Paradigm Shift in Models of Autism (adapted from Martha Herbert, PhD)

1. Paradigm Shift in Models of Autism (adapted from Martha Herbert, PhD)

2. Four Vicious Cycles Slide courtesy of Dr. Liz Mumper

3. TREAT AUTISM AS A MEDICAL, NOT PSYCHIATRIC DISORDER! There Are5 MAJOR MECHANISMS With Evolving Biomarkers That Give Us Strong Clues So We Can Effectively Oxidative Stress Methylation & Transsulfuration Toxins & Heavy Metals Immune System Dysregulation Gastrointestinal Inflammation TREAT

4. Expensive Inexpensive Global number of responses Limited number of responses Cost to Benefit Comparisons Must Be Considered Relative to Every Family’s Unique Circumstances

5. Relative Cost for Treatment Examples: MB12, Diets, Epsom salts Examples: HBOT, Colonoscopy, IVIG

6. Relative “Global” Benefits Examples: Epsom salts, Melatonin Examples: MB12 HBOT, IVIG

7. BIOMEDICAL TREATMENT PRINCIPLES • Remove or reduce dietary stressors • Remove or reduce environmental stressors • Remove or reduce inflammation • Improve nutritional support • Improve damaged biochemistry • Improve immune function • Improve detoxification Philosophy: “Break the Gridlock”

8. Referral for colonoscopy IV therapies Methyl-B12 Methyl-B12 Early testing (?) Anti-viral Tx HBOT LDN, Actos Diet Treat allergies Supplements “Chelation” Heal the gut Treat infections Philosophy: Test only if it will affect treatment

9. It’s Time To Talk About What Treatments Use Your Time And Spend Your Money Most Wisely! Works most of the time Works some of the time Works a little bit of the time

10. It’s Time To Talk About What Treatments Use Your And Spend Your Most Wisely! • Methylcobalamin: SQ • Hyperbaric Oxygen • IV Chelation • Healing the Gut • Diets • Supplements • Other IV Therapies 50% to 90%Response Rate

11. It’s Time To Talk About What Treatments Use Your And Spend Your Most Wisely! • Non-IV chelation • Antivirals • Modified Genomics • IVIG • Glutathione, non-IV • Allergy Treatment • Melatonin • Epsom salt baths, MSM 25% to 50%Response Rate

12. It’s Time To Talk About What Treatments Use Your And Spend Your Most Wisely! • LDN • Actos (PPAR) • Homeopathy • Metallothionein promoter • Secretin • Sauna, e.g. FIR • “Natural chelation” • GABA • L-theanine • DMAE • DMG • Vitamin A/Bethanecol • TTFD • Transfer factor • NAET • PANDAS • Chiari malformation • Creatine • ALA & TD-ALA • “Zeolite” • “Liver Life” • “NDF & NDF Plus” 5% to 25% Response Rate

13. It’s Time To Talk About Treatments That Are New Or Being Tried In Different Ways That May Have Promise • Oxytocin • Spironolactone • Thyroid • Lyme disease • Lowering testosterone • D-penicillamine chelator • Minocycline • COX inhibitors • Stem cells • “Biofilm” Variable Response Rates New and Exciting Times Clinicians Are Not Yet In Agreement About These

14. And Methyl-B12 Some Children Defy the Odds And “Average” Has No Bearing On Individuality! A Good Example Is Secretin

15. Methionine BHMT The Methylation and Transsulfuration Pathways Provide the Reduced Glutathione (GSH) to Repair Oxidative Damage. Mg FOLATE CYCLE TRANSMETHYLATION THF B6 SAM Methyl acceptor DMG MS MSR 5,10-CH2-THF Methyl transferase  B12 Trimethylglycine Methylated Product (DNA, RNA, Protein, Neurotransmittors) MTHFR SAH 5-CH3-THF SAHH Zn Homocysteine Adenosine B6 CBS Cystathionine Cell membrane B6 TRANSSULFURATION Cysteine Glutathione Peroxide Reactive Oxygen Species: Peroxides GST M1 GSH GSSG NULL Slide courtesy of Dr. Jill James and Dr. Jeff Bradstreet

16. A Power Player Methyl-B12 Executive Function Socialization Emotion Speech & Language

17. CH3 CH3 Vending Machinesof the Mind GA (Creatine) Phospholipids Neurotransmitters Etc!

18. The Methyl-B12 Grandfather Clock Pays for education to “make the brain smart” Methylation Transsulfuration Pays the body’s firemen and garbage collectors to “keep the body safe, clean, and comfy”

19. The Methyl-B12 Clock Methionine SAM Methyl-B12 (with Methionine Synthase) SAH Homocysteine Cysteine The Methylation Transsulfuration Pathways Glutathione

20. The “Car” at the Crossroad is Homocysteine Methionine SAM B12 SAH Homocysteine And Mr. Methyl B12 “Drives” the Car Cysteine Glutathione Cysteine (Not Adenosyl, Cyano, Hydroxy, or Glutathionyl B12 )

21. CONSERVED Methionine SAM Methyl-B12 SAH Methionine Synthase Homocysteine Homocysteine Homocysteine Cystathionine B-Synthase CONSUMED Homocysteine Traffic Is Directed By Two Enzyme Traffic Cops Glutathione

22. Executive Function Speech & Socialization Methionine SAM Methyl-B12 CONSERVED SAH Hg, Pb Heavy Metals Toxic Chemicals HOMOCYSTEINE Free Radicals Runaway Electrons Infections CONSUMED Glutathione

23. FOLIC (“FOLIAGE”) ACID CYCLE Methionine Methylation Potential (SAM/SAH) THF SAM MTase 1 2 Cell Methylation 5,10-CH2THF BHMT MS SAH B12 Betaine MTHFR 5-CH3 THF SAHH Choline Adenosine Homocysteine 1 Folate Cycle Methionine Cycle Transsulfuration Pathway CBS B6 Cystathionine 2 Antioxidant Potential GSH/GSSH 3 Cysteine 3 GSH GSSG

24. FOLIC (“FOLIAGE”) ACID CYCLE Methionine Homocysteine THF 5,10-CH2THF Methyl ticket MS MTHFR 5-CH3 THF By using the methyl ticket that was sold by Mr. MTHFR, one can get on the MT Line and take a train ride to make “brain things” while “putting out fires” and “cleaning house!” B6

25. The “brain form” of methionine synthase is critically different from the “body form” of methionine synthase HCY Domain SAM Domain Brain Body Cobalamin (vitamin B12) 5-methyl THF Domain Cobalamin Domain Cap Domain Richard Deth, PhD with JN, MD

26. Without the Cap or SAM domains, oxidized B12 will readily dissociate and must be continuously replaced by more methyl-B12 Methyl-B12 Is The Cobalamin That Works Best With Methionine Synthase In The Brain HCY Domain IN THE CORTEX SAM Domain M-B12 Cobalamin (vitamin B12) 5-methyl THF Domain Cobalamin Domain Cap Domain Richard Deth, PhD with JN, MD

27. Response Rate and Intensity of Responses for Methyl-B12 • Subcutaneous: Range 80% to 94% Global responses out of 135 Average 30-45 or more! • Nasal: Range 25% to 60% (most say 25% to 30%) Far less global responsiveness • Transdermal: Range 5% to 8% Minimal global responsiveness • Oral: Range 3% to 5% Minimal global responsiveness • Sublingual: Not used; ineffective • TMG blocks MB12 effects because BHMT competes with MS!

28. MECHANISMS OF ACTION FOR HBOT • Angioneogenesis from the addition of O2. • Angioneogenesis from the removal of O2. • Increases in blood flow independent of new blood vessel formation. • Decreasing levels of inflammatory biochemicals. • Up-regulation of key antioxidant enzymes and decreasing oxidative stress. • Increased oxygenation to functioning mitochondria. • Increased production of new mitochondria • Bypassing functionally impaired hemoglobin molecules secondary to abnormal porphyrin production. • Improvement of the immune system and the autoimmune system.

29. Decreasing the bacterial and yeast load systemically and in the gastrointestinal system. • Decreasing the viral load found systemically and the viral load in the gastrointestinal mucosa. • Increases in the production of stem cells in the bone marrow with transfer to the central nervous system. • Direct production of stem cells by certain areas in the brain. • Increased production and utilization of serotonin. • The possibility that oxidation may help rid the body of petrochemicals (theoretical only). • The possibility that oxidation may help rid the body of mercury and other heavy metals (theoretical only).

30. Cell Density High Cell Density Low Inflammatory Presence Ann Neurol. 2005 Jan;57(1):67-81

31. Neuroscience Letters 241 (1998) 17–20 Sweeten et al., 2003 Am J Psychiatry 160(9):1691-3 ~3 ½ X greater than controls! Inflammatory Presence

32. Connolly et al., 1999 J Pediatr 134:607-13 Bad! Good!

33. Oxidative Stress and HBOT • At pressures below 2.0 atm, HBOT can decrease oxidative stress by increasing anti-oxidant enzyme levels such as: • Superoxide dismutase (SOD) • Catalase • Glutathione peroxidase • Heme-oxygenase-1 • At pressures above 2.5 atm, HBOT may actually increase oxidative stress

34. Before After Mild HBO SPECT Scans in a 4 y.o. Autistic Child After 10 Treatments Using 1.3 atm and 24% O2 Blue Lips Red Cheeks Heuser et al., 2002 Best Publications; 2002:109-15

35. The Results of >30,000 Hours of HBOT Treatments Using 1.3 and 1.5 ATA The 20 Most Common Parental Observations • Activity: more age appropriate activity (in contrast to true hyperactivity). • Attentive, more: “S/he’s now just ‘with us’ where before s/he wasn’t”. • Awareness: increased in general. • Bowel function: better stools, change in frequency, consistency, character of stool; able to potty train fully or more quickly than before. • Conversational language: more free speech; interjects own words [sounds, babble] as attempts to be part of family or therapy interaction; speech flows more freely; longer sentences at appropriate times. • Eye contact: improved, turns to the person who is calling or talking; “curious” about eyes and “the meaning” of other’s eyes; holds eye contact longer. • Feelings: more in touch with his/her own feelings; understands others feelings or expressions; has higher highs and lower lows in a more normal way of being.

36. The Results of >30,000 Hours of HBOT Treatments Using 1.3 and 1.5 ATA The 20 Most Common Parental Observations • Gestures are more appropriate; better use of body language to communicate wants, needs, and desires; requests that you attend to his/her emotional or physical needs. • Good days: more, better, or of a different nature and quality than seen by family or reported by school and therapists. • Happier: a greater general sense of feeling good about his/her self and life in general; demonstrates an attitude that says, “Something about my life is different and better today.” • Hyperactivity: more (true hyperactivity not to be confused with a child being more age appropriately active). • Opinions: has his/her own opinions and definitely lets you know what they are more than ever before, e.g. s/he expresses more freely and/or more appropriately his/her likes or dislikes, e.g. “the I don't want to's because I'm happy doing what I'm doing and I have my rights, you know!”, etc. • Independent: new level of self-assuredness, self-confidence, attempting to do things on his/her own; “self perceived ‘appropriate’ anger or irritation for you not letting him/her do something he/she feels perfectly capable of now doing on his/her own”.

37. The Results of >30,000 Hours of HBOT Treatments Using 1.3 and 1.5 ATA The 20 Most Common Parental Observations • “Presence”: more involved; more “with it”; seems much more attune to what is happening on a day-to-day basis and in the world aound him/her. • Requests: makes his/her needs known to family, friends, playmates. • Self confidence: now present for the first time or greater than before treatment; seems proud of himself/herself and his/her accomplishments; wants and/or demands you acknowledge what s/he has done; expects praise and “proudly glows” when it is given. • Sentence structure: longer; more complete; more complex; better structured; uses adjectives, adverbs, prepositions, pronouns, etc. • Spontaneous speech: more frequently initiates conversation; talks more without prompting or just echoing or repeating. • Verbalization or vocalization increasing and/or more appropriate, "babbling" increasing; more sounds being made or attempted. • Vocabulary: knows more words ; knows words no one ever taught; you find yourself “surprised” that s/he said such-and-such; vocabulary is used more appropriately.

38. All Reporting Facilities, All ChemicalsTRI-(1987-2002) Map shows 3,683 of 48,205 facilities reporting nationwide Largest Mercury Mines Largest Mercury Mines Potential association between autism rates, environmental mercury other toxins in TexasPalmer, et al., Health and Place 2006 Jun;12(2):203-9 Autism rates On average, for each 1000 lb of environmentally released mercury, there was a 43% increase in the rate of special education services and a 61% increase in the rate of autism. Total toxicity Chemicals-TRI

39. "Breaks" "Damage" "Death"

40. It's Stuck Tight Inside!

41. Mercury and autoimmunity: implications for occupational and environmental health. Toxicol Appl Pharmacol. 2005 Sep 1;207(2 Suppl):282-92. Silbergeld EK, Silva IA, Nyland JF. Department of Environmental Health Sciences, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA. Mercury (Hg) has long been recognized as a neurotoxicant; however, recent work in animal models has implicated Hg as an immunotoxicant. In particular, Hg has been shown to induce autoimmune disease in susceptible animals with effects including overproduction of specific autoantibodies and pathophysiologic signs of lupus-like disease. and antinucleolar antibodies and a positive interaction between Hg and malaria. These results suggest a new model for Hg immunotoxicity, as a co-factor in autoimmune disease, increasing the risks and severity of clinical disease in the presence of other triggering events, either genetic or acquired. A Co-factor in Autoimmune Diseases!

42. Oral & Suppository Chelation Work Very Well! It’s Time To Get Moving Before Time Runs Out! Oral or suppository DMSA Oral or suppository DMPS Suppository EDTA • Non-IV chelation • Antivirals • Modified Genomics • IVIG • Glutathione, non-IV • Allergy Treatment • Melatonin • Epsom salt baths, MSM (Transdermal Is Somewhat Limited?)

43. Intravenous Chelation Works Very Well! It’s Time To Get Moving Before Time Runs Out! IV "Calcium" EDTA • Methylcobalamin: SQ • Hyperbaric Oxygen • IV Chelation • Healing the Gut • Diets • Supplements • Other IV Therapies IV DMPS

44. Healing The Gut Is Mandatory For Success! • Major Antifungals • Minor Antifungals • Major Antibacterials • Natural Agents • Special Diets • Probiotics • Digestive Enzymes • Major Anti-inflammatories

45. Lymphonodular Hyperplasia Apthous Ulcers Autistic Enterocolitis Histopathology is Similar to Crohn’s

46. Autism Inflammatory 25 I.B.D. Normal 20 15 10 5 0 CD3 CD4 CD8

47. Bad Bacteria Bad Yeast Leaky Gut

48. It’s Time To Get Moving Before Time Runs Out! • Organic F/V (Jim Adams et.al.) • CFGF (Karen Serousi, Lisa Lewis) • SCD (Elaine Gotschall) • Feingold • Elimination/Rotation • Candida (Crook, Truss) • Low Oxalate (Susan Owens)

49. It’s Time To Get Moving Before Time Runs Out! • B6 & magnesium (Dr. Bernie Rimland) • Cod liver oil • Essential fatty acids • Zinc • Other B vitamins • Other macro & trace minerals • Amino acids

50. Same Amount Of Food Water The Difference Nutritional Value! It’s Time To Get Moving Before Time Runs Out! Courtesy of Don Davis, PhD