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William J. Walsh, Ph.D.

Pfeiffer Treatment Center
Warrenville, IL
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tpatient medical facility

23,000 patients from all 50 states and 75
foreign co ntries.
Collaboration between medical doctors and
scientists.
Individ alized Biochemical Therapy
Scientific Research
501c3 P blic Charity
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Chemistry Database St dies
Metallothionein Research

idative Damage
-- Essential fats
-- Vasc lar tiss e
-- Imm ne cells (le ocytes)
-- Brain tiss e
Assays of a tism/control brain tiss es.
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10,600 Behavior & ADHD

6,000 A tism
3,700 Schizophrenia & Bipolar
3,600 Depression
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Abo t 90 to 150 assays of chemical

factors in blood, rine, or hair for more
than 6,000 patients

More than 1,000,000 separate chemical

analyses
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Major biochemical abnormalities observed

thro gho t the a tism spectr m.
The biochemical imbalances are more
severe than those for ADHD, violent
behavior, depression, and psychosis.
Female a tistics have more disordered
chemistry than male a tistics.
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Elevated ser m copper

Elevated to
ic metals
Depressed zinc
Undermethylation
Pyrrole disorder
Severe o
idative stress & damage
 

 
 
   

Depressed Methionine and SAMe

Elevated SAH and Adenosine
High Urinary Isoprostanes
Depressed Cysteine and Gl tathione
Low Seleni m Levels
Depressed Cer loplasmin
Elevated Levels of Free-Radicals
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Mean C /Zn Ratio
A tism Spectr m (N=503) 1.63
Controls (N=25) 1.15

t = 8.77 (two-tailed t test); - 

American Psychiatric Association Ann al Meeting

New rleans, 2001.
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1. Depletes metallothionein & gl tathione

2. Associated with inflammation &
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idative stress
3. Can ca se abnormal ne rotransmitter
levels.
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Req ired for development of brain cells,

Primary filter for Hg, Pb, and other metal
to
ics at intestinal and blood/brain barriers,
Req ired for homeostasis of C and Zn,
S pports imm ne f nction.

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Short, dense, ndeveloped brain cells,

Abnormalities observed primarily where MT
levels are highest (amygdala, hippocamp s,
P rinje cells, inferior olives, and pineal
gland).

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MT-3 assists in the pr ning of brain cells,

which maes space for growth of new cells,
MT-1 and MT-2 participate in the nat ral
growth (development) of brain cells,
MT-3 is the primary agent for termination of
growth of f lly-developed brain cells.
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GSH is first line of defense against Hg,

Pb, etc, b t has limited capacity for
to
ic metals.
When > 10% of GSH is bo nd to to
ic
metals, additional to
ics are transferred
from GSH to MT.
Se increases inetics of the GSH/MT
antio
idant system by more than 50%.
For major e
pos res, most to
ic metals
depart the body bo nd to MT.
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Form lation of 22 n trients that promote

genetic e
pression or f nctioning of MT,
incl ding Zinc, Gl tathione, and Seleni m,
Aimed at completion of brain mat ration to
enable gains in cognition, speech, and
socialization,
Has res lted in higher freq ency of a tism
recovery at Pfeiffer Treatment Center.
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P blished in 
 

 
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Walsh, McGinnis, and Yao.

Findings: Elevated o
idative damage to fats

and vasc lar tiss es for a tistic s bjects,
compared to controls.
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Untreated a tism may be ne rodegenerative

with o
idative damage ca sing slow, grad al
loss of brain cells and IQ.

Antio
idant therapy may be necessary

thro gho t the life of a person diagnosed
with an a tism spectr m disorder.
  
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Most yo ng ASD patients appear q ite bright

Many s ccessf lly treated children become

mainstreamed and academic leaders,

Most ad lt a tistics e
hibit mental severe

retardation.
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SAMe levels 36% lower,

SAMe/SAH ratios 50% lower,
Homocysteine 180% higher,
Cysteine 40% lower,
GSH 25-60% lower.
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W.McGinnis, T.A dhya, W.Walsh, J.Jacson,
J.McLaren-Howard, A.Lewis, P.La da, D.Bib s,
F.J rna, R.Lietha, A.Hoffer.

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Do ble blind, controlled st dy,

176 brain tiss es & 22 peripheral samples
from U. of Marylands A tism Brain Ban,
Elemental analysis for 16 elements, incl ding
Hg, Pb, C , Zn, and Se sing high-brilliance
photons at ANLs Advanced Photon So rce),
First elemental assays ever attempted for
a tism & control brain tiss es.

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Cerebell m
S perior Corte

Deep Corte

White Matter

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Abnormal levels of Ca, S, Fe, Zn in a tism brains,

The abnormalities are striingly different for male

and female a tistics, s ggesting that male and
female a tism may have different genetic origins.

Merc ry not detected (detection limit of abo t 100

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Strong genetic predisposition

nset after environmental ins lt
High o
idative stress
Undermethylation
Incomplete brain mat ration
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-- Higher concordance in siblings
-- 60 to 80% concordance in identical twins
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-- Identical twin concordance not 100%
-- Major differences in many identical twins.
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The genetic defect involves a
weaened ability to cope with
environmental stresses
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A tism evident at birth. Greater severity of
symptoms. Mental retardation often present.

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Regressive a tism. Symptoms depend on
developmental stage d ring ins lt.
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C rrent consens s that a tism res lts from

many genetic defects, rather than from a
single gene.

A common factor in these genetic defects

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Genetic tendency for depressed GSH, MT,

Se, etc at intestinal and blood/brain barriers,
Inability to prevent Hg, Pb, Cd, and reactive
o
ygen specie from invading the brain.
-- destr ction of brain cells
-- interr ption of brain mat ration process
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Hypersensitivity to Hg and other to
ic metals

Hypersensitivity to certain proteins (casein,
gl ten, etc)
Poor imm ne f nction
Disr ption of the methylation cycle
Inflammation of the brain & G.I. tract.
Depletion of gl tathione & metallothionein
E
cessive amo nts of nbo nd copper
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Destroys digestive enzymes needed to brea
down casein & gl ten proteins,
Promotes candida/yeast levels,
Diminishes Zn levels and prod ction of
stomach acid,
Prod ces inflammation,
Ineffective barrier to to
ic metals at the
intestinal m cosa.
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1. Chelation with DMSA, DMPS, EDTA, etc.

2. Methyl B-12
3. Metallothionein Promotion
4. Transdermal or Injected Gl tathione
5. Zn, Se, CoQ-10, Ta rine, Vitamins A,C,D,E
6. Alpha Lipoic Acid
7. Risperdal
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What % of a tism cases are triggered by Hg?

Can old Hg stay in the brain and ca se
contin ing damage?
How serio s is the contin ing daily e
pos re
to Hg from the environment?
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DMSA and DMPS are powerf l antio
idants.

Chelation can provide antio
idant benefits
even if to
ic metals are  present.
For many patients, the primary benefits of
chelation res lt from antio
idant properties,
and not from removal of Hg or other metals.
Antio
idant benefits from chelation appear to
fade away after abo t 2-4 wees.
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Rapid removal of to
ic metals from

peripheral soft tiss es & blood, th s
preventing their access to the brain,

Powerf l antio
idant
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Does not fi
intestinal or blood/brain barriers,

rendering the patient v lnerable to f t re
to
ic e
pos res,
Antio
idant benefits are temporary, lasting
only 2-4 wees,
May not remove to
ic metals from the brain,
Complicates Zn management.
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Identification & individ alized treatment of
biochemical imbalances,
MT-Promotion therapy,
Selective se of adj nct therapies
- CF/GF diet
- Normalization of intestinal flora
- Methylation therapies
- Digestive enzymes
- etc.
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Advances in cognition, socialization,
and speech by enhanced development
of immat re brain cells and new
synaptic connections.
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Elimination of to
ic metals & e
cess C
Improved imm ne f nction
Healing of the G.I. tract
Red ced food sensitivities
Improved behavior control
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Genero s amo nts of Zn and GSH which are
essential to ind ction and f nctioning of MT,
Seleni m, Vitamins B-6, C, E, which are
nown to promote MT,
S pplements of the 14 amino-acid
constit ents of MT in the proportion they
e
ist in MT proteins.
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Directly aimed at development of brain cells

& new synaptic connections,
Potential for permanently correcting the
intestinal and blood/brain barriers,
Restores the nat ral (and powerf l) body
system for coping with to
ic metals,
Potential for eliminating food sensitivities,
yeast problems & intestinal inflammation.
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Pre-loading with zinc is necessary to prevent

temporary side effects,
B ilding p tolerance to the MT Promoter
form lation can be a slow process for some
children,
Commercial lab testing to determine MT
stat s is in its infancy.
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Elimination of to
ic metals and e
cessive

o
idative stress,
Behavioral therapy to stim late development
of brain cells and synaptic connections,
MT-Promotion therapy to enable completion
of brain mat ration.
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idative stress may be the decisive factor in

a tism-spectr m disorders.
Treatment protocols aimed at (1) red ction of
o
idative stresses and (2) development of
new brain cells and synapses are highly
promising.
Long-term antio
idant therapy may be
needed to prevent loss of brain cells and
mental retardation.
&@M+E

William J. Walsh, Ph.D.

Pfeiffer Treatment Center
Warrenville, Illinois
www.hriptc.org