Incomplete Brain Development in Autism: Causes and Treatment - PowerPoint PPT Presentation

1 / 58
About This Presentation
Title:

Incomplete Brain Development in Autism: Causes and Treatment

Description:

Alpha Lipoic Acid. Risperdal. Mercury Questions. What % of autism cases are triggered by Hg? ... Supplements of the 14 amino-acid constituents of MT in the ... – PowerPoint PPT presentation

Number of Views:275
Avg rating:3.0/5.0
Slides: 59
Provided by: patm165
Category:

less

Transcript and Presenter's Notes

Title: Incomplete Brain Development in Autism: Causes and Treatment


1
Incomplete Brain Development in Autism Causes
and Treatment
  • William J. Walsh, Ph.D.
  • Pfeiffer Treatment Center
  • Warrenville, IL

2
Pfeiffer Treatment Center
  • Outpatient medical facility
  • 23,000 patients from all 50 states and 75 foreign
    countries.
  • Collaboration between medical doctors and
    scientists.
  • Individualized Biochemical Therapy
  • Scientific Research
  • 501c3 Public Charity

3
Pfeiffer Autism Research
  • Chemistry Database Studies
  • Metallothionein Research
  • Oxidative Damage
  • -- Essential fats
  • -- Vascular tissue
  • -- Immune cells (leukocytes)
  • -- Brain tissue
  • Assays of autism/control brain tissues.

4
Pfeiffer Chemistry Database
  • 10,600 Behavior ADHD
  • 6,000 Autism
  • 3,700 Schizophrenia Bipolar
  • 3,600 Depression

5
Pfeiffer Autism Database
  • About 90 to 150 assays of chemical factors in
    blood, urine, or hair for more than 6,000
    patients
  • More than 1,000,000 separate chemical analyses

6
Year 1999 Discovery
  • Undermethylation
  • Present in more than 90 of
  • autism-spectrum children.

7
Year 2000 Discovery
  • Greater than 99 of ASD patients exhibit abnormal
    Cu and Zn levels in blood.
  • Normally, Cu Zn are homeostatically controlled
    by metallothionein proteins.
  • Conclusion Depressed metallothionein
    activity is a distinctive feature of autism.

8
Autism Database Analysis
  • Major biochemical abnormalities observed
    throughout the autism spectrum.
  • The biochemical imbalances are more severe than
    those for ADHD, violent behavior, depression, and
    psychosis.
  • Female autistics have more disordered chemistry
    than male autistics.

9
High Incidence Biochemical Abnormalities in Autism
  • Elevated serum copper
  • Elevated toxic metals
  • Depressed zinc
  • Undermethylation
  • Pyrrole disorder
  • Severe oxidative stress damage

10
Biochemical Abnormalities in Autism ---
Continued ---
  • Depressed Methionine and SAMe
  • Elevated SAH and Adenosine
  • High Urinary Isoprostanes
  • Depressed Cysteine and Glutathione
  • Low Selenium Levels
  • Depressed Ceruloplasmin
  • Elevated Levels of Free-Radicals

11
Each of the Biochemical Abnormalities Are
Associated With Oxidative Stress
  • Conclusion Autism is a condition of oxidative
    stress
  • An oxidative stress model can explain most
    symptoms of autism
  • Oxidative stress has become a leading focus of
    autism research.

12
Experimental Results and Statistical Analysis
  • Mean Cu/Zn Ratio
  • Autism Spectrum (N503) 1.63
  • Controls (N25)
    1.15
  • t 8.77 (two-tailed t test) p lt 0.0001
  • American Psychiatric Association Annual Meeting
  • New Orleans, 2001.

13
Insufficient Ceruloplasmin Levels in
Autistic-Spectrum Patients

  • Autistics Controls
  • Unbound Serum Cu 41 21
  • Not bound to ceruloplasmin
  • P lt 0.01
  • Conclusion Autistics exhibit excessive levels
    of loosely bound or free-radical copper (high
    oxidative stress).

14
Abnormally Elevated Copper
  • Depletes metallothionein glutathione
  • Associated with inflammation excessive
    oxidative stress
  • Can cause abnormal neurotransmitter levels.

15
Low Metallothionein Levels in Autismp lt 0.0092
16
Why is Metallothionein Important?
  • Required for development of brain cells,
  • Primary filter for Hg, Pb, and other metal
    toxics at intestinal and blood/brain barriers,
  • Required for homeostasis of Cu and Zn,
  • Supports immune function.
  • -- MT is a magnet for mercury, but MT activity
    is weak in autism-spectrum children.

17
Autopsy Studies Show Structural Abnormalities in
Autistic Brains
  • Short, dense, undeveloped brain cells,
  • Abnormalities observed primarily where MT levels
    are highest (amygdala, hippocampus, Purkinje
    cells, inferior olives, and pineal gland).
  • Conclusion Incomplete maturation of autistic
    brains may be due to low MT levels.

18
The Role of Metallothionein in the Development of
Brain Cells
  • MT-3 assists in the pruning of brain cells, which
    makes space for growth of new cells,
  • MT-1 and MT-2 participate in the natural growth
    (development) of brain cells,
  • MT-3 is the primary agent for termination of
    growth of fully-developed brain cells.

19
Teamwork Between MT, GSH, SeThe Three
Musketeers
  • GSH is first line of defense against Hg, Pb, etc,
    but has limited capacity for toxic metals.
  • When gt 10 of GSH is bound to toxic metals,
    additional toxics are transferred from GSH to MT.
  • Se increases kinetics of the GSH/MT antioxidant
    system by more than 50.
  • For major exposures, most toxic metals depart the
    body bound to MT.

20
MT-Promotion Therapy
  • Formulation of 22 nutrients that promote genetic
    expression or functioning of MT, including Zinc,
    Glutathione, and Selenium,
  • Aimed at completion of brain maturation to enable
    gains in cognition, speech, and socialization,
  • Has resulted in higher frequency of autism
    recovery at Pfeiffer Treatment Center.
  • U.S. Patent 7,232,575 (issued June, 2007)

21
Oxidative Damage Study 1
  • Published in October, 2006. Archives of
    Neurology Vol. 631161-1164. Authors Pratico,
    Walsh, McGinnis, and Yao.
  • Findings Elevated oxidative damage to fats and
    vascular tissues for autistic subjects, compared
    to controls.

22
Higher iP Levels in Autismp lt 0.01
23
Oxidative Damage Study 2
  • American Journal of Biotechnology and
    Biochemistry 4(2)61-72, 2008. Authors Evans,
    McGinnis, Walsh, Perry, Salomon, Lewis, et. al.
  • First direct evidence of oxidative damage in the
    autistic brain.
  • Evidence of neurodegeneration in autism

24
Implications of Oxidative Damage Studies
  • Untreated autism may be neurodegenerative with
    oxidative damage causing slow, gradual loss of
    brain cells and IQ.
  • Antioxidant therapy may be necessary throughout
    the life of a person diagnosed with an autism
    spectrum disorder.

25
Clinical Evidence (n7,000) of Neurodegeneration
in Autism
  • Most young ASD patients appear quite bright
  • Many successfully treated children become
    mainstreamed and academic leaders,
  • Most adult autistics exhibit mental severe
    retardation.

26
Leukocyte Study
  • Altered Sulfur Amino Acid Metabolism in
    Immune Cells of Children Diagnosed with Autism
    J. Suh, W. Walsh, W. McGinnis, A. Lewis, and B.
    Ames.
  • American Journal of Biochemistry
    Biotechnology 4 (2) 105-113, 2008.

27
Leukocyte Findings for ASD
  • SAMe levels 36 lower,
  • SAMe/SAH ratios 50 lower,
  • Homocysteine 180 higher,
  • Cysteine 40 lower,
  • GSH 25-60 lower.

28
Leukocyte Study Conclusion
  • Evidence of increased inflammation, increased
    oxidative stress, and depressed immune function
    in autism.

29
Urine Pyrroles and Autism
  • Discerning the Mauve Factor, Part 1, 2.
    Alternative Therapies in Health and Medicine,
    Vol. 14, No. 2, March, 2008.
  • W.McGinnis, T.Audhya, W.Walsh, J.Jackson,
    J.McLaren-Howard, A.Lewis, P.Lauda, D.Bibus,
    F.Jurnak, R.Lietha, A.Hoffer.
  • 25-35 of ASD patients exhibit elevated pyrroles.
  • Urine HPL is a good marker for oxidative stress.

30
Correlation of iP vs. Kp(corrected for creatinine)
31
(No Transcript)
32
Comparison of Elemental Levels in Autism
Control Brains
  • Double blind, controlled study,
  • 176 brain tissues 22 peripheral samples from U.
    of Marylands Autism Brain Bank,
  • Elemental analysis for 16 elements, including Hg,
    Pb, Cu, Zn, and Se using high-brilliance photons
    at ANLs Advanced Photon Source),
  • First elemental assays ever attempted for autism
    control brain tissues.

33
Brain Regions Studied
  • Cerebellum
  • Superior Cortex
  • Deep Cortex
  • White Matter
  • Note 20 autistic 20 control tissue samples
  • from each brain region

34
Autism/Control Tissue Array
35
Summary of Findings
  • Abnormal levels of Ca, S, Fe, Zn in autism
    brains,
  • The abnormalities are strikingly different for
    male and female autistics, suggesting that male
    and female autism may have different genetic
    origins.
  • Mercury not detected (detection limit of about
    100 ppb)
  • Note Article prepared for Neurology.

36
Distinctive Features of Autism
  • Strong genetic predisposition
  • Onset after environmental insult
  • High oxidative stress
  • Undermethylation
  • Incomplete brain maturation

37
Genetic Aspects of Autism
  • Strong genetic predisposition
  • -- Higher concordance in siblings
  • -- 60 to 80 concordance in identical twins
  • Influence of environmental factors
  • -- Identical twin concordance not 100
  • -- Major differences in many identical twins.

38
QUESTION How Can There Be An Epidemic of a
Genetic Condition?
  • ANSWER
  • The genetic defect involves a weakened ability
    to cope with environmental stresses

39
Timing of Environmental Insults is 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.

40
Severity of Environmental Insult Is Important
  • Example Disruption of key brain proteins
  • during development of speech
    center.
  • Mild insult results in speech delay.
  • Severe insult results in mutism.

41
Poly-Gene Nature of Autism
  • Current consensus that autism results from many
    genetic defects, rather than from a single gene.
  • A common factor in these genetic defects may be
    diminished ability to cope with oxidative stress.

42
What is Autism?Oxidative Stress Theory of Autism
  • Genetic tendency for depressed GSH, MT, Se, etc
    at intestinal and blood/brain barriers,
  • Inability to prevent Hg, Pb, Cd, and reactive
    oxygen specie from invading the brain.
  • -- destruction of brain cells
  • -- interruption of brain maturation
    process

43
Consequences of Oxidative Stress Mirror Classic
Symptoms of Autism
  • Hypersensitivity to Hg and other toxic metals
  • Hypersensitivity to certain proteins (casein,
    gluten, etc)
  • Poor immune function
  • Disruption of the methylation cycle
  • Inflammation of the brain G.I. tract.
  • Depletion of glutathione metallothionein
  • Excessive amounts of unbound copper

44
Consequences of Oxidative Stress in the G.I. Tract
  • Destroys digestive enzymes needed to break down
    casein gluten proteins,
  • Promotes candida/yeast levels,
  • Diminishes Zn levels and production of stomach
    acid,
  • Produces inflammation,
  • Ineffective barrier to toxic metals at the
    intestinal mucosa.

45
Most Popular Autism Therapies Enhance Antioxidant
Protection
  • Chelation with DMSA, DMPS, EDTA, etc.
  • Methyl B-12
  • Metallothionein Promotion
  • Transdermal or Injected Glutathione
  • Zn, Se, CoQ-10, Taurine, Vitamins A,C,D,E
  • Alpha Lipoic Acid
  • Risperdal

46
Mercury Questions
  • What of autism cases are triggered by Hg?
  • Can old Hg stay in the brain and cause
    continuing damage?
  • How serious is the continuing daily exposure to
    Hg from the environment?

47
Chelation and Oxidative Stress
  • DMSA and DMPS are powerful antioxidants.
  • Chelation can provide antioxidant benefits even
    if toxic metals are not present.
  • For many patients, the primary benefits of
    chelation result from antioxidant properties, and
    not from removal of Hg or other metals.
  • Antioxidant benefits from chelation appear to
    fade away after about 2-4 weeks.

48
Primary Benefits of Chelation
  • Rapid removal of toxic metals from peripheral
    soft tissues blood, thus preventing their
    access to the brain,
  • Powerful antioxidant

49
Limitations of Chelation
  • Does not fix intestinal or blood/brain barriers,
    rendering the patient vulnerable to future toxic
    exposures,
  • Antioxidant benefits are temporary, lasting only
    2-4 weeks,
  • May not remove toxic metals from the brain,
  • Complicates Zn management.

50
Pfeiffer Treatment Protocol
  • Identification individualized treatment of
    biochemical imbalances,
  • MT-Promotion therapy,
  • Selective use of adjunct therapies
  • - CF/GF diet
  • - Normalization of intestinal flora
  • - Methylation therapies
  • - Digestive enzymes
  • - etc.

51
MT Promotion Therapy
  • Primary Objective
  • Advances in cognition, socialization, and
    speech by enhanced development of immature brain
    cells and new synaptic connections.

52
MT Promotion Therapy
  • Secondary Objectives
  • Elimination of toxic metals excess Cu
  • Improved immune function
  • Healing of the G.I. tract
  • Reduced food sensitivities
  • Improved behavior control

53
MT-Promotion Formulation
  • Generous amounts of Zn and GSH which are
    essential to induction and functioning of MT,
  • Selenium, Vitamins B-6, C, E, which are known
    to promote MT,
  • Supplements of the 14 amino-acid constituents of
    MT in the proportion they exist in MT proteins.

54
Unique Advantages of MT-Promotion
  • Directly aimed at development of brain cells
    new synaptic connections,
  • Potential for permanently correcting the
    intestinal and blood/brain barriers,
  • Restores the natural (and powerful) body system
    for coping with toxic metals,
  • Potential for eliminating food sensitivities,
    yeast problems intestinal inflammation.

55
MT Promotion Challenges
  • Pre-loading with zinc is necessary to prevent
    temporary side effects,
  • Building up tolerance to the MT Promoter
    formulation can be a slow process for some
    children,
  • Commercial lab testing to determine MT status is
    in its infancy.

56
A Roadmap for Enhanced Cognition, Speech, and
Socialization
  • Elimination of toxic metals and excessive
    oxidative stress,
  • Behavioral therapy to stimulate development of
    brain cells and synaptic connections,
  • MT-Promotion therapy to enable completion of
    brain maturation.

57
Summary
  • Oxidative stress may be the decisive factor in
    autism-spectrum disorders.
  • Treatment protocols aimed at (1) reduction of
    oxidative stresses and (2) development of new
    brain cells and synapses are highly promising.
  • Long-term antioxidant therapy may be needed to
    prevent loss of brain cells and mental
    retardation.

58
THANK YOU!
  • William J. Walsh, Ph.D.
  • Pfeiffer Treatment Center
  • Warrenville, Illinois
  • www.hriptc.org
Write a Comment
User Comments (0)
About PowerShow.com