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ENVIRONMENTAL PATHWAYS ENVIRONMENTAL PATHWAYS TO AUTISM SPECTRUM TO AUTISM SPECTRUM

DISORDERS DISORDERS

Research Opportunities & Research Opportunities & Current US Government Current US Government

StudiesStudies““The Search for Causes and Cures”The Search for Causes and Cures”

PPresentation by David Kirbyresentation by David KirbyBriefing by Reps. Maloney & SmithBriefing by Reps. Maloney & Smith

Capitol Hill, Washington, DC- July 17, Capitol Hill, Washington, DC- July 17, 20092009

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The Coming “Tidal Wave”The Coming “Tidal Wave” U.C. M.I.N.D. Institute:U.C. M.I.N.D. Institute: 600-700% rise in CA cases since 1990: 600-700% rise in CA cases since 1990:

cannot be explained by changes in Dx or counting. cannot be explained by changes in Dx or counting. "It's time to "It's time to start looking for the environmental culprits” -- Dr. Irva Hertz-start looking for the environmental culprits” -- Dr. Irva Hertz-Picciotto, UC Davis. Picciotto, UC Davis.

Sacramento Bee:Sacramento Bee: 6,300 CA adults get ASD services. In four 6,300 CA adults get ASD services. In four years, it will almost double to 11,000. By 2018 it will triple to 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 19,000. “A tidal wave of ASD youngsters is moving toward adulthood.”adulthood.”

Orange Co. Schools:Orange Co. Schools: “If increase is better diagnosis, both “If increase is better diagnosis, both Elementary and High Schools should have similar rates. But Elementary and High Schools should have similar rates. But the HS district is setting up more self-contained classrooms to the HS district is setting up more self-contained classrooms to accommodate the influx this coming year.” (Why so many more accommodate the influx this coming year.” (Why so many more 99thth graders than 10 graders than 10thth graders?). graders?).

US CDC:US CDC: Autism rate among 8-year-olds in 2000: Autism rate among 8-year-olds in 2000: 1-in 1661-in 166; In ; In 2002: 2002: 1-in-1501-in-150; In 2004: ?? (; In 2004: ?? (FOIA PendingFOIA Pending) We ) We stillstill do not do not know the rate among children born in 1996 and after.know the rate among children born in 1996 and after.

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A NEW AUTISM VOCABULARYA NEW AUTISM VOCABULARYCause, Effect & Connections of:Cause, Effect & Connections of:

Immune Immune Hyper-activation/Suppression/AutoimmunityHyper-activation/Suppression/Autoimmunity

Oxidative StressOxidative Stress Neuro-inflammation Neuro-inflammation Glutathione DepletionGlutathione Depletion MetalMetal Metabolism Disorder Metabolism Disorder MyelinMyelin Disorders Disorders MitochondrialMitochondrial Dysfunction Dysfunction Activation of Microglial cells/“Gliosis”Activation of Microglial cells/“Gliosis” Cytokine Imbalances Cytokine Imbalances Methionine Cycle Disruption/Impaired Methionine Cycle Disruption/Impaired

MethylationMethylation Vitamin D DeficiencyVitamin D Deficiency Calcium Channeling Imbalances (CACNA-1G?)Calcium Channeling Imbalances (CACNA-1G?)

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Vaccines & Autism: Asked and Vaccines & Autism: Asked and Answered?Answered?

Only one vaccine (Only one vaccine (MMRMMR) and one ) and one component (component (ThimerosalThimerosal) have been ) have been studied.studied.

Almost all were epidemiological studies, Almost all were epidemiological studies, many with serious flaws and limitations.many with serious flaws and limitations.

Thimerosal was reduced in 2002-03 – Thimerosal was reduced in 2002-03 – these children are not 8 years old yet; these children are not 8 years old yet; flu shot raised exposures since.flu shot raised exposures since.

Early intervention can “artificially” Early intervention can “artificially” boost ASD rates among 3-year-olds by boost ASD rates among 3-year-olds by 75% (CDC study).75% (CDC study).

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METALSMETALSOrganic MercuryOrganic Mercury

Inorganic MercuryInorganic Mercury

AluminumAluminum

Arsenic Arsenic

Antimony – flame retardantsAntimony – flame retardants

Lead/Tin/Cadmium etc.Lead/Tin/Cadmium etc.

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GLUTATHIONE:GLUTATHIONE:

Sulfur-based protein that binds with Sulfur-based protein that binds with heavy heavy metalsmetals, viruses and toxins to eliminate them , viruses and toxins to eliminate them from system. from system.

Very powerful fighter against Very powerful fighter against oxidative stressoxidative stress..

Critical for protecting Critical for protecting mitochondrialmitochondrial membranes from permeation/damage caused membranes from permeation/damage caused by toxins.by toxins.

TylenolTylenol blocks glutathione production in the blocks glutathione production in the liver.liver.

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ASD kids have low or depleted levels of “thiols,” ASD kids have low or depleted levels of “thiols,” including glutathione.including glutathione.

Thiols are Thiols are mercaptansmercaptans, Latin for “capturing mercury.”, Latin for “capturing mercury.”

Targeted nutritional intervention with Folinic acid, Targeted nutritional intervention with Folinic acid, and Betaine resulted in significant improvement in and Betaine resulted in significant improvement in ASD children.ASD children.

Addition of methyl B-12 to “cocktail” brought all ASD Addition of methyl B-12 to “cocktail” brought all ASD children within normal “thiol” levels, such as children within normal “thiol” levels, such as glutathione.glutathione.

Thimerosal damage to nerves was associated with Thimerosal damage to nerves was associated with glutathione depletion, protection was restored with glutathione depletion, protection was restored with glutathione precursors. glutathione precursors.

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““Changes in Changes in astrocytesastrocytes and and microgliamicroglia in primate brains after long-term in primate brains after long-term methylmercury exposure.”methylmercury exposure.”

Burbacher: Inorganic Hg, presumably from Burbacher: Inorganic Hg, presumably from methyl Hg, continued to increase throughout all methyl Hg, continued to increase throughout all exposure durations.exposure durations.

Both Both astrocyte astrocyte andand microglial microglial cells had cells had “substantially elevated” inorganic mercury “substantially elevated” inorganic mercury deposits. deposits.

““Inorganic Hg in the brain may be a toxic form Inorganic Hg in the brain may be a toxic form responsible for responsible for activation activation ofof astrocyte astrocyte andand microglia.” microglia.”

Activation of Activation of astrocyte astrocyte andand microglial microglial cells was cells was not noted for six months or more, in some cases.not noted for six months or more, in some cases.

Neurotoxicology. 1996;17:127-138.

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HARVARD:HARVARD:“Large Brains in Autism: The “Large Brains in Autism: The

Challenge of Pervasive Challenge of Pervasive Abnormality” Abnormality”

The NeuroscientistThe Neuroscientist, Volume 11, Number 5, 2000, Volume 11, Number 5, 2000

Neuro-inflammation, oxidative Neuro-inflammation, oxidative stress & stress & microgliamicroglia damage found in damage found in autistic brain tissue. autistic brain tissue.

“Chronic disease or external “Chronic disease or external environmental sources” (ie, heavy environmental sources” (ie, heavy metals) may be the cause. metals) may be the cause.

““Oxidative stress, brain Oxidative stress, brain inflammation, and inflammation, and microgliosismicrogliosis has has been much documented in been much documented in association with heavy metal association with heavy metal exposures.”exposures.”

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CDC -VSD:CDC -VSD: Thimerosal and Thimerosal and Neurodevelopmental Neurodevelopmental

DisordersDisorders

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Study looked at Texas county levels of Study looked at Texas county levels of emissions, compared to ASD rates and special emissions, compared to ASD rates and special ed in 1,200 school districts. ed in 1,200 school districts.

Autism increased as mercury emissions rose. Autism increased as mercury emissions rose. For every thousand pounds of Hg, there was a For every thousand pounds of Hg, there was a 61 percent increase in autism rates.61 percent increase in autism rates.

One county with low mercury emissions but One county with low mercury emissions but significant autism rates was found to harbor significant autism rates was found to harbor one of the nation’s largest mercury mines. one of the nation’s largest mercury mines.

““A potentially important connection between A potentially important connection between environmental exposure to mercury and the environmental exposure to mercury and the development of autism.”development of autism.”

UNIV of TEXAS - 2005: “HIGHER RISK OF AUTISM NEAR COAL-FIRED PLANTS” - Health & Place - 12 (2006) 203-20912 (2006) 203-209

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Myelin:Myelin:

“A white fatty substance “A white fatty substance that forms a sheath that forms a sheath

around nerve fibers to around nerve fibers to provide electrical provide electrical

insulation” insulation”

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The Bailey Banks CaseThe Bailey Banks Case Court ruled MMR vaccine produced Court ruled MMR vaccine produced acute acute

disseminated encephalodisseminated encephalomyelitismyelitis (ADEM) – (ADEM) – Inflammation of brain and spinal cord and Inflammation of brain and spinal cord and damage to the damage to the myelin sheath.myelin sheath.

ADEM can be caused by natural infections, ADEM can be caused by natural infections, especially measles virus. But is also a post-especially measles virus. But is also a post-vaccine injury, especially rabies, pertussis, vaccine injury, especially rabies, pertussis, influenza, and influenza, and MMRMMR..

1994 IOM: Biologically plausible for a vaccine to 1994 IOM: Biologically plausible for a vaccine to “induce...an autoimmune response...by “induce...an autoimmune response...by nonspecific activation of the T cells directed nonspecific activation of the T cells directed against against myelinmyelin proteins.” proteins.”

Symptoms: headache, delirium, lethargy, seizures, Symptoms: headache, delirium, lethargy, seizures, stiff neck, fever, ataxia (incoordination), nausea, stiff neck, fever, ataxia (incoordination), nausea, vomiting, weight loss, irritability, changes in vomiting, weight loss, irritability, changes in mental status.mental status.

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Banks Cont’dBanks Cont’d Bailey had MRI 16 days after MMR vaccine, Bailey had MRI 16 days after MMR vaccine,

confirmed his diagnosis. Most given Tylenol confirmed his diagnosis. Most given Tylenol and sent home.and sent home.

Tylenol can affect glutathione, Tylenol can affect glutathione, mitochondrial function and oxidative stress.mitochondrial function and oxidative stress.

A A smallsmall study at UCSD showed kids given study at UCSD showed kids given Tylenol after MMR were Tylenol after MMR were several timesseveral times more more likely to develop ASD. likely to develop ASD.

"Tylenol and MMR was significantly "Tylenol and MMR was significantly associated with autistic disorder," the associated with autistic disorder," the authors wrote.authors wrote.

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BanksBanks

““Bailey’s ADEM was severe enough to Bailey’s ADEM was severe enough to cause lasting, residual damage, and cause lasting, residual damage, and retarded his developmental progress, retarded his developmental progress, which fits under the generalized which fits under the generalized heading of PDD-(NOS).” heading of PDD-(NOS).”

““Bailey would not have suffered this Bailey would not have suffered this delay but for the administration of delay but for the administration of MMR.MMR.

““A proximate sequence of cause and A proximate sequence of cause and effect leading effect leading inexorably from inexorably from vaccination to PDDvaccination to PDD.”.”

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HepB, Myelin and MSHepB, Myelin and MS Vaccine Court – 65 HepB-Vaccine Court – 65 HepB-DemyelinatingDemyelinating

Cases.Cases.

Sample case: Court ruled adult female Sample case: Court ruled adult female contracted a demyelinating disease and contracted a demyelinating disease and MS, and eventually died, after receiving the MS, and eventually died, after receiving the Hepatitis B vaccine series.Hepatitis B vaccine series.

Just the most recent case in a rash of Just the most recent case in a rash of rulings on HepB and “demyelinating rulings on HepB and “demyelinating diseases such as transverse myelitis (TM), diseases such as transverse myelitis (TM), Guillain-Barré syndrome (GBS), chronic Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating disease inflammatory demyelinating disease (CIDP), and multiple sclerosis (MS).”(CIDP), and multiple sclerosis (MS).”

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HepB and Myelin in HepB and Myelin in InfantsInfants

Oct. 2008 issue of Oct. 2008 issue of Neurology - Neurology - Hep B Hep B vaccine in infants associated with a 50% vaccine in infants associated with a 50% increased risk for CNS increased risk for CNS inflammatory inflammatory demyelinationdemyelination..

Especially true for GSK’s Engerix B Especially true for GSK’s Engerix B

vaccine - Risk was 74%. Among ASD vaccine - Risk was 74%. Among ASD children with MS it increased 177% children with MS it increased 177%

““The Engerix B vaccine appears to The Engerix B vaccine appears to increase this risk, particularly for increase this risk, particularly for confirmed multiple sclerosis, in the confirmed multiple sclerosis, in the longer term. longer term.

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Mitochondria:Mitochondria:“Powerhouse of the cell that “Powerhouse of the cell that

converts food and oxygen into converts food and oxygen into energy”energy”

Mitochondrial Dysfunction:Mitochondrial Dysfunction:Low cellular energy caused by Low cellular energy caused by

genes or environmental genes or environmental factors such as metals and factors such as metals and

drugs, including drugs, including antidepressants and Tylenolantidepressants and Tylenol

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Hannah Poling Concession Hannah Poling Concession November 9, 2007November 9, 2007

Hannah met all milestones in first 18 months. Hannah met all milestones in first 18 months. At 9 monthsAt 9 months: Mimicking sounds, crawling, and : Mimicking sounds, crawling, and sitting.sitting.

At 12-monthAt 12-month pediatric visit: Saying “Mom” & pediatric visit: Saying “Mom” & “Dad,” pulling self up, cruising. “Dad,” pulling self up, cruising.

July 19, 2000 July 19, 2000 visitvisit - Hannah “spoke well” was - Hannah “spoke well” was “alert and active,” with regular bowel “alert and active,” with regular bowel movements and good sleeping habits.movements and good sleeping habits.

July 19, 2000July 19, 2000 visit – Hannah received 9 visit – Hannah received 9 vaccines: vaccines: D-T-aP, M-M-R, Hib, Varivax, and PolioD-T-aP, M-M-R, Hib, Varivax, and Polio

Followed by fevers, rashes, and descent into Followed by fevers, rashes, and descent into ASD.ASD.

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Poling Concession #2Poling Concession #2February 21, 2008February 21, 2008

Amended report from Dr. Zimmerman:Amended report from Dr. Zimmerman:

““The cause for regressive encephalopathy at The cause for regressive encephalopathy at age 19 months was underlying mitochondrial age 19 months was underlying mitochondrial dysfunction, exacerbated by vaccine-induced dysfunction, exacerbated by vaccine-induced fever and immune stimulation that exceeded fever and immune stimulation that exceeded metabolic reserves.” Epilepsy was “part of metabolic reserves.” Epilepsy was “part of the same pathogenesis that led to autistic the same pathogenesis that led to autistic encephalopathy.”encephalopathy.”

SHORT VERSION: Hannah’s autism was SHORT VERSION: Hannah’s autism was caused by a vaccine-induced exacerbation of caused by a vaccine-induced exacerbation of her underlying mitochondrial dysfunction.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”

In the central nervous system, continued use of damaged mitochondria and impaired metabolic function may generate additional oxidative stress.

This oxidative stress causes further activation of the immune system, leading to even more oxidative stress.

Such a mechanism would self-sustain and possibly progressively worsen.

Mitochondrial dysfunction found in autism would activate both astroglia and microglia. These activated cells can then initiate a broad-spectrum pro-inflammatory gene response.

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Seven Studies to WatchSeven Studies to Watch 1) Unanimous endorsement by the National Vaccine Advisory Committee 1) Unanimous endorsement by the National Vaccine Advisory Committee

to look at the feasibility of a large vaccinated-unvaccinated study, with to look at the feasibility of a large vaccinated-unvaccinated study, with autism as an outcome.autism as an outcome.

2) NVAC endorsement of vaccine-autism investigations into children with 2) NVAC endorsement of vaccine-autism investigations into children with mitochondrial dysfunction.mitochondrial dysfunction.

3) NVAC endorsement of vaccine-autism investigations into children with 3) NVAC endorsement of vaccine-autism investigations into children with regressive form of ASD (15-55%).regressive form of ASD (15-55%).

4) NVAC endorsement of investigations into vaccine injuries such as 4) NVAC endorsement of investigations into vaccine injuries such as encephalitis, seizure disorders and demyelinating diseases at risk factors encephalitis, seizure disorders and demyelinating diseases at risk factors for ASD.for ASD.

5) NIH Early Autism Risk Longitudinal Investigations EARLI study which 5) NIH Early Autism Risk Longitudinal Investigations EARLI study which will follow 1,200 pregnant mothers with one ASD child, looking at all will follow 1,200 pregnant mothers with one ASD child, looking at all environmental triggers, including metals, thimerosal and vaccines.environmental triggers, including metals, thimerosal and vaccines.

6) HHS/EPA National Children’s Study, which will follow 100,000 children 6) HHS/EPA National Children’s Study, which will follow 100,000 children and look at all environmental factors and outcomes, including metals, and look at all environmental factors and outcomes, including metals, vaccines and ASD.vaccines and ASD.

7) CDCs Centers for Autism and Developmental Disabilities Research and 7) CDCs Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) Network, to study, "mercury exposures, including Epidemiology (CADDRE) Network, to study, "mercury exposures, including any vaccine use by the mother during pregnancy and the child's vaccine any vaccine use by the mother during pregnancy and the child's vaccine exposures.”exposures.”

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ASD and Mitochondria – ASD and Mitochondria – PloS Online – 12/08PloS Online – 12/08

Scientists at Cleveland Clinic, Harvard Scientists at Cleveland Clinic, Harvard and Johns Hopkins: "There might be no and Johns Hopkins: "There might be no difference between the inflammatory or difference between the inflammatory or catabolic stress of vaccinations and that catabolic stress of vaccinations and that of common childhood diseases.”of common childhood diseases.”

"Large, population-based studies will be "Large, population-based studies will be needed to identify a possible relationship needed to identify a possible relationship of vaccination with autistic regression in of vaccination with autistic regression in persons with mitochondrial cytopathies." persons with mitochondrial cytopathies."

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Dr. Duane Alexander - Dr. Duane Alexander - NICHDNICHD

““Important to ask if some children Important to ask if some children are more susceptible to some vaccine are more susceptible to some vaccine characteristic or component, and may characteristic or component, and may develop an ASD in response.”develop an ASD in response.”

There may be "subpopulations unable There may be "subpopulations unable to remove mercury from the body as to remove mercury from the body as fast as others, or some adverse or fast as others, or some adverse or cross-reacting response to a vaccine cross-reacting response to a vaccine component, or a mitochondrial component, or a mitochondrial disorder increasing the adverse disorder increasing the adverse response to vaccine-associated fever.”response to vaccine-associated fever.”

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Dr. Anthony Fauci - Dr. Anthony Fauci - NIAIDNIAID

"If we can show that individuals "If we can show that individuals of a certain genetic profile have a of a certain genetic profile have a greater propensity for developing greater propensity for developing adverse events, we may want to adverse events, we may want to screen screen everyoneeveryone prior to prior to vaccination."vaccination."

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The “1322 Project”The “1322 Project” Announced at Autism One - Expert legal review of Announced at Autism One - Expert legal review of

previous Vaccine Court decisions to determine ASD previous Vaccine Court decisions to determine ASD prevalence.prevalence.

Preliminary results show ASD rate many times Preliminary results show ASD rate many times higher than 1-in-150. Final results to be announced higher than 1-in-150. Final results to be announced soon.soon.

CBS Evening News: At least 1322 cases paid out for CBS Evening News: At least 1322 cases paid out for vaccine-induced brain damage, encephalopathy vaccine-induced brain damage, encephalopathy and/or seizure disorders.and/or seizure disorders.

““There may be cases involving autistic-like There may be cases involving autistic-like disorders which manifested following a Vaccine disorders which manifested following a Vaccine Injury Table injury. Any residual effects thereof Injury Table injury. Any residual effects thereof would be presumedwould be presumed to be vaccine-caused. Autism to be vaccine-caused. Autism cases involving Table Injuries have been cases involving Table Injuries have been compensated.” compensated.” – – Gary J. Golkiewicz, Vaccine Court Chief Special Gary J. Golkiewicz, Vaccine Court Chief Special MasterMaster