Download IMFAR Meeting – London – May, 2008

ENVIRONMENTAL PATHWAYS
TO AUTISM SPECTRUM
DISORDERS
Research Opportunities & Current
US Government Studies
“The Search for Causes and Cures”
Presentation by David Kirby
Briefing by Reps. Maloney & Smith
Capitol Hill, Washington, DC- July 17, 2009
1
The Coming “Tidal Wave”
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U.C. M.I.N.D. Institute: 600-700% rise in CA cases since 1990: cannot be
explained by changes in Dx or counting. "It's time to start looking for
the environmental culprits” -- Dr. Irva Hertz-Picciotto, UC Davis.
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Sacramento Bee: 6,300 CA adults get ASD services. In four years, it will
almost double to 11,000. By 2018 it will triple to 19,000. “A tidal wave of
ASD youngsters is moving toward adulthood.”
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Orange Co. Schools: “If increase is better diagnosis, both Elementary
and High Schools should have similar rates. But the HS district is
setting up more self-contained classrooms to accommodate the influx
this coming year.” (Why so many more 9th graders than 10th graders?).
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US CDC: Autism rate among 8-year-olds in 2000: 1-in 166; In 2002: 1-in150; In 2004: ?? (FOIA Pending) We still do not know the rate among
children born in 1996 and after.
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A NEW AUTISM VOCABULARY
Cause, Effect & Connections of:
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Immune Hyper-activation/Suppression/Autoimmunity
Oxidative Stress
Neuro-inflammation
Glutathione Depletion
Metal Metabolism Disorder
Myelin Disorders
Mitochondrial Dysfunction
Activation of Microglial cells/“Gliosis”
Cytokine Imbalances
Methionine Cycle Disruption/Impaired Methylation
Vitamin D Deficiency
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Calcium Channeling Imbalances (CACNA-1G?)
Vaccines & Autism: Asked and Answered?
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Only one vaccine (MMR) and one component
(Thimerosal) have been studied.
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Almost all were epidemiological studies, many with
serious flaws and limitations.
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Thimerosal was reduced in 2002-03 – these children
are not 8 years old yet; flu shot raised exposures
since.
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Early intervention can “artificially” boost ASD rates
among 3-year-olds by 75% (CDC study).
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METALS
Organic Mercury
Inorganic Mercury
Aluminum
Arsenic
Antimony – flame retardants
Lead/Tin/Cadmium etc.
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GLUTATHIONE:
Sulfur-based protein that binds with heavy metals,
viruses and toxins to eliminate them from system.
Very powerful fighter against oxidative stress.
Critical for protecting mitochondrial membranes
from permeation/damage caused by toxins.
Tylenol blocks glutathione production in the liver.
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ASD kids have low or depleted levels of “thiols,” including
glutathione.
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Thiols are mercaptans, Latin for “capturing mercury.”
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Targeted nutritional intervention with Folinic acid, and
Betaine resulted in significant improvement in ASD children.
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Addition of methyl B-12 to “cocktail” brought all ASD children
within normal “thiol” levels, such as glutathione.
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Thimerosal damage to nerves was associated with glutathione
depletion, protection was restored with glutathione precursors.
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“Changes in astrocytes and microglia in primate
brains after long-term methylmercury exposure.”
Neurotoxicology. 1996;17:127-138.
Burbacher: Inorganic Hg, presumably from methyl Hg,
continued to increase throughout all exposure durations.
Both astrocyte and microglial cells had “substantially
elevated” inorganic mercury deposits.
“Inorganic Hg in the brain may be a toxic form responsible
for activation of astrocyte and microglia.”
Activation of astrocyte and microglial cells was not noted
for six months or more, in some cases.
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HARVARD:
“Large Brains in Autism: The Challenge of
Pervasive Abnormality”
The Neuroscientist, Volume 11, Number 5, 2000
Neuro-inflammation, oxidative stress &
microglia damage found in autistic brain tissue.
“Chronic disease or external environmental
sources” (ie, heavy metals) may be the cause.
“Oxidative stress, brain inflammation, and
microgliosis has been much documented in
association with heavy metal exposures.”
9
CDC -VSD: Thimerosal and
Neurodevelopmental Disorders
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UNIV of TEXAS - 2005: “HIGHER RISK OF AUTISM NEAR
COAL-FIRED PLANTS” - Health & Place - 12 (2006) 203-209
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Study looked at Texas county levels of emissions, compared
to ASD rates and special ed in 1,200 school districts.
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Autism increased as mercury emissions rose. For every
thousand pounds of Hg, there was a 61 percent increase in
autism rates.
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One county with low mercury emissions but significant
autism rates was found to harbor one of the nation’s largest
mercury mines.
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“A potentially important connection between environmental
exposure to mercury and the development of autism.”
11
Myelin:
“A white fatty substance that
forms a sheath around nerve fibers
to provide electrical insulation”
12
The Bailey Banks Case
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Court ruled MMR vaccine produced acute disseminated
encephalomyelitis (ADEM) – Inflammation of brain and
spinal cord and damage to the myelin sheath.
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ADEM can be caused by natural infections, especially
measles virus. But is also a post-vaccine injury, especially
rabies, pertussis, influenza, and MMR.
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1994 IOM: Biologically plausible for a vaccine to
“induce...an autoimmune response...by nonspecific
activation of the T cells directed against myelin proteins.”
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Symptoms: headache, delirium, lethargy, seizures, stiff
neck, fever, ataxia (incoordination), nausea, vomiting,
weight loss, irritability, changes in mental status.
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Banks Cont’d
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Bailey had MRI 16 days after MMR vaccine, confirmed
his diagnosis. Most given Tylenol and sent home.
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Tylenol can affect glutathione, mitochondrial function
and oxidative stress.
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A small study at UCSD showed kids given Tylenol after
MMR were several times more likely to develop ASD.
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"Tylenol and MMR was significantly associated with
autistic disorder," the authors wrote.
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Banks
“Bailey’s ADEM was severe enough to
cause lasting, residual damage, and retarded
his developmental progress, which fits under
the generalized heading of PDD-(NOS).”
“Bailey would not have suffered this delay
but for the administration of MMR.
“A proximate sequence of cause and effect
leading inexorably from vaccination to
PDD.”
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HepB, Myelin and MS
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Vaccine Court – 65 HepB-Demyelinating Cases.
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Sample case: Court ruled adult female contracted a
demyelinating disease and MS, and eventually died,
after receiving the Hepatitis B vaccine series.
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Just the most recent case in a rash of rulings on
HepB and “demyelinating diseases such as
transverse myelitis (TM), Guillain-Barré syndrome
(GBS), chronic inflammatory demyelinating disease
(CIDP), and multiple sclerosis (MS).”
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HepB and Myelin in Infants
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Oct. 2008 issue of Neurology - Hep B vaccine in
infants associated with a 50% increased risk for
CNS inflammatory demyelination.
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Especially true for GSK’s Engerix B vaccine - Risk
was 74%. Among ASD children with MS it
increased 177%
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“The Engerix B vaccine appears to increase this
risk, particularly for confirmed multiple sclerosis,
in the longer term.
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Mitochondria:
“Powerhouse of the cell that converts
food and oxygen into energy”
Mitochondrial Dysfunction:
Low cellular energy caused by genes or
environmental factors such as metals
and drugs, including antidepressants
and Tylenol
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Hannah Poling Concession
November 9, 2007
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Hannah met all milestones in first 18 months. At 9 months:
Mimicking sounds, crawling, and sitting.
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At 12-month pediatric visit: Saying “Mom” & “Dad,”
pulling self up, cruising.
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July 19, 2000 visit - Hannah “spoke well” was “alert and
active,” with regular bowel movements and good sleeping
habits.
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July 19, 2000 visit – Hannah received 9 vaccines:
D-T-aP, M-M-R, Hib, Varivax, and Polio
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Followed by fevers, rashes, and descent into ASD.
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Poling Concession #2
February 21, 2008
Amended report from Dr. Zimmerman:
“The cause for regressive encephalopathy at age 19
months was underlying mitochondrial dysfunction,
exacerbated by vaccine-induced fever and immune
stimulation that exceeded metabolic reserves.”
Epilepsy was “part of the same pathogenesis that led
to autistic encephalopathy.”
SHORT VERSION: Hannah’s autism was caused by
a vaccine-induced exacerbation of her underlying
mitochondrial dysfunction.
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“Bridging from Cells to Cognition in Autism: Pathways
to Defective Brain Function and Plasticity”
Dr. Martha Herbert, Harvard – Am. Journ. Biochem. & Biotech 4 (2): 167-176, 2008
Autism may begin when an early environmental, infectious,
seizure, or autoimmune insult triggers an immune response.
This response increases oxidative stress in the brain.
Oxidative stress leads to DNA damage (nuclear and
mitochondrial) and metabolic (glutathione) enzyme blockage.
Inflammatory and oxidative stressors persist beyond early
development, producing ongoing functional consequences.
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“Bridging from Cells to Cognition in Autism:
Pathways to Defective Brain Function and Plasticity”
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In the central nervous system, continued use of damaged
mitochondria and impaired metabolic function may
generate additional oxidative stress.
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This oxidative stress causes further activation of the
immune system, leading to even more oxidative stress.
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Such a mechanism would self-sustain and possibly
progressively worsen.
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Mitochondrial dysfunction found in autism would activate
both astroglia and microglia. These activated cells can then
initiate a broad-spectrum pro-inflammatory gene response.
22
Seven Studies to Watch
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1) Unanimous endorsement by the National Vaccine Advisory Committee to look at
the feasibility of a large vaccinated-unvaccinated study, with autism as an outcome.
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2) NVAC endorsement of vaccine-autism investigations into children with
mitochondrial dysfunction.
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3) NVAC endorsement of vaccine-autism investigations into children with
regressive form of ASD (15-55%).
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4) NVAC endorsement of investigations into vaccine injuries such as encephalitis,
seizure disorders and demyelinating diseases at risk factors for ASD.
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5) NIH Early Autism Risk Longitudinal Investigations EARLI study which will
follow 1,200 pregnant mothers with one ASD child, looking at all environmental
triggers, including metals, thimerosal and vaccines.
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6) HHS/EPA National Children’s Study, which will follow 100,000 children and look
at all environmental factors and outcomes, including metals, vaccines and ASD.
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7) CDCs Centers for Autism and Developmental Disabilities Research and
Epidemiology (CADDRE) Network, to study, "mercury exposures, including any
vaccine use by the mother during pregnancy and the child's vaccine exposures.”
23
ASD and Mitochondria –
PloS Online – 12/08
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Scientists at Cleveland Clinic, Harvard and Johns
Hopkins: "There might be no difference between
the inflammatory or catabolic stress of vaccinations
and that of common childhood diseases.”
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"Large, population-based studies will be needed to
identify a possible relationship of vaccination with
autistic regression in persons with mitochondrial
cytopathies."
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Dr. Duane Alexander - NICHD
“Important to ask if some children are more
susceptible to some vaccine characteristic or
component, and may develop an ASD in
response.”
There may be "subpopulations unable to
remove mercury from the body as fast as others,
or some adverse or cross-reacting response to a
vaccine component, or a mitochondrial disorder
increasing the adverse response to vaccineassociated fever.”
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Dr. Anthony Fauci - NIAID
"If we can show that individuals of a certain
genetic profile have a greater propensity for
developing adverse events, we may want to
screen everyone prior to vaccination."
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The “1322 Project”
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Announced at Autism One - Expert legal review of previous
Vaccine Court decisions to determine ASD prevalence.
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Preliminary results show ASD rate many times higher than 1-in150. Final results to be announced soon.
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CBS Evening News: At least 1322 cases paid out for vaccineinduced brain damage, encephalopathy and/or seizure
disorders.
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“There may be cases involving autistic-like disorders which
manifested following a Vaccine Injury Table injury. Any residual
effects thereof would be presumed to be vaccine-caused. Autism
cases involving Table Injuries have been compensated.”
– Gary J. Golkiewicz, Vaccine Court Chief Special Master
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