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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
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● 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)
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● 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!!
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● Very important piece of the picture of autism
● Much more complicated than you have ever heard of…
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● HISTORY OF MELATONIN
● SCIENTIFIC PRINCIPLES
● ACTIONS OF MELATONIN
● SIGNIFICANCE TO PATIENTS WITH AUTISM
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● 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
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● 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”)
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
What the BODY does to a CHEMICAL
PHARMACOKINETICS
What the CHEMICAL does to the BODY
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● 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
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
MESENTERIC VEINS
PORTAL VEIN
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● Maintain Circadian rhythms
● Sleep
● Body temperature
● Hormone regulation
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● Depends upon tissue location:
PINEAL GUT
timing night 24/7
stimulus light food
location blood
(central) enterohepatic
(local)
actions sleep pleitropic
(metabolic)
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● PLEITROPIC ACTIONS
● Metabolism
● Immunoregulation
● Antioxidant
● Anti-inflammation
● Metallochaperone
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● 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
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● Metabolism
● Supports MICROBIOME
● Bacterial flora in gut
● Enormous impact on health
● Digestion of food
● Controls growth of “PATHOGENIC BACTERIA”
● Prevents development of “LEAKY GUT”
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● Immunoregulation
● Supports “Th1 phenotype”
● (cell-based immunity)
● Maintains glutathione concentrations
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● Antioxidant
● More potent antioxidant than “antioxidants”
● Vitamin C or Vitamin E
● Reduces oxidant stress
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● Anti-inflammation
● Blocks cytokine production and signalling
● Reduces white blood cell (leucocyte) migration
● Maintains integrity of mitochondria
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● Metallochaperone
● Maintains trace metals nutriture
● Zinc, copper, selenium, manganese
● Zinc is most important trace metals
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
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”)
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● 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
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● “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
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
● 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
© 2016 Syncratic Therapies, LLC Presentation to AutismOne
(please visit www.melascend.com)