William Walsh - Pfeiffer/Metallathionein

William Walsh - Pfeiffer Institute
Is a Not-for-Profit out-patient organization. They treat patients who come with a diagnosis of behavior, ADD, autism – mainly deal with chemical imbalances. They deal a lot with methylation disorders and Essential Fatty acids. These are very individualized treatments. The weapons they use are nutrients, amino acids, vitamins, minerals Look for chemicals to form in the body.  He said when traditional medical doctors, ask what the Pfieffer Institute is doing, he said the traditional doctors are looking for traditional meds. When Dr. Walsh gets to the part about vitamins, minerals, and nutrition, the medical doctors tend to tune out at that point.

Where do neurotransmitters come from? The brain is a chemical factory. The body creates all the chemicals. They know where in the brain these are produced. Nutrients are the raw materials…vitamins, minerals, amino acids. Getting the wrong ones to the brain in the wrong quantities can cause problems. They deal with balancing the brain chemistry.  Takes various populations and studies their chemistry – have an extensive chemistry. They have taken the data base of behavior disorders and they fall into 4 major chemical classification. 5 major types of depression for example.

Slide 1. Year 2001 discovery: Metallothionein (MT) Dysfunction in Autism
- Absence of Cu, Zn Regulation in Blood
- MT Proteins Responsible for Cu, Zn Regulation
- MT Dysfunction consistent with Classic Autism Symptoms
Notes: MT Dysfunction occurs in almost all autistics. They looked through their database of patients that clearly were diagnosed with some form of autism and did not have another co-existing diagnosis.

The remaining 503 patients comprised the test population for this study.

Slide 2. Abnormal Metal-metabolism throughout the autism spectrum
Autistic Disorder (318)
PDD with Autistic Features (162)
Asperger's Disorder (23)
>The incidence and severity of metal imbalances were very similar across these autism phenotypes.

3. Test Population
The test subjects were selected from a pool of 705 patients previously diagnosed with an autistic-spectrum disorder. Using DSM-IV subjects with questionable diagnoses, and patents with co-morbidity for seizures, depression, schizophrenia, serious head injury, Tourette's Syndrome, . and birth anoxia were excluded (deprived of oxygen).

4. Abnormal Metal-metabolism Observed in Test Subjects
- extremely disordered levels of Cu and Zn, indicating absence of blood homeostasis for these metals in 428 subjects (85%),
- moderately disordered Cu/Zn levels despite ongoing zinc therapy in 41 subjects (8%)
- Severe pyrrole disorder in an additional 30 subjects (6%) indicating severe zinc depletion
- only 4 of the 503 autism-spectrum patients did not exhibit a serious metal-metabolism disorder.
>These data strongly suggest a universal metallothionein protein dysfunction in autism-spectrum patients

5. showed a line graph showing that the Cu/Zn rations in autistics were clearly higher than NT control group.

6. Experimental Results and Statistical Analysis
The mean Cu/Zn ration for autism spectrum patients was 1.63 and for controls 1.15. The controls were matched for age and gender.
Notes: Extremely disordered levels of Cu and Zn, indicating absence of blood homeostasis for these metals in 428 subjects (85%)

7. graph showing the amount of excessive unbound CU in 100% of autistics (number of individuals in sample = 22).
Notes: Moderately disordered Cu/Zn levels despite ongoing zinc therapy in 41 subjects (8%)
Severe pyrrole disorder in an additional 30 subjects (6%), indicating severe zinc depletion, Only 4 of the 503 autism-spectrum patients did not exhibit a serious metal-metabolism disorder.  Found a lot of unbound copper in the plasma – this is usually managed by MT. The level of unbound copper was 4 times larger in the blood of autistics.

8. Primary Functions of Metallothionein
-Development of brain neurons
-Cell transciption
-Homeostatic control of Zn and Cu
-Detoxification of heavy metals
-Maturation of the GI tract
-Powerful antioxidant
-Immune Function
-Delivery of Zn to cells
Notes: When mercury binds to MT it leaves the body easily. It is a marvelous antioxidant in the body – when MT is down, the radicals are loose.

9. A recipe for Autism
- genetic impairment of MT functioning – not so much one defective gene, but one of several genetic causes that disables MT because many
things must come together to get MT to function properly. Any one of those many things can cause problems.
- environmental insults(s) which disables MT

10. Possible Causes of MT Dysfunction
- genetic MT defect
- genetic disorder which disable MT
- environmental insult which disables MT

11. Genetic Impairment of MT Function
-Tenuous MT Support for Neuronal Development
- Hypersensitivity to mercury, lead, and cadmium
- hypersensitivity to infections and vaccines

12. Environmental Insults Disable MT
-Incomplete Maturation of Brain and GI Tract
-Build Up of Toxic Metals - Hg Pd, Cd, etc.
-Cu overload & Zn Depletion
-Impaired Hippocampal Function
-Weakened Immune Function
> Restoration of MT function may be blocked by excessive build-up of copper and toxic metals
It does look like this MT dysfunction can be restored.

13. The MT Protein Family
- Mt-I and MT-II are present in all cells throughout the brain and periphery
- MT-III is a neuronal growth-inhibition factor found primarily in the brain
- MT-IV is found primarily in epithelia of skin and GI tract.

14. Human MT
-Family of cysteine-rich proteins
-Short linear arrays of sixty-one to sixty-eight amino acids
-S configuration with extraordinary metal-binding capability
- Induced by Zn, Cu, toxic metals, physical trauma, and emotional stress

15. Expected Consequences of MT Dysfunction
(list of what you would expect to see with MT dysfunction)
- Hypersensitivity to HG, PB, and other toxic metals
- Zn depletion and Cu overload
- Hypersensitivity to vaccines
- Incomplete breakdown of casein and gluten
- Intestinal inflammation, diarrhea, and yeast overgrowth
- Reduced stomach acid and diminished secretin release
- Tendency for seizures, anxiety, and emotional meltdowns
- MT kills candida (so overgrowth is common when MT is stopped)
- Higher vulnerability for males than females (because hormones factor into this somehow and boys have more of one type than girls)

16. Detoxification of Toxic Metals
- Mt is the body's primary protection against toxic metals: MT is a "magnet" for mercury, lead, cadmium, etc.
- Intestinal MT provides a barrier to absorption of ingested toxic metals
- MT in periphery and brain sequesters and deactivates toxic metals.
Notes: 95% of mercury is grabbed by MT right off and MT grabs other remaining metals at blood-brain barrier

17. MT Dysfunction causes Cu/Zn Imbalance
- Tendency for rages and emotional meltdowns
- ADHD is associated with Cu/Zn imbalances
- Impaired hippocampus and amygdala functioning which causes emotional memory and socialization deficits. Amygdala – when not
functioning, they will not initiate social approach, ritualistic behavior, hard time interpreting facial expressions.
- Dopamine/norepinephrine imbalance – Cu is involved in this conversion
> Normalizing Cu and Zn levels in blood is an important component of autism therapy. One nice thing is we can normalize the amounts of

18. MT and Immune Functions
- Deletion of MT compromises in-utero development of thymic and lymphoid tissue
- MT depletion reduces production of T cells, IL-2, thymulin, NK cells, etc.
- MT knockout mice exhibit severely weakened immunity – when MT is taken out of mice they have extraordinary weakened immunity

19. MT Impact on Casein and Gluten
Casein/gluten peptides are broken down by Zinc dependent enzymes (carboxypeptidase A, aminopeptidase, etc ); MT dysfunction is
associated with sever zinc depletion and reduced production of these enzymes.  Diminished MT in GI tract results in increased levels of unbound
mercury, lead, cadmium, etc. which can disable enzymes that break down casein and gluten.
>Correction of MT disorder may eliminate need for a casein/gluten free diet.

20. Role of MT 1 and MT 2 in intestinal mucosa
- Barrier to penetration of Hg, Pb, and Cd into the blood stream
- Regulation of copper absorption
- Combats inflammation
-Kills candida. – MT helps prevent yeast overgrowth
>Normalization of MT may eliminate tendency for intestinal inflammation, leaky gut, and yeast overgrowth in autism.

21. Impact of MT-IV Dysfunction
-Reduced production of stomach acid
---incomplete food processing in stomach
---Impaired secretin signaling
---reduced amounts of gastrin, carbonate, etc.
-Sensitivity to taste and food texture
-Skin sensitivity

22. MT dysfunction and seizures
- MT knockout mice exhibit high incidence of seizure
- Zn released by hippocampal MT-1 decreases seizure activity

23. Explanation of higher autism incidence in males
- MT synthesis is enhanced by estrogen and progesterone, especially during early development.
- Females have higher estrogen and progesterone level than males
- Therefore, females are better protected against environmental insults which can trigger autism

24. Genetic Aspects of autism
-Strong genetic predisposition in autism
---Higher concordance in siblings
---60% concordance in identical twins
- Influence of Environmental Factors
---Identical twin concordance not 100%
---Dramatic differences in identical twins
>This suggests that the cause of autism is a genetic predisposition followed by an environmental insult during early development.

25. Metallothionein Theory of Autism
- Genetic MT dysfunction results in hypersensitivity to toxic metals and viruses.
- Environmental insults during early development provoke autism: In utero insults results in autism at birth; early childhood insults provoke regressive autism.
>After age 3, the brain and GI tract have matured to the point that environmental insults can no longer provoke autism.

26. The Onset of Autism
-Genetic weakness in MT system – not a defect, a weakness
-Environmental Insult disables MT
---Toxic Metal Poisoning
---Viral Assault
---Zinc Depletion
- Temporary Disruption of Neuronal Development : Brain, GI tract

27. Timing of Environmental insults in important
In-utero - autism evident at birth, greater severity of symptoms, mental retardation often present
After Birth – Regressive autism, symptoms depend on developmental stage during insult
>After age 3, the brain and GI tract have matured to the point that environmental insults can no longer provoke autism.

28. Severity of these insults in important – when in the developmental development did this happen
- Example: MT disruption during development of speech center
Mild insult – speech delay
Severe Insult – mutism

29. There is a biochemical aftermath and a physical aftermath.
The Biochemical Aftermath
-Disabled MT system
-Copper overload
-Toxic metal overload
-Zinc depletion
-Neuro-transmitter imbalances
***Each of these biochemical conditions may be correctable

30. Physical Aftermath
-Incomplete maturation of brain
-High incidence of GI tract problems
-Compromised immune function
-Disruption of hippocampus/amygdala functioning
***Each of these conditions may be treatable
He sensory integration therapy showers the impulses trying to develop new brain cells and develop neural connections. It can be very effective, but often slow. They would like to find a way to speed this process up.

31. Autism Prevention Steps
- Prenatal Avoidance of environmental Insults: Toxic metals, Vaccines, Medications, Dental procedures involving amalgams
-Early infant screening for Autism predispositions: Genetic screening, MT protein testing, Testing of Cu, Zn, ceuloplasmin
-Avoidance of Environmental Insults in Autism-Prone children – amalgams, fish, Flu shots during pregnancy
>They are trying to get some commercial tests so screening can be done.

32. Biochemistry of Metalothionein
-Induction of thionein
-Proloading with zinc assisted by Glutathione SH (need 7 zincs/MT)
-GSH/GSSH redox couple enables Zn delivery and /or sequestering of toxic metals
-MT activity enhanced by Zn, GSH, Se, Genistein, Biochanin, Vitamins, A, C and E.

33. A Lesson From Wilson's Disease
-Wilson's disease is copper overload disease which disables MT
-Two-phase treatment is effective
Step 1: removal of excess Cu
Step 2: long-term maintenance using Zn therapy – in Autism need to remove all metals.
>Autism therapy requires removal of Cu and toxic metals

34. Autism Treatment Protocol
- GI tract therapies: Clean up the gut first – GFCF diet, probiotics, secretin, digestive enzymes, dysbiosis treatment, etc.
- Biochemistry Balancing: Methylation, trace metals, pyrroles, essential fatty acids, etc. 15% are over methylated –need folic acid, 45% are undermethylate – need eSam?
- Removal of Toxic Metals & Excess Copper
- MT promotion Supplements.

35. MT promotion therapy
Step 1: Removal of excess copper and toxic metals
- give nutrients which promote MT function
- use clathrating agents – binds copper and nothing else
- Tetrathiolmolydate
- Chelation agents ?
Step 2: Long-term maintenance
- MT promotion formulation (Zinc plus others)
- Minimization of toxic exposures

36. MT Promotion Agents
Primary: Zn, Glutathione, Nacetyl Cysteine, Selenium
Secondary: P-5-P, Vitamins A, C, D, E, Genistein, Biochanin A,
> the Pfieffer Treatment Center is developing & testing supplement combinations and dosages aimed at maximum MT promotion.
Notes: They are going to do studies to determine best protocol.

37. Potential Benefits of MT Promtion therapy
- Reduced tendency for intestinal inflammation, leaky gut, yeast overgrowth, and casein/gluten sensitivity
-Improved hippocampus and amygdala function which may enhance behavior control and learning
- Improved ability to develop new brain cells and neuronal connections
- Protection against future toxic-metal exposures

38. Conclusions
- MT dysfunction may be primary cause of autism
- Autism prevention may be possible by improved prenatal care & early-infant screening for MT dysfunction
- MT promotion therapy is highly promising for autism-spectrum patients

Question from parent about birth control pills.
Answer: Copper overload moms are intolerant to estrogen – no birth control pills.
MT can hold 13 coppers or 7 Zincs

Question: Does use of copper plumbing hurt? What about other environmental damage?
Answer: Bottled water for all autistic patients. In swimming pools – don't use copper sulfate for algae cleaning, there are other things to use.

Question: How long does correction take?
Answer: Takes 60-90 days to correct copper/zinc balance in AD/HD and this may be longer or more involved in autism. Can get bad reaction
in the beginning because the copper is released too fast. Zinc citrate is great. Bioavailable forms – zinc picolinate is good for bad guts, or zinc sulfate. Zinc acetate is good. To determine the Cu/Zn you need to do the plasma cerolum (?) Methylation disorders are easy to diagnose in adults without autism – 75% of undermethylated have seasonal allergies, overmethylated have high food sensitivities.  Hard to diagnose for autistics because they don't verbalize well.

Question: What is a clatherating agent?
Answer: Clatherating agent is something that sort of swallows an atom – not something that binds, but catches the atom in the lattice.
Example: Copper in tetrathiomolybdate

Further information on this research is at the web site:

Protocol for Autism Spectrum:

Submitted by Karen from the autismandenzymes  Yahoo Group.

3: November 26, 2001