Parents as Partners in Autism Research

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Parents as Partners in Autism Research

• A Changing Paradigm

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The Purpose Driven Life

• Never doubt that a small group of thoughtful,
  committed citizens can change the world. Indeed
  its the only thing that ever has. Margaret Mead

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Autism

• Initially thought to be a purely psychiatric
  disorder caused by poor parenting-1950s
• A genetic disorder caused by the unfortunate
  mingling of two individuals who genes resulted in
  autism-1970s
• To a complex interaction of genetic
  susceptibility triggered by an unknown
  environmental insult-1990s

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The Impact of Cyberspace on Autism Research

• Medline discovered by the public in1990s
• Consumers now have access to research that was
  once only available to academic institutions and
  scientists
• Ability to share findings via the internet
• The Autism Community unites with a common goal,
  helping our children

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Parents as Partners in Research

• Parents are the most knowledgable regarding their
  childs medical problems
• Parents have access and are able to utilize
  medical and scientific information now available
  via the internet
• Parents are the stakeholders in the outcome of
  their childs illness and advocates for their
  childs wellness

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How to get started

• Form a close working network with those who share
  your concerns and ideas
• Strategize as to how best advance your ideas and
  initiatives
• Identify effective methods to intervene and
  potential roadblocks
• Periodically reassess your successes and failures
• Never give up!

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The Autism-Mercury ModelMultiple strategies for
affecting change

• Science
• Advocacy
• Policy
• Research

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Science

• Must be able to document that your concerns are
  based in science and valid
• Access to scientific data is essential in
  formulating and supporting your concerns
• Need an effective plan for how to disseminated
  your concerns

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The Autism Mercury Issue

• In 1999 FDA announced infants may have exceeded
  Federal Safety Guidelines for mercury exposure
• A handful of parents nationwide began to suspect
  that thimerosal may be the culprit behind the
  autism epidemic
• They united via the internet and put together a
  comprehensive literature review comparing the
  symptoms of mercury toxicity with those of autism

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Autism-Mercury Hypothesis

• In susceptible infants, prenatal and early
  postnatal exposure to mercury leads to
  neurological damage which results in a spectrum
  of dysfunction ranging from learning
  disabilities, speech and language disorders,
  psychological and behavioral problems, pervasive
  developmental disorders to DSM-IV Autism.

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Support for Hypothesis

• Temporal relationship
• Symptom comparisons
• Toxicity studies
• Genetic susceptibility
• Biochemistry
• Animal models

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Mercury Rising

• In the late 1980s HIB was added to the early
  vaccine schedule, initially administered once at
  18 months.
• Early 1990s Hepatitis B was also added to the
  early infant schedule with the first dose given
  at birth. HIB was also bounced up to 2,4,and 6
  months of age with a booster at 15 mo.
• Early 1990s ACOG also recommended Rho D immune
  globulin with thimerosal be administered to all
  RH- mothers at 28 weeks gestation and
  additionally for any episodes of bleeding or
  invasive procedures.
• CDC recommends for Flu vaccine during pregnancy.

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TOTAL Hg BURDEN AND AUTISM RATES IN CALIFORNIA
1985-98
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SIMILARITIES Include Neurological
Impairment Immune System Dysfunction Abnormal
Biochemistry CNS Structural Abnormalities Neuroc
hemistry Neurophysiology Speech and Language
Impairments Sensory System Abnormalities Motor
System Disorders Psychiatric Disorders
Physical Abnormalities
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Symptom Comparison

• Mercury toxicity manifestations are typically
  delayed for months following the exposure.
• Many parents report a period of normal
  development the first year of life followed by
  regression or a failure to progress.
• Males are more affected/susceptible in both
  disorders, autism and mercury toxicity at a rate
  of approximately 4 to 1.

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Neurological Impairment

• Mercury exposure is known to result in cognitive
  impairment including lower IQs, poor short term,
  auditory and verbal memory, difficulties with
  abstract ideas and complex executive function.
• Autistic children also suffer with cognitive
  impairments, poor memory function and
  difficulties with abstract ideas and
  multi-function commands.

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Immune System Abnormalities

• Immune system dysregulation as evidence by a
  decrease in NK cells and increase in chronicity
  of viral infections.
• A shift from TH1 (viral/fungal killing) to TH2
  (allergy).
• Increased permeability of intestinal epithelium.

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Autoimmunity

• Multiple serum anti-Brain antibodies are present
  in both animals and humans after exposure to
  mercury. These include MBP, NFP and GFP.
• Antibody titers correlated with the degree of
  sensory-motor deficits in workers exposed to
  mercury.
• Numerous studies have documented the presence of
  anti-brain antibodies in children with autism.

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Biochemistry

• Mercury binds SH groups, blocks sulfate
  transport, reduces gluthatione availability and
  glutathione peroxidase and reductase, disrupts
  purine and pyrimidine metabolism and disrupts
  brain mitochondrial activities.
• Autistics are documented to have low sulfate
  levels, low levels of glutathione, abnormal
  glutathione activity in erythrocytes, (purine and
  pyrimidine metabolism errors lead to autism) and
  mitochondrial dysfunction.

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Central Nervous System Structure

• Mercury selectively targets brain areas unable to
  detoxify, accumulates in the amygdala,
  hippocampus, basal ganglia, cerebral cortex,
  damages Purkinje and granule cells in the
  cerebellum, (brain stem defects in some cases)
  causes abnormal cell cytoarchitecture, disrupts
  neuronal migration and maturation, cell
  migration, cell division and progressive
  microcephaly.

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Central Nervous System Structure

• Autism is known to have specific areas of brain
  pathology with many functions spared. Pathology
  in the amygdala, hippocampus, basal ganglia,
  cerebral cortex, damage to Purkinge and granule
  cells in the cerebrum, (brain stem defects in
  some cases) neuronal disorganization, increased
  neuronal cell replication, increased glial cells,
  progressive microcephaly or macrocephaly have all
  been documented in autism.

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Neurochemistry

• Mercury prevents serotonin release and inhibits
  transport, causes calcium disruptions, alters
  dopamine system, peroxidine deficiency in rats,
  elevates epinephrine and norepiephrine, elevates
  glutamate, cortical acetylcholine deficiency,
  increases muscarinic receptor density in the
  hippocampus and cerebellum and causes
  demyelinating neuropathy.

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Neurochemistry

• Autism patients have been found to have decreased
  serotonin synthesis, abnormal calcium metabolism,
  either high or low dopamine levels, elevated
  norepinephrine and epinephrine, elevated
  glutamate and aspartate, cortical acetylcholine
  deficiency, reduced muscarinic receptor binding
  in the hippocampus and demyelination in the brain.

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Neurophysiology

• Autism and mercury toxicity cases reported to
  have abnormal EEGs, epileptiform activity,
  variable patterns including subtle low amplitude
  seizure activity.
• Also abnormal vestibular responses, loss of
  position in space, autonomic disturbances,
  unusual sweating, poor circulation and elevated
  heart rate.

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Speech and Language Deficits

• One of the hallmarks of mercury toxicity is the
  loss of the ability to speak, articulation
  problems and inability to understand speech.
• Documented in numerous studies in adults exposed
  to excessive thimerosal.
• These abnormalities are also a primary feature of
  autism.

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Sensory System Abnormalities

• Abnormal sensations in the mouth and extremities,
  sound sensitivity, abnormal touch sensations,
  touch aversion, over-sensitivity to light, mild
  to profound hearing deficits, and blurred vision
  are all documented to occur in both mercury
  toxicity and autism.

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Motor System Disorders

• Flapping, choreiform movements, circling,
  rocking, toe walking, deficits in hand-eye
  coordination, intention tremors, abnormal gait,
  clumsiness and in-coordination are all documented
  to occur in both mercury poisoning and autism.

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Psychiatric Disturbances

• Repetitive, perseverative and stereotypic
  behaviors, OCD tendencies, depression, mood
  swings, flat affect, impaired face recognition,
  irritability, aggression, temper tantrums,
  anxiety, irrational fears, schizoid tendencies,
  social deficits, shyness and social withdrawal.
  All documented in autism and mercury toxicity
  reports.

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Physical Disturbances

• Hyper or hypotonia, decreased muscle strength
  (especially in the upper body), difficulty
  chewing and swallowing, rashes, dermatitis,
  eczema, diarrhea, abdominal pain, constipation,
  colitis, increased gut permeability and lesions
  of the ileum and colon occur in both autism and
  mercury toxicity cases. (Southby, 1948 and
  Wakefield, 2000)

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Haley Laboratory Toxicity

• In brain homogenates, thimerosal rapidly
  inhibited both tubulin and actin (proteins
  necessary for human neuron growth cone activity)
  more so than equivalent level of mercuric ions
  alone.
• For mammalian enzymes, vaccine solution with
  thimerosal inhibited 95 of M.E. at 5 mcl
  concentrations, whereas minic soln. resulted in
  only a slight inhibition of M.E. at 35 mcl.

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Baskin Toxicological Science

• Incubated human frontal cells with thimerosal.
• Noted DNA damage, nuclear membrane damage,
  caspase 3 activation and apopotic morphology.
• Similar studies by Makani, 2002 found apotosis
  and reduced intracellular glutathione.

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Deth Molecular Psychiatry

• Low concentrations of thimerosal inhibit
  glutathione dependent synthesis of
  methylcobalamin and methionine synthase in human
  neuronal cells.
• Recent investigations have documented striking
  abnormalities in methionine cycle metabolites in
  the plasma of children with autism, indicating
  impaired ability to detoxify metals. (Molecular
  Psych. 2004)
• Additional metal exposure further impairs these
  pathways in a self-reinforcing manner.

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Mercury Blood Levels

• Stajich, et.al. 2000 measured blood mercury
  levels in newborns after administering Hepatitis
  B vaccine containing 12.5 mcg ethyl mercury.
  (Pediatrics, 2000)
• Findings, elevated post immunization mercury
  levels in all neonates studied. Low birth weight
  infants had the highest elevations at 7.36
  mcg/L (- 4.99)
• One infant developed a post vaccine mercury level
  of 23.6 mcg/L. CDC defines a case of mercury
  toxicity as 10 mcg/L

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Pichichero Lancet

• Measured mercury levels in infants after exposure
  to thimerosal containing vaccines.
• Samples drawn after vaccination were drawn at
  convenience.
• Claims the amount of mercury found in the blood
  of infants after exposure to thimerosal
  containing vaccines are below EPA levels of
  concern, giving reassurance about the safety of
  ethyl mercury containing vaccines.

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Pichichero Criticisms

• Blood mercury levels were drawn days to weeks
  after exposure and missed peak levels.
• Mercury exposure levels were ½ what infants
  received in the 1990s.
• According to Halsey had the dose been 62.5mcg and
  draw at peak levels they would have in fact
  exceeded Federal safety guidelines.
• Study size of 33 infants lacks sufficient power
  to establish safety.
• Pichichero acknowledged financial ties to Eli
  Lilly.

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Biochemistry

• Methionine metabolites (methionine, cysteine,
  glutathione) measured in the serum of 20 children
  with autism compared to age matched controls
  revealed severely abnormal profiles.
• Targeted nutritional intervention for three weeks
  with Folinic acid, (800 mcg BID) and Betaine
  (1000 mg. BID) resulted in significant
  improvement in methylation capacity in children
  with autism.
• Micronutrients necessary to support methionine
  synthase include zinc, folinic acid, betaine,
  methyl B-12 and choline. (Jill James, DAN, 2004)

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Animal Model

• Horning, 2004 exposed autoimmune mice to vaccine
  levels of thimerosal.
• The mice exhibited a decrease in weight gain and
  exhibited mutilation behaviors.
• Brain neuropathology identified destruction of
  CA3 hippocampus, increased cell density and
  enlarged brains.

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AdvocacyIdentifying those key to the issue

• Federal Agencies
• Clinicians
• Researchers
• Parents of children exposed to thimerosal

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Advocacy

• Publication of the hypotheses in the journal
  Medical Hypothesis, 2001 and Molecular
  Psychiatry, 2002
• Wide distribution of the paper via private
  meetings with NIH, FDA, CDC, and the Autism
  Community
• Minimal response from Federal Agencies, huge
  response from parents

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Policy

• We took our concerns to Congress
• Govt. Reform Hearing Mercury in Medicine Are
  We Taking Unnecessary Risks? July 18th, 2000
• Petitioned FDA on three separate occasions to
  recall vaccines containing thimerosal
• Educational efforts to inform clinicians and
  consumers to request mercury free vaccines

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Research

• NIH continues to be reluctant to fund
  investigations into thimerosal
• Numerous highly respected researchers have had
  funding denied for grants which included
  thimerosal investigations
• Recent IOM report used as justification for the
  denial of these proposals

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Research by Parents

• Autism A Novel Form of Mercury Poisoning.
  Medical Hypothesis (2001)
• Predicted Mercury Concentrations in Hair From
  Infant Immunizations Cause for Concern.
  Neurotoxicology (2001)
• Toxicology of Neurodevelopmental Disorders The
  role of mercury in the pathogenesis of autism.
  Molecular Psychiatry (2002)
• Reduced Levels of Mercury in First Baby Haircuts
  of Autistic Children. International Journal of
  Toxicology (2003)
• Thimerosal and Autism? A Plausible Hypothesis
  That Should Not Be Dismissed. Medical Hypothesis
  (2004)

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Research Funded by Parents

• SafeMinds has funded over 500,000 in thimerosal
  research over the past 4 years and has over
  250,000 budgeted for 2006
• Previously funded investigations include Dr.Mady
  Hornig, University of Columbia Dr. Richard Deth,
  Northeastern University Dr. Jill James,
  University of Arkansas. Future funding, Dr.
  Thomas Burbacher, University of Washington

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New Directions in Research

• Translational Research Traditional (academic)
  approaches to provide therapies for diseases
  (from bench to bedside) while paying little
  attention to patient-oriented research that
  involves understanding the underlying cause of
  disease and its treatments (from bedside to
  bench).
• Parents are crucial in steering this process

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Parents Leading the Way

• Autism Research Institute
• Autism Society of America
• Cure Autism Now
• National Alliance for Autism Research
• Unlocking Autism

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Growth of the Autism CommunityNew Parents
Leading the Way

• The National Autism Association - Support,
  education and research
• Moms Against Mercury - Advocacy and Education
• Co-Med - FDA petition to remove mercury from
  vaccines
• NoMercury - State and National legislation to
  remove mercury from vaccines
• Generation Rescue - Treatment resources, support
  and education
• A-Champ - Political action committee
• Dads Against Mercury - Advocacy and education
• Autism One - Advocacy, support and education
• Safe Minds - Advocacy and research into mercury
  and autism

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New Directions

• Still a tremendous amount of work needs to be
  done
• Parents bring to the table a wealth of talent,
  time and resources
• We must all work together in a collaborative
  effort in the areas of science, advocacy, policy
  and research
• Add your ideas and support here!