

PINEAL GUT

timing night 24/7

stimulus light food

location blood

(central) enterohepatic

(local)

actions sleep pleitropic

(metabolic)


● PLEITROPIC ACTIONS

● Metabolism

● Immunoregulation

● Antioxidant

● Anti-inflammation

● Metallochaperone


● Metabolism

● Infancy

● Melatonin is supplied by breast milk

● Health implication of premature weaning

● Melatonin is highest during pre-adolescence, then declines through life

● Diminished melatonin stimulates estrogen/testosterone production

● Diminished melatonin signals onset of puberty


● Metabolism

● Supports MICROBIOME

● Bacterial flora in gut

● Enormous impact on health

● Digestion of food

● Controls growth of “PATHOGENIC BACTERIA”

● Prevents development of “LEAKY GUT”


● Immunoregulation

● Supports “Th1 phenotype”

● (cell-based immunity)

● Maintains glutathione concentrations


● Antioxidant

● More potent antioxidant than “antioxidants”

● Vitamin C or Vitamin E

● Reduces oxidant stress


● Anti-inflammation

● Blocks cytokine production and signalling

● Reduces white blood cell (leucocyte) migration

● Maintains integrity of mitochondria


● Metallochaperone

● Maintains trace metals nutriture

● Zinc, copper, selenium, manganese

● Zinc is most important trace metals


Essential for over 300 zinc-dependent enzymes

● DNA/RNA production & repair

● Carbonic anhydrases (ionic balance)

● Matrix metalloproteinases (collagen metabolism)

● Aminopeptidases/carboxypeptidases (protein digestion)

● Alcohol dehydrogenase (degrades ingested ethanol)

● “ZINC FINGER PROTEINS” (cytokines/growth factors)

● Tight junction proteins (prevents “leaky gut”)


● Toxicants decrease melatonin in the gut

● Healthy people restore the intestinal pool

● Patients with autism can’t restore the pool

● Deficient methyl transferase enzyme

● Deficient methyl donor

● Both


● “Typical” oral melatonin tablets deliver melatonin to the blood

● may be helpful for insomnia

● Special formulation needed for gastrointestinal delivery

● Melascend® = MEDICAL FOOD ● Defined by the Food & Drug Administration in 1990

● Supervised by healthcare provider

● Specially formulated to restore the enterohepatic cycle of melatonin


● Melatonin is produced at several locations in the body

● Melatonin has important pleitropic actions

● Melatonin is deficient in many patients with Autism

● Patients with Autism may benefit by taking Melatonin

● Melascend® is needed to restore Melatonin in the gut

● We can work with healthcare provider s to develop specific dosage regimens for individual children


(please visit www.melascend.com)

David Kossor, PhD, RPh, DABT, PMP May 26, 2016 · 2016. 5. 22. · David Kossor, PhD, RPh, DABT,...

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