AUTISM CYMRU

1
AUTISM CYMRU
By special arrangement with Joe Calzaghe
Paul Shattock University of Sunderland
The Use of Medications in the Treatment of People
with Autism Spectrum Disorders
Cardiff City Hall, April 22nd 2008
2
In order to discuss the role of interventions,
including medications and nutritional
manipulations it is necessary to have a
theoretical model.
Such a model must be based on current scientific
and clinical observations.
Facts are sacred. Interpretations will evolve
with increased understanding.
Our current hypotheses may be wrong but represent
a best fit based on current knowledge,
understanding (and fashion).
3
The mechanisms described are probably part, but
not all, of the story.
For example opioid peptides will affect
transmission in all the systems of the central
nervous system. They will
affect the immune system ..and the
gastrointestinal system.
The guts, the nervous system and the immune
system are derived from the same embryological
tissues.
Unlike the residents of the this island, they use
the same chemical language.
4
This presentation is divided into two parts
(separated by light refreshment).
Part 1. The development of an overall theoretical
model.
Part 2. a) How current interventions fit into the
overall plan. b) Some possibilities in
various stages of development and testing.
5
Four Pillars For Effective Support
1. Enhancement of Respect and Dignity
2. Biology, underlying forces
6
Must consider all these elements
For example-
The child who lies over the chair all day.
7
Does anyone know a gastro-enterologist, anywhere
in the UK, who will investigate GI problems in
people with Autism Spectrum Disorders?
8
Must consider all these elements
For example-
The child who lies over the chair all day.
The child who eats the bark from trees.
The child who loves salty things, the child who
detests or fears the colour orange.
9
Four Pillars For Effective Support
1. Enhancement of Respect and Dignity
2. Biology, underlying forces
3. Care- Protection and Encouragement
4. Education
The pillars are of no use in isolation. Remove
any of the pillars and the edifice collapses.
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Baird G., Simonoff E., Pickles A., Chandler S.,
Loucas T., Meldrum D., Charman A. Prevalence of
disorders of the autism spectrum in a population
cohort of children in South Thames the Special
Needs and Autism Project (SNAP) Lancet 368
210-215 (2006)
9-10 year old children in N.E. London Total
Prevalence of PDD 116.1 in 10,000
equivalent to 186 children
Estimates of 410,000 now 11610,000.
?
Previously missed 97
Suggest ratio of boysgirls now 81
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ONE in 86 CHILDREN is equivalent to ONE in 50
BOYS
Aged 9-10 will include all spectrum (NB This is
NOT ADHD, Dyslexia and other NeuroDiverse
conditions)
12
Shattock Paul, Whiteley Paul, Todd Lynda.
Is there an Increasing Incidence of Autism?
evidence and possible explanations.
Consensus in Child Neurology (Supplement of
Journal of Child Neurology) November 2002 29-34
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ONE SIMPLIFIED ROUTE MAP TO AUTISM
Numerous Genes act separately or in combination
Sulphation
Methylation
Amino-Acids
e.g. Lactase
Variety of Symptoms of Autism
14
Are there any diseases which are either totally
genetic or totally environmental in origin?
Same Environment Different Genes
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Are children with ASDs the same all over the
world?
If the environmental factors are different, will
people with autism be the same as they used to be?
Are more children diagnosed now? Have borders
been extended?
Has earlier and more effective intervention had
an effect?
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Are children with ASDs the same all over the
world?
Bahrain and later onset of Symptoms
10 of 22 children (45) showed no signs until 20
months mainly 24 months (probably an
underestimate)
Koran requires breast feeding to continue until
age of 2.
Presentational differences sociability?
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Male Female Ratios For ASDs
Usually accepted Figure 3-4 to 1
Recent Figures from UK 7-8 to 1
Data from Iran (In Press JADD) 1 to 1
Lack of male births in Northern Canada
Left handedness tripled in UK in 20 yrs
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Intestinal Dysbioses
John Hunter (Cambridge) Sophie
Rosseneu (Royal Free,London) Glen Gibson (Reading)
Use of antibiotics during pregnancy and early
infancy
Caesarian births
Problems with establishment of appropriate
bacteria.
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What environmental factors may be involved with
different individuals?
Diet gluten, casein, corn, soya, GM products,
MSG, Aspartame, eggs, beef, avocado, allergenic
foods.
Natal Issues ultrasonics, cord cutting, Rhogam,
antibiotics, drugs, hypoxia/anoxia, infections
vitamin K, folate, alcohol, deficiencies of
essential vitamins, minerals. fatty acids.
Exposures (especially during term) pesticides,
PCBs, dioxins, bisphenols, mobile phones, heavy
metals, immune and endocrine modulators,
infections, vaccines.
Physical Factors Head trauma, gut or CNS ops,
Mental Stress exacerbation of all symptoms
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ONE SIMPLIFIED ROUTE MAP TO AUTISM
Numerous Genes act separately or in combination
Sulphation
Methylation
Amino-Acids
e.g. Lactase
Many Environmental Triggers varying with Location
History
Infection History
Vaccinations
Pesticides
Dietary Status
Metals (Heavy and essential)
Gut Dysbioses
????????????
Variety of Symptoms of Autism
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ONE SIMPLIFIED ROUTE MAP TO AUTISM
Numerous Genes act separately or in combination
Sulphation
Methylation
Amino-Acids
e.g. Lactase
Many Environmental Triggers varying with Location
History
Infection History
Vaccinations
Pesticides
Dietary Status
Metals (Heavy and essential)
Gut Dysbioses
????????????
Opioid Peptides
Carbohydrates
Other Metabolites
Common Final Pathways
Neurotransmitters
Physical Structures
Variety of Symptoms of Autism
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Genetic Fragility
Environmental Stressors - Cumulative.
23
Some dietary products that are more common in a
maritime diet.
Elements Iodine, Selenium, Zinc
Fish Oils containing readily available omega
three fatty acids
Vitamins from fish Vitamin A, D and some B
group (B12)
Human EVOLVED near the sea. Our nutritional
requirements assume that we are still there.
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What is Beta-Endorphin?
A peptide with morphine-like activity which
occurs naturally in certain brain areas
(endogenous morphine endorphin)
Some reported effects of beta-endorphin
1. Altered Pain Sensitivity - (Antinociceptive
Effect) Particularly at times of stress.
2. Altered EEG patterns - involvement with
epilepsy
3. Modification of sleep patterns
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Some reported effects of beta-endorphin (cont)
4. Effects on Memory and Learning - Reward
leading to reinforcement and motivation
5. Decrease in Sociability
6. Involvement in Stereotypy/hyperactivity
7. Modification of Intake of Food and Drink
8. Constipation - Abnormal Poo
9. Regulation of Body Temperature
There are many other effects. This list is by no
means exhaustive
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Hypotheses
1. Peptides interfere with neurotransmission in
all the major systems of the C.N.S.
2. These peptides are derived from the
incomplete digestion of food, principally
gluten and casein, in the Gastro-Intestinal
Tract.
3. These peptides cross into the bloodstream
and can enter the C.N.S. to exert their
effects.
27
What are these biologically active compounds?
PEPTIDES
PROTEINS are made up of very long chains of
AMINO-ACIDS. During digestion, proteins are
broken down into short chains called
PEPTIDES. Typically, peptides contain 2-8
amino-acids, but may be much larger (e.g.
beta-endorphin) Leu-ENKEPHALIN (A
naturally occurring neuropeptide)
Tyr-Gly-Gly-Phe-Leu Beta-CASOMORPHIN
Human Tyr-Pro-Phe-Val-Glu-Pro-Ile
Bovine Tyr-Pro-Phe-Pro-Gly-Pro-Ile
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These Peptides will affect transmission in the
C.N.S. and may therefore affect- Perception
(Vision, Hearing, Taste, etc) Cognition Behaviou
rs (e.g. Stereotypies) Mood Emotions C.N.S.
development (pruning of CNS) (Immune
System) (Gastro Intestinal Tract)
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THE TIMES Monday 21st April, 2008
Prof Jeremy Nicholson IC in
Nature Metabolic profiling can tell us how
specific aspects of a persons diet and how much
they drink are contributing to risks for certain
diseases and these are things that we cant
investigate by looking at a persons DNA.
They call such studies Metabolomics.
It seems we have been performing metabolomic
studies for almost 25 years.
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Control urine sample (no IAG present)
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Standard urine sample for person with ASD
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Beta casomorphin 1-7
Problems with casein
33
Urine profile Male (born 1986), ASD Behavioural
regression following MMR vaccine
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FIRST DEGREE RELATIVES
Mother 16/35
46 Father 13/34
42 Siblings 13/23
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Number with 20min peak
Percentage with 20min peak
35
trans indolyl-3-acryloylglycine IAG
36
Anderson RJ, Bendell DJ, Garnett I, Groundwater
PW, Lough WJ, Mills MI, Savery D, Shattock PEG.
Identification of Indoly-3-Acryloyl Glycine in
the urine of people with autism. Journal of
Pharmacy and Pharmacology 54 (2) 295-298 (2002)
37
Alcorn A., Berney T., Bretherton K., Mills M.,
Savery D., Shattock P.
Urinary Compounds in Autism
Journal of Intellectual Disability Research 48
(Part 3) 274-278 (March 2004)
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CAVEAT
Wright B et al. (Feb 25th 2005) Developmental
Medicine and Child Neurology 47 (3) 190-192.
Is the presence of urinary
indolyl-3-acryloyl glycine associated with autism
spectrum disorders?
No! (but)
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Sulphation Problems in ASDs?
Circumstantial Evidence Families with Migraines?
Baby jaundice? Rheumatoid Arthritis? Other
sulphate related issues.
P. SULPHATE
PARACETAMOL
P. GLUCURONIDE
ONE HOUR after PARACETAMOL determine ratio of
Paracetamol sulphate -------------------------
----- Paracetamol glucuronide
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WARING, R.H., NGONG, J., KLOVRZA, L. University
of Birmingham, School of Biochemistry, UK
MEAN RATIO OF SULPHATE / GLUCURONIDE AUTISM
0.87 /- 0.67 (n 46) CONTROL 2.09
/- 0.65 (n 46) p lt 0.005 PLASMA
SULPHATE LEVELS AUTISM 1.51 /- 2.75 (n
14) CONTROL 8.30 /- 5.40 (n 14) p lt
0.001
41
Alberti A., Pirone P., Elia M., Waring R., Romano
C. A sulphation deficit in autistic children a
pilot study. Biological Psychiatry 8 420-424
(1999)
42
Sulphur Metabolism in Autism Waring Klovrza
(2000) Journal of Nutritional and Environmental
Medicine 10, pp25-32
Results Autism (n232) Controls
(n68) Age 7.6 2.4 8.5 3.7 Sulphite 106.9
162.9 2.1 6.3 Sulphate 6819.0
6712.3 3030.8 1461.0
Protein 103.2 89.9 64.5 27.5
Thiosulphate 130.8 148.1 18.6
25.0 Thiocyanate 6.4 16.9
44.0 101.0
Anion excretion in nmol/ml. Mean SD plt0.001
(Wilcoxon rank sum test)
43
Effects of lack of sulphating ability-
1. Neurotransmitters not removed from system
2. Toxic substances not removed from system - OP
pesticides? Metals? Bile pigments Phenolics.
3. Mucus lining of GI tract becomes patchy
-increases permeability of intestines
4. GAGs of GI wall less sulphated - increases
permeability of intestinal wall
5. Loss of activity of certain hormones (CCK and
Gastrin?) and resulting malabsorptions
6. Easing of access for Yeasts.
44
A
B
GUT
GUT
BLOOD
BLOOD
BRAIN
BRAIN
C
D
GUT
GUT
BLOOD
BLOOD
BRAIN
BRAIN
GUT PERMEABILITY ?
GUT PERMEABILITY ?
BLOOD-BRAIN- BARRIER PERMEABILITY ?
45
One, highly controversial, example where a
relationship between a genetically determined
fragility and environmental factors is suggested
but not proven or disproven.
Possible relationship between MMR vaccination and
some regressive ASDs
Other environmental suboptimalities such as
giving the vaccine to a child who is already sick
(viral infections including chicken pox
(varicella). Role of Mercury?
46
If you are in need of a good laugh
Google my name on the internet.
Each General Practice receives almost 8,000 each
year for reaching targets for MMR
vaccination. Who has the vested
interest? Normally one is only paid for doing
something one would not do anyway. I DO NOT
believe that GPs only vaccinate for the money but
are there any other products for which similar
systems apply?
1. It seems I had my snout in the trough during
the MMR case.
I hereby declare my vested interest in that over
eight year period I received in total (according
to newspaper reports) 8,000.
Much of this was expenses (travel etc). Most of
my work was not charged for.
47
IF (as current research indicates) ASDs are
occurring at a rate of 1 in 86 births
and the UK parents are telling the truth 6.7
of ASDs are triggered by MMR
ONE BRITISH CHILD IN 1,280 WILL BE RENDERED
AUTISTIC BY MMR VACCINE
IF the US parents are telling the truth and 50
of ASDs are triggered by MMR
ONE American child in 200 will be rendered
autistic by MMR vaccination.
ONE AMERICAN BOY IN 140 WILL BE AUTISTIC BY MMR
VACCINATION
48
Some clinical signs that may correlate with
vaccine involvement in causation of autism.
1. Unusual sociability and friendliness.
2. Development of unusual thirst.
3. Abnormal Gait - flat-footed, padding
- wide gait toe walking.
4. Development of bowel problems
-
constipation and diarrhoea.
It is recognised that all of the above occur in
many children with autism but the cluster of
symptoms may be characteristic of this sub-group.
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MUNCHAUSEN SYNDROME BY
PROXY
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If you are in need of a good laugh
Google my name on the internet.
1. It seems I had my snout in the trough during
the MMR case.
2. It is implied that I have faked my
qualifications (Dip.Ag.Vet.Pharm.)
I am the only academic in the UK with this
Qualification but rarely quote it at Autism
events because it is not relevant. However.it
is now extremely relevant.
52
Transition to OP pesticides
ABBA win Eurovision Song Contest
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Other circumstantial evidence-
1. Higher rate of ASDs in rural than urban areas.
Budd R., UK Autism Demographics Perspectives
on Progress (2000) 207-214
54
Maternal Residence Near Agricultural Pesticide
Applications and Autism Spectrum Disorders Among
Children in the California Central Valley
Roberts E.M., English P.B., Grether
J.K., Windham G.C., Somberg L., Wolff C. National
Institutes of Health, U.S. Dept of Health and
Human Services
July 2007 Environmental
Health Perspectives http//dx.doi.org/
Reports increased incidence of ASDs the closer
one lives to fields sprayed with pesticides
(certain organochloride) and when the spraying
occurs at time of foetal CNS development.
Suspicions about Organophosphates but sample
number too small?
55
Other circumstantial evidence-
1. Higher rate of ASDs in rural than urban areas.
Budd R., Roberts et al.
2. Behavioural effects of Malathion lotions for
treatment of headlice.
3. Seasonal Effects at dipping and spraying
time in rural communities.
4. Effects of accidental spraying.
5.Considerable anecdotal evidence for
effectiveness of organic diets.
6. Biochemical Plausibility. Many abnormalities
in ASDs explicable by OP involvement.
56
We have studied possible links between
organophosphate pesticides and ASDs since 1995
last publication was in 2002
Our data were intriguing but did not make sense.
If it doesnt make sense it is probably important.
In 2007 there is more understanding and our
results have been reinterpreted and makes sense.
Are they relevant?
57
Metabolism of phenylalanine in states of
hyperphenylalaninaemia
COOH
COOH
X
Tyrosine
CH
CH2 CH
CH2
CH2COOH
Phenylketonuria
NH2
NH COCH3
Phenylalanine
N-acetylphenylalanine other metaboiites
dopa decarboxylase
OH
p-hydroxyphenol
pyruvate oxidase
dopamine beta-hydroxylase
transaminase
o-hydroxyphenol- acetate
OH
CH2 CO COOH
CH2 CH2 NH2
CH2 CH2 NH2
aromatic alpha-ketoacid reductase
Phenylpyruvate
Phenylethylamine
Phenylethanolamine
OH
MAO
MAO
CH2 CH COOH
Phenylacetyl - CoA
(Aldehyde)
(Aldehyde)
Phenyllactate
OH
CH2 CO NH
CH2 COOH
CH CH2 CH2 CO NH2
CH COOH
Phenylacetate
COOH
Mandelate
Phenylacetylglutamine
58
Some elements of the Metabolism of Tryptophan
3-Indole Acetic Acid (3-IAA)
Indole and Indican
3-Indole Propionic Acid
Kynurenine and derivatives
3-Indole Pyruvic Acid
TRYPTOPHAN
Organo-phosphate inhibition
(tryptophan hydroxylase)
3-Indole Acrylic Acid (IAcrA)
5-Hydroxy Tryptophan
(5-Hydroxytryptophan decarboxylase)
3-Indolyl Acryloyl Glycine (IAG)
Melatonin
5-Hydroxy Tryptamine (5-HT Serotonin)
Bufotenin
5-Hydroxy Indole Acetic Acid (5-HIAA)
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How do organophosphates kill?
As a nerve impulse passes from one nerve to
another OR from a nerve to a muscle a chemical
transmitter is involved.
Very often, this transmitter is Acetylcholine
Acetycholine is broken down, immediately, by
choline-esterase enzymes.
OPs have anticholine-esterase activity.
Acetylcholine persists so nerve impulse or muscle
contraction continues paralysis.
61
How do OPs become active?
The parent molecule (as spread on crops) has
little anticholinesterase activity. Bulk of
Activity resides in metabolites.
Malaoxon Diazoxon Paraoxon
Malathion Diazinon Parathion
Fat soluble OPs are made water soluble and can
become 1000 times more active.
This is the first stage in removal of toxins.
62
Metabolism of OP Insecticides
Parent OP (Malathion, Diazinon,)
Cytochrome P450 system
Active water soluble oxon form
(Maloxon, Diazoxon)
Paraoxonase enzymes
Excreted Metabolites
63
Metabolism of OP Insecticides
Parent OPs Malathion and Diazinon Thioates
Cytochrome P450 system especially 1A2 and 3A4
1A2 and 3A4 are Suicide Enzymes when reacting
with Thioates
Other substrates for 12A and 3A4 will persist
Testosterone and Estradiol
Elevated Testosterone in Amniotic Fluid of Babies
who develop ASD (Baron-Cohen)
64
DAmelio M., Ricci I., Sacco R., DAguma L.,
Muscarella LA., Guarniri V., Militerni R.,
Bravaccio C., Elia M., Schneider C., Melmed R.,
Trillo S., Pascucci T., Puglisi-Allegra S/.
Reichelt K-L., Macciardi JJA., Persico AM.
Paraoxanase (PON1) gene variants are associated
with autism in North America but not in Italy
possible regional specificity in gene
environment interactions Molecular Psychiatry
10 1006-1016 (2005)
65
SNP Genotyping for the PON1 Polymorphism G(192)A
Mutant Allele
Normal Allele
Mutant Allele
Normal Allele
Normal Allele
Mutant Allele
66
Some astonishing slides taken from the
presentation of Prof Clement Furlong, University
of Washington, Seattle. http//www.gs.washington.e
du/faculty/furlong.htm
A must read for anyone interested in this field
67
OPs Blood Brain Barrier Permeability
1. Hypotheses involving Indole Acrylic Acid.
2. Studies demonstrating increased BBB
permeability with OPs. (Sinha C., 2003, Damani
K., 2004, Jones K, Abou-Donia M, 2004)
3. Pyridostygmine Bromide (PB) and GWS.
4. Opportunist xenobiotics and organisms a)
Prions and Mad Cow Disease ?? b)
Paraquat and Parkinsons Disease? c) Peptides
from food
68
OPs Blood Brain Barrier Permeability
Parran DK., Magnin G., Li W., Jortner BS., Ehrich
M. Chlorpyrifos alters functional integrity and
structure of an in vitro BBB model
NeuroToxicology 26 77-88 (2005)
Song X., Pope C., Murphy R., Lal B., Bressler B.
Interactive effects of paraoxon and
pyridostigmine on blood-brain barrier integrity
and cholinergic toxicity Toxicol. Sci. 78
241-247 (2004)
69
Paraquat
1-methyl-4-phenylpyridinium (MPP)
Paraquat would not normally be expected to cross
the blood brain barrier. Would this change if OPs
had increased permeability?
70
Prior studies have shown that people with
Parkinson's disease are over twice as likely to
report being expose to pesticides as people
without the disease, but few studies have looked
at this association in people from the same
family or have assessed associations between
specific classes of pesticides and Parkinson's
disease.
Nature Neuroscience 2008 via Reuters and BBC
Website 18th April 2008
71
ARE THERE OTHER SIMILAR COMPOUNDS INVOLVED
a) Lubricant additives, especially in planes,
affect cabin crews.
b) Glyphosate (Roundup) herbicide greatly
increased levels in GM crops.
72
Overlapping of Function
Systems are designed for particular function but
have other abilities.
If one system is suboptimal it is not fatal as
others take over the function.
Pressure on any part of system through too much
stressor or too little activity puts stress on
the whole redox system.
Benefits may not be directly related to known
effects.
73
Prof Jill James, University of Arkansas Experiment
al Biology Conference, San Diego March 2005.
Levels of the antioxidant Glutathione are
reduced in the blood of children with ASDs.
When glutathione is less available, then it is
easier for things to get out of balance and the
free radicals can cause more damage. children
with autism would be less able to detoxify heavy
metals.
74
Supportive Society
Spectrum of Treatment Modalities
Political Decision
Psychotherapy and Counselling
Exclusion Diets
Behavioural Approaches
Alteration of Environment
Traditional Teaching
Biomedical Approaches
Detox. Support
Sensory Cognitive Programmes
Symptomatic Medication
75
A new scientific truth does not triumph by
convincing its opponents and making them see the
light, but rather because its opponents
eventually die and a new generation grows up that
is familiar with it.
Max Planck - 1902
76
Press Release from the American Academy of
Pediatrics April1st 2008
Most recently, the AAP met with representatives
of Defeat Autism Now!...in an effort to
facilitate communication between pediatricians,
parents and researchers about the diagnosis and
treatment of children with autism. All advocates
for these children agee that further research is
needed regarding causes as well as safe and
effctive treatment.
We are full of hope that this is the beginning of
a thoughtfull partnership that will further
explore factors that might cause or contribute to
autism, as well as examine safe and effective
treatment approaches for families coping with
this condition.
77
Press Release from the American Academy of
Pediatrics April1st 2008
We are full of hope that this is the beginning
of a thoughtful partnership that will further
explore factors that might cause or contribute to
autism, as well as examine safe and effective
treatment approaches for families coping with
this condition. Stan Kurtz representative
of DAN!
Any Chance of it happening here? PS
78

THE SUNDERLAND PROTOCOL (Shattock Whiteley,
2000)
CEASEFIRE - Remove source of bullets 1.
CASEIN - 3 weeks 2. GLUTEN - 3 months
PRELIMINARY AGREEMENT 3. OTHER
FOODS - Food diary (Corn Soya Tomatoes
Avocado Beef et al) 4. TESTING - Vitamins,
Minerals, Amino Acids, Allergies (IgG,
IgE) Supplement as appropriate Zn, Ca,
Mg, Mb, A, C, B1, B3, B6 5. PARASITIC ORGANISMS
- Yeasts, Others
ACTIVE RECONSTRUCTION 6.
SULPHATION ISSUES - Epsom Salts
(Internal/External), MSM 7. ENZYME ACTIVITY -
Betaine Hydrochloride 8. FATTY ACIDS - Evening
Primrose Oil, Fish Oils,Cod Liver Oil (Vit. A),
Flax Seed 9. L-GLUTAMINE - Correct
Imbalance, Intestinal Nutrient 10. ENZYME
SUPPLEMENTATION - Bromelain, Seren-Aid,
EnZymAid. ____________________________________
___________________________________ 11.
5-HYDROXY TRYPTOPHAN (5-HTP) 14. MEGADOSE B6
Mg 12. PIGMENT-FREE 15. DIMETHYLGLYCINE
(DMG) 13. SALICYLATE-FREE 16. SPECIFIC
CARBOHYDRATE DIET
79
LIST OF DRUGS DEMONSTRATED AS BEING EFFECTIVE AND
SAFE IN THE TREATMENT OF AUTISM
May 2005. FDA fails to approve Risperidone
for use in Autism . Approved in September 2006.
80
The Sunderland Protocol
A logical system for the implementation of
biomedical interventions for people with autism
and related disorders.
The protocol is divided into three sections and
is based loosely upon the Northern Ireland Peace
Process 1. The Ceasefire - removal of guns and
bullets 2. The Preliminary Agreement

- and analysis of underlying
problems 3. Active Reconstruction - permanent
resolution.
81
Before you start.
1. Read and understand
2. Obtain professional support
3. Consider known conditions - Coeliac Disease
and amino-acids
4. Take a good, balanced,(GF/CF) vitamin and
mineral supplement.
82
Each therapy must be seen as a part of an overall
treatment programme. These biomedical
interventions are not alternatives to an
educational programme - they are complementary.
Each intervention must be seen as a time limited
experiment for that person. Only if the benefits
outweigh the problems - continue. If not - stop
it.
Be prepared to revisit failed interventions..
83
THE CEASEFIRE
1. Remove Casein Derivatives three weeks and
assess situation.

84
Milk from Cows is wonderful food for Baby Cows
.or for genetically modified humans those with
thick leather skins and horns.
85
Lucarelli et al (1995) - Effect of casein-free
diet (alone) (n36 age 8-13 yrs) control
group (n20) - Blind casein-challenge (placebo
vs. casein capsules) - IgE, IgA, IgM, IgG
antibodies to food antigens (pre-diet) -
Behaviour Summarised Evaluation (BSE)
86
Results Significantly elevated levels of -
IgA specific antibodies to casein,
ß-lactoglobulin - IgM IgG antibodies to
casein - IgM to lactalbumin Significantly
changes to BSE after 8 wks of diet (autistic
isolation, verbal communication, cognition)
Changes to BSE following casein-challenge
87
Food aint what it used to be.
Milk
1) Different Breeds (species)
2) Pasteurized homogenized
3) Days old (at best)
4) Cows fed on different food different fatty
acid component
5) US only (packed with hormones and antibiotics).
88
THE CEASEFIRE
1. Remove Casein Derivatives three weeks and
assess situation.
2. Remove Gluten and derivatives three months
(at least) - assess.
Separate elements to minimise side effects
Preliminary stage - remove obvious bullets.
89
Some transient negative effects following the
removal of gluten and/or casein from the diet of
people with autism These effects are variable in
extent but experience suggests that they may be
more apparent in younger and smaller children -
Anxiety - Clinginess - Crying and general
whinginess - Staring into space - Marked
decrease in movement / dizziness - Increased
frequency in urination / defaecation - Flu-type
symptoms
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91
E P I L E P S Y a Warning!
92

PRELIMINARY AGREEMENT
3. Keep a food diary - Idiosyncratic
effects (Corn soya eggs beef tomato avocado.)
4. Testing - vitamins and minerals -
allergies (IgE IgG others?) supplement or
remove as appropriate.
5. Parasitic organisms - consider
yeasts protozoa worms.
93
ACTIVE RECONSTRUCTION PROCESS
ACTIVE RECONSTRUCTION PROCESS
6. Sulphation Issues - Epsom salts MSM.
94
ACTIVE RECONSTRUCTION PROCESS
ACTIVE RECONSTRUCTION PROCESS
6. Sulphation Issues - Epsom salts MSM.
7. Enzyme activity - Betaine Hydrochloride.
8. Fatty Acids - a) evening primrose, b) fish
oils c) cod liver oil (Vit A) d) flax oil.
95
Fatty Acid Metabolism
Omega 3 Omega 6
Alpha-linolenic acid (ALA)
Linoleic Acid (LA)
EicosaPentanoic Acid (EPA)
Arachidonic Acid (AA)
DecaHexanoic Acid (DHA)
Inflammatory
EICOSANOIDS
Anti-Inflammatory
96
ACTIVE RECONSTRUCTION PROCESS
ACTIVE RECONSTRUCTION PROCESS
6. Sulphation Issues - Epsom salts MSM.
7. Enzyme activity - Betaine Hydrochloride.
8. Fatty Acids - a) evening primrose, b) fish
oils c) cod liver oil (Vit A) d) flax oil.
9. L-Glutamine correct imbalance nourish
intestines.
10. Enzyme supplementation - bromelain
SerenAid EnzymeAid Peptizyde
97
ACTIVE RECONSTRUCTION PROCESS
11. 5-Hydroxy Tryptophan (5HTP) - to bridge the
missing stage.
Importance of Vitamin B6 (Pyridoxine)
Role of Pyridoxyl-5-Phosphate - but
it cant cross the blood brain barrier
98
ACTIVE RECONSTRUCTION PROCESS
11. 5-Hydroxy Tryptophan (5HTP) - to bridge the
missing stage.
12. Pigment-free diet (sulphation issues).
13. Salicylate-free diet - prostaglandin
inhibition.
14. Megadose B6.
15. DiMethyl Glycine (DMG).
16. Specific Carbohydrate Diet.
99
Diagrammatic representation of a dopaminergic
synapse
Tyrosine
DOPA
Inhibition of DOPA formation
Inhibition of Tyrosine Hydroxylase
Key
Dopamine
Stimulation of D2 receptors
D1 receptor
Decreased release of Dopamine
D2 receptor
Dopamine
100
The same principles apply with all the main
neurotransmitter systems of the Central Nervous
System.
There are pre-synaptic receptors which are
stimulated by opioid peptides.
Thus, opioid peptides regulate transmission in
all the systems of the CNS.
They act as Neuro-regulators rather than direct
neurotransmitters.
101
Many drugs have a preference for one type of
receptor over the other.
For example Risperidone blocks D2 receptors
first. At higher concentrations it will block D1
receptors.
So at Low concentrations there will be
an INCREASE in transmission and at
higher concentrations a DECREASE in transmission
of Dopamine
102
Many drugs have a preference for one type of
receptor over the other.
For example Risperidone blocks 5HT1b receptors
first. At higher concentrations it blocks 5HT1a
receptors.
So at Low concentrations there will be
an INCREASE in transmission and at
higher concentrations a DECREASE in transmission
of Serotonin (5HT)
103
Bell Shaped Dose Response Curve (as seen with
Self Injurious Behaviour and Sulpiride (D2 gt D1
Antagonist)
- and with Naltrexone
Incidence
of SIB
Dose of Medication
104
We will get a bell shaped dose-response curve.
The Goldilocks Effect
The ideal dose will vary between individuals
and will depend upon the target symptom.
105
Nota Bene
There are at least 15 subtypes of Serotonin
receptors
There are at least 8 subtypes of Dopamine
Receptors
As well as affecting these receptors,there are
at least 6 opioid receptor subtypes
. receptors for GABA, Acetyl Choline, Adrenalin,
Noradrenalin, Amino-Acids such as glycine and
glutamine and many peptides
106
Cholinergic systems stimulate movement
Dopamine system stimulates or depresses
cholinergic system (on concentration)
GABA system stimulates or depresses dopamine
system (on concentration)
Endogenous peptides regulate all of above
to produce
a balanced, homeostatic system
Exogenous substances (peptides and drugs) will
disrupt or alter the balance.
107
Up regulation and down regulation of receptors -
depends upon degree of stimulation.
If greater stimulation - numbers of receptors or
sensitivity will decrease.
If decreased stimulation - numbers of receptors
or sensitivity will increase
108
We are still reliant upon empirical, as far as
possible, evidence based medicines.
109
The dose for children with ASDs will not be the
same as for other children because-
Transmission is different in ASD
People with ASDs do not metabolise drugs as
efficiently as Controls. Drugs persist for
longer.
110
The Choice of Medication

1. Drug,
2. Route of Administration,
3. Evidence of efficacy and safety in ASDs
   Professional support.

111
Dosage of Medication
1. May not be the same as for Neurotypicals or
other disorders.
2. Persistence due to deficiencies in sulphation,
methylation etc.
3. Titration start (very) low and increase
slowly. (5 x Half Life.)
4. Liquid Formulations (personalised) -use of
percutaneals or sublinguals?
112
Following Instructions
1. Take X times a day! spread out over the 24
hours. (Not at midnight)
2. Other instructions Avoid Milk Before or
After Meals. INSTRUCTIONS NOT JUST ADVICE!
3. In the UK estimated that 13 of medicines
taken as directed. No wonder they dont work!
113
Take with Water
The biggest cause of refusals to take medication
resolution is simple!
Oesophagus is not solid tube peristalsis is
required to move tablet or capsule.
Take with a minimum of 100ml of water. The
oesophagus is probably inflamed and very
sensitive in any case.
Would take take something causing pain?
114
Drug Interactions
Computers in Pharmacies should keep records of
all medications including herbals and Over the
Counter products.
Any adverse event must be recorded. Specific
(idiosyncratic) sensitivities occur.
Look for drugs with similar actions drugs with
opposite actions drugs which are detoxified
from the body using the same mechanisms drugs
which physically react in the stomach drugs
which react with alcohol or aspirin drugs with
complex interactions (antibiotics and birth
control pills) etc etc.
115
Side Effects
The drug without side-effects does not exist. No
side-effects means no activity.
A problem for Physicians and Pharmacists How
much to say?
Carers Parents, staff, professionals must be
aware of the possibilities and actively look for
them.
116
Some Examples of Side-effects
Antibiotics
Effects on intestinal bacteria and appearance of
resistant types and yeasts
Look for changes in intestinal function
(diarrhoea) and behaviour (positive or negative).
Use in short courses Consider
introduction of probiotics.
117
Some Examples of Side-effects
Diuretics to reduce blood pressure
Effects on water and potassium content.
Look for dryness of the mouth drinking more
fluids tiredness, nausea, irregular heartbeat,
mood or mental changes.
Reduce dose? Supplement Potassium salts,
118
Some Examples of Side-effects
Newer Neuroleptics (Risperidone, Olanzepine)
Classic stereotypies, constant movements,
dyskinesias (permanent).
Acquired Obesity is very common. Possibility of
Diabetes.
Use in short courses and reduce dose when
feasible (withdrawal dyskinesias?) Constant
vigilance!
119
Carers should look for and report
Increased restlessness or drowsiness
If any rapid and sudden changes occur THINK DRUG!
Skin rashes (of any sort)
High temperature
Weakness
Mood Changes/Confusion/Dizziness
Dryness of the mouth or thirst
Unusual colour or smell to the urine
Pains Persistent Cough
120
As populations age.
What was an appropriate dose becomes an
overdose..because-
The individuals size decreases.
Liver and kidneys, responsible for breakdown and
removal, lose efficiency.
Fat to muscle ratio decreases less drug stored
in fat. More is available and circulating in
blood stream.
121
Supportive Society
Spectrum of Treatment Modalities
Political Decision
Psychotherapy and Counselling
Exclusion Diets
REGULATORY DRUGS
Behavioural Approaches
Alteration of Environment
Traditional Teaching
Biomedical Approaches
Detox. Support
Sensory Cognitive Programmes
Symptomatic Medication
122
Some Potentially Useful Medications which with
regulatory effects
1. Piogliazone (Actos) (30-60mg/day)
Currently used for treatment of diabetes
Employed on account of potentially beneficial
anti-inflammatory and immune modulating effects.
Boris M., Kaiser C. et al. Effects on behavioral
symptoms in autistic children Journal of
Neuroinflammation 4 (3) 2007
Comments Encouraging results in children aged
3-17 who had not responded to biomedical
interventions. Preliminary study better outcome
measurements vital.
123
Some Potentially Useful Medications which with
regulatory effects
2. Anti-testosterone Drug - Leuprolide Acetate
(Lupron).
Employed on account of possibility of reducing
effects of Mercury and belief that Mercury is the
cause of autism. Interesting overlap with Male
Brain.
Geier D and Geier M. published report in Medical
Hypotheses only.
Potential for Side-Effects seriously limit uptake
and use by physicians. Suggest Serious Caution!
124
Some Potentially Useful Medications which with
regulatory effects
3. Spironolactone Once extensively used to
control high blood pressure.
Employed for anti-inflammatory and
immunomodulatory effects in brain and guts. Also
anti androgenic effects.
Bradstreet JJ., Smith S., Granpeesheh D.,
El-Dahr JM., Rossignon D. Spironoloctone might
be a desirable immunologic and hormonal
intervention in autism spectrum disorders
Medical Hypotheses (2006)pp xxxx
Comments Very plausible but largely anecdotal at
present Worth a formal trial under very
controlled conditions.
125
Some Potentially Useful Medications which with
regulatory effects
4. Very low dose Naltrexone (LDN)
An old friend revisited.
Formerly employed (at low doses) to inhibit
opioid activity. Reintroduced as immunomodulator
at VERY low doses.
Jacquelyn McCandless involved in current trials.
Publications rather speculative at present.
Comments Encouraging results with diabetes
(published) and other auto-immune disorders.
Important studies v AIDS in Africa. (Right
product formerly used for wrong reasons?)
126
Epsom Salts in Bathwater
Some drugs (Tylenol and some antipsychotics) rely
upon sulphation for metabolism and removal.
Existing levels of medications can be reduced and
effectiveness reduced. Side-effects could be
re-appearance of symptoms in original or modified
form.
127
There is no such thing as an effective
intervention that does not have a potential for
side-effects.
Whenever there is a change in health, behaviour,
or well-being... think drug
..even an apparently innocuous intervention can
result in unpredicted consequences sometimes
related to existing interventions.
128
Do we affect the rate of breakdown of drugs with
biomedical interventions?
By encouraging sulphation with Epsom Salts and
MSM?
By encouraging methylation with B12, Betaine,
Folic Acid?
By introduction of other foods or drugs using
same breakdown paths.
Available levels may change with sweating.
129
Genes can be switched on (or off) by
environmental elements-
Methylation
Phosphation
Propionic Acid (from intestinal bacteria?)
130
Gradual filling in the gaps in evidence. Practice
has preceded evidence.
Current (definitive) trials of gluten and casein
free diets (in Denmark).
Trials of Omega 3 containing Fish Oils. Takes
longer to produce significant results. Some non
responders (or negative responders).
131
The Rising Sun Coal Mine - Newcastle
Mining since 1650. Extremely polluted with heavy
metals and other chemicals.
A school was recently opened on this site
Rising Sun School for Autistic Children
132
Paul Shattock Autism Research Unit, School of
Health Sciences, University of Sunderland, SUNDERL
AND SR2 7EE Tel [phone] Fax [phone]
0420 autism.unit_at_sunderland.ac.uk http//osiris.su
nderland.ac.uk/autism/