Incomplete Brain Development In Autism: Causes & Treatment
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William J. Walsh, Ph.D. Pfeiffer Treatment Center Warrenville, IL
Pf ff
° ° ° ° ° °
à tpatient medical facility 23,000 patients from all 50 states and 75 foreign co ntries. Collaboration between medical doctors and scientists. Individ alized Biochemical Therapy Scientific Research 501c3 P blic Charity
Pf ff ° ° °
°
Chemistry Database St dies Metallothionein Research àidative Damage -- Essential fats -- Vasc lar tiss e -- Imm ne cells (le ocytes) -- Brain tiss e Assays of a tism/control brain tiss es.
Pf ff ° 10,600 ° ° °
Behavior & ADHD 6,000 A tism 3,700 Schizophrenia & Bipolar 3,600 Depression
Pf ff °
Abo t 90 to 150 assays of chemical factors in blood, rine, or hair for more than 6,000 patients
°
More than 1,000,000 separate chemical analyses
M P f
M ! ° °
" f# $ % & '(% R
° °
°
Major biochemical abnormalities observed thro gho t the a tism spectr m. The biochemical imbalances are more severe than those for ADHD, violent behavior, depression, and psychosis. Female a tistics have more disordered chemistry than male a tistics.
)| ° ° ° ° ° °
Elevated ser m copper Elevated toic metals Depressed zinc Undermethylation Pyrrole disorder Severe oidative stress & damage
° ° ° ° ° ° °
Depressed Methionine and SAMe Elevated SAH and Adenosine High Urinary Isoprostanes Depressed Cysteine and Gl tathione Low Seleni m Levels Depressed Cer loplasmin Elevated Levels of Free-Radicals
g f * +$ #
!
,
f $ $ $ f +$ ) ff
g$ # A tism Spectr m (N=503) Controls (N=25)
Mean C /Zn Ratio 1.63 1.15
t = 8.77 (two-tailed ³t´ test); - American Psychiatric Association Ann al Meeting New àrleans, 2001.
| ff . # P /# 0 ! /À
R
g
1. 2.
3.
Depletes metallothionein & gl tathione Associated with inflammation & ecessive oidative stress Can ca se abnormal ne rotransmitter levels.
.12 . - !
3 ! 3 !
3 3
"
* 2 | 4 ° ° ° °
Req ired for development of brain cells, Primary ³filter´ for Hg, Pb, and other metal toics at intestinal and blood/brain barriers, Req ired for homeostasis of C and Zn, S pports imm ne f nction. " " ! "
# #1# ° °
Short, dense, ndeveloped brain cells, Abnormalities observed primarily where MT levels are highest (amygdala, hippocamp s, P rinje cells, inferior olives, and pineal gland).
R á
f2
f ° ° °
MT-3 assists in the pr ning of brain cells, which maes space for growth of ³new´ cells, MT-1 and MT-2 participate in the nat ral growth (development) of brain cells, MT-3 is the primary agent for termination of growth of f lly-developed brain cells.
1 5 1 2'"# '# 6 25 7 GSH is first line of defense against Hg, Pb, etc, b t has limited capacity for toic metals. ° When > 10% of GSH is bo nd to toic metals, additional toics are transferred from GSH to MT. ° Se increases inetics of the GSH/MT antioidant system by more than 50%. ° For major epos res, most toic metals depart the body bo nd to MT.
°
2 P °
°
°
Form lation of 22 n trients that promote genetic epression or f nctioning of MT, incl ding Zinc, Gl tathione, and Seleni m, Aimed at completion of brain mat ration to enable gains in cognition, speech, and socialization, Has res lted in higher freq ency of a tism recovery at Pfeiffer Treatment Center. # P 8'!,!' 8 9 : '! 8;
+$ )# °
P blished in à # $ ~ <,< <0 A thors Pratico, Walsh, McGinnis, and Yao.
°
Findings: Elevated oidative damage to fats and vasc lar tiss es for a tistic s bjects, compared to controls.
) P. -
P
+$ )#! °
% & & $' ( ) *( (+ g ' 2" '* 'P
'# '.1 '
°
f$ )
°
g f )
| f+$
)# °
Untreated a tism may be ne rodegenerative with oidative damage ca sing slow, grad al loss of brain cells and IQ.
°
Antioidant therapy may be necessary thro gho t the life of a person diagnosed with an a tism spectr m disorder.
g 9 =8' ;f & ) °
Most yo ng ASD patients appear q ite bright
°
Many s ccessf lly treated children become mainstreamed and academic leaders,
°
Most ad lt a tistics ehibit mental severe retardation.
.5# J
, " - R R
! .$ O
! " : f ( )>09!; ,'! ?
.5 )f # ° ° ° ° °
SAMe levels 36% lower, SAMe/SAH ratios 50% lower, Homocysteine 180% higher, Cysteine 40% lower, GSH 25-60% lower.
.5#
g #
P
6 )2 'P '! 7 2 ' ~ 0'& !'2 '! ? W.McGinnis, T.A dhya, W.Walsh, J.Jacson, J.McLaren-Howard, A.Lewis, P.La da, D.Bib s, F.J rna, R.Lietha, A.Hoffer. ° °
! , f# $
P. ) 5 f $
@ A
f P @
9
f ;
<
< <
<
< P
< A
<
<<
fg . ( ° ° °
°
Do ble blind, controlled st dy, 176 brain tiss es & 22 peripheral samples from U. of Maryland¶s A tism Brain Ban, Elemental analysis for 16 elements, incl ding Hg, Pb, C , Zn, and Se sing high-brilliance photons at ANL¶s Advanced Photon So rce), First elemental assays ever attempted for a tism & control brain tiss es.
) # Cerebell m ° S perior Corte ° Deep Corte ° White Matter °
# (/(
# f ) °
Abnormal levels of Ca, S, Fe, Zn in a tism brains,
°
The abnormalities are striingly different for male and female a tistics, s ggesting that male and female a tism may have different genetic origins.
°
Merc ry not detected (detection limit of abo t 100 ppb)
À á #
f ° ° ° ° °
Strong genetic predisposition ànset after environmental ins lt High oidative stress Undermethylation Incomplete brain mat ration
" f °
°
# )) -- Higher concordance in siblings -- 60 to 80% concordance in identical twins | f f f -- Identical twin concordance not 100% -- Major differences in many identical twins.
G g#|+& 1 g f " 4
&#*g: The genetic defect involves a weaened ability to cope with environmental stresses
)fg | | | A tism evident at birth. Greater severity of symptoms. Mental retardation often present.
f Regressive a tism. Symptoms depend on developmental stage d ring ins lt.
# fg | || g$ : u $
% °
2
°
#
P " & f °
C rrent consens s that a tism res lts from many genetic defects, rather than from a single gene.
°
A common factor in these genetic defects may be 1 $ .
* 4 +$ # f ° °
Genetic tendency for depressed GSH, MT, Se, etc at intestinal and blood/brain barriers, Inability to prevent Hg, Pb, Cd, and reactive oygen specie from invading the brain. -- destr ction of brain cells -- interr ption of brain mat ration process
B f+$ # 2
#f ° ° ° ° ° ° °
Hypersensitivity to Hg and other toic metals Hypersensitivity to certain proteins (casein, gl ten, etc) Poor imm ne f nction Disr ption of the methylation cycle Inflammation of the brain & G.I. tract. Depletion of gl tathione & metallothionein Ecessive amo nts of ³ nbo nd´ copper
B f+$ # " | ° ° ° ° °
Destroys digestive enzymes needed to brea down casein & gl ten proteins, Promotes candida/yeast levels, Diminishes Zn levels and prod ction of stomach acid, Prod ces inflammation, Ineffective barrier to toic metals at the intestinal m cosa.
2P g $ P 1. 2. 3. 4. 5. 6. 7.
Chelation with DMSA, DMPS, EDTA, etc. Methyl B-12 Metallothionein Promotion Transdermal or Injected Gl tathione Zn, Se, CoQ-10, Ta rine, Vitamins A,C,D,E Alpha Lipoic Acid Risperdal
2 G ° ° °
What % of a tism cases are triggered by Hg? Can ³old´ Hg stay in the brain and ca se contin ing damage? How serio s is the contin ing daily epos re to Hg from the environment?
+$ # ° ° °
°
DMSA and DMPS are powerf l antioidants. Chelation can provide antioidant benefits even if toic metals are present. For many patients, the primary benefits of chelation res lt from antioidant properties, and not from removal of Hg or other metals. Antioidant benefits from chelation appear to ³fade away´ after abo t 2-4 wees.
P f f °
Rapid removal of toic metals from peripheral soft tiss es & blood, th s preventing their access to the brain,
°
Powerf l antioidant
. f °
° ° °
Does not fi intestinal or blood/brain barriers, rendering the patient v lnerable to f t re toic epos res, Antioidant benefits are temporary, lasting only 2-4 wees, May not remove toic metals from the brain, Complicates Zn management.
Pf ff P ° ° °
Identification & individ alized treatment of biochemical imbalances, MT-Promotion therapy, Selective se of adj nct therapies - CF/GF diet - Normalization of intestinal flora - Methylation therapies - Digestive enzymes - etc.
2P P +C Advances in cognition, socialization, and speech by enhanced development of immat re brain cells and new synaptic connections.
2P # +C ° Elimination of toic metals & ecess C ° Improved imm ne f nction ° Healing of the G.I. tract ° Red ced food sensitivities ° Improved behavior control
2 P ° ° °
Genero s amo nts of Zn and GSH which are essential to ind ction and f nctioning of MT, Seleni m, Vitamins B-6, C, E, which are nown to promote MT, S pplements of the 14 amino-acid constit ents of MT in the proportion they eist in MT proteins.
B ) f2 P ° ° ° °
Directly aimed at development of brain cells & new synaptic connections, Potential for permanently correcting the intestinal and blood/brain barriers, Restores the nat ral (and powerf l) body system for coping with toic metals, Potential for eliminating food sensitivities, yeast problems & intestinal inflammation.
2P ) ° °
°
Pre-loading with zinc is necessary to prevent temporary side effects, B ilding p tolerance to the MT Promoter form lation can be a slow process for some children, Commercial lab testing to determine MT stat s is in its infancy.
f g ) ' #' # D ° ° °
Elimination of toic metals and ecessive oidative stress, Behavioral therapy to stim late development of brain cells and synaptic connections, MT-Promotion therapy to enable completion of brain mat ration.
# ° °
°
àidative stress may be the decisive factor in a tism-spectr m disorders. Treatment protocols aimed at (1) red ction of oidative stresses and (2) development of new brain cells and synapses are highly promising. Long-term antioidant therapy may be needed to prevent loss of brain cells and mental retardation.
&@M+ E
William J. Walsh, Ph.D. Pfeiffer Treatment Center Warrenville, Illinois www.hriptc.org
William J. Walsh, Ph.D. Pfeiffer Treatment Center Warrenville, IL
Pf ff
° ° ° ° ° °
à tpatient medical facility 23,000 patients from all 50 states and 75 foreign co ntries. Collaboration between medical doctors and scientists. Individ alized Biochemical Therapy Scientific Research 501c3 P blic Charity
Pf ff ° ° °
°
Chemistry Database St dies Metallothionein Research àidative Damage -- Essential fats -- Vasc lar tiss e -- Imm ne cells (le ocytes) -- Brain tiss e Assays of a tism/control brain tiss es.
Pf ff ° 10,600 ° ° °
Behavior & ADHD 6,000 A tism 3,700 Schizophrenia & Bipolar 3,600 Depression
Pf ff °
Abo t 90 to 150 assays of chemical factors in blood, rine, or hair for more than 6,000 patients
°
More than 1,000,000 separate chemical analyses
M P f
M ! ° °
" f# $ % & '(% R
° °
°
Major biochemical abnormalities observed thro gho t the a tism spectr m. The biochemical imbalances are more severe than those for ADHD, violent behavior, depression, and psychosis. Female a tistics have more disordered chemistry than male a tistics.
)| ° ° ° ° ° °
Elevated ser m copper Elevated toic metals Depressed zinc Undermethylation Pyrrole disorder Severe oidative stress & damage
° ° ° ° ° ° °
Depressed Methionine and SAMe Elevated SAH and Adenosine High Urinary Isoprostanes Depressed Cysteine and Gl tathione Low Seleni m Levels Depressed Cer loplasmin Elevated Levels of Free-Radicals
g f * +$ #
!
,
f $ $ $ f +$ ) ff
g$ # A tism Spectr m (N=503) Controls (N=25)
Mean C /Zn Ratio 1.63 1.15
t = 8.77 (two-tailed ³t´ test); - American Psychiatric Association Ann al Meeting New àrleans, 2001.
| ff . # P /# 0 ! /À
R
g
1. 2.
3.
Depletes metallothionein & gl tathione Associated with inflammation & ecessive oidative stress Can ca se abnormal ne rotransmitter levels.
.12 . - !
3 ! 3 !
3 3
"
* 2 | 4 ° ° ° °
Req ired for development of brain cells, Primary ³filter´ for Hg, Pb, and other metal toics at intestinal and blood/brain barriers, Req ired for homeostasis of C and Zn, S pports imm ne f nction. " " ! "
# #1# ° °
Short, dense, ndeveloped brain cells, Abnormalities observed primarily where MT levels are highest (amygdala, hippocamp s, P rinje cells, inferior olives, and pineal gland).
R á
f2
f ° ° °
MT-3 assists in the pr ning of brain cells, which maes space for growth of ³new´ cells, MT-1 and MT-2 participate in the nat ral growth (development) of brain cells, MT-3 is the primary agent for termination of growth of f lly-developed brain cells.
1 5 1 2'"# '# 6 25 7 GSH is first line of defense against Hg, Pb, etc, b t has limited capacity for toic metals. ° When > 10% of GSH is bo nd to toic metals, additional toics are transferred from GSH to MT. ° Se increases inetics of the GSH/MT antioidant system by more than 50%. ° For major epos res, most toic metals depart the body bo nd to MT.
°
2 P °
°
°
Form lation of 22 n trients that promote genetic epression or f nctioning of MT, incl ding Zinc, Gl tathione, and Seleni m, Aimed at completion of brain mat ration to enable gains in cognition, speech, and socialization, Has res lted in higher freq ency of a tism recovery at Pfeiffer Treatment Center. # P 8'!,!' 8 9 : '! 8;
+$ )# °
P blished in à # $ ~ <,< <0 A thors Pratico, Walsh, McGinnis, and Yao.
°
Findings: Elevated oidative damage to fats and vasc lar tiss es for a tistic s bjects, compared to controls.
) P. -
P
+$ )#! °
% & & $' ( ) *( (+ g ' 2" '* 'P
'# '.1 '
°
f$ )
°
g f )
| f+$
)# °
Untreated a tism may be ne rodegenerative with oidative damage ca sing slow, grad al loss of brain cells and IQ.
°
Antioidant therapy may be necessary thro gho t the life of a person diagnosed with an a tism spectr m disorder.
g 9 =8' ;f & ) °
Most yo ng ASD patients appear q ite bright
°
Many s ccessf lly treated children become mainstreamed and academic leaders,
°
Most ad lt a tistics ehibit mental severe retardation.
.5# J
, " - R R
! .$ O
! " : f ( )>09!; ,'! ?
.5 )f # ° ° ° ° °
SAMe levels 36% lower, SAMe/SAH ratios 50% lower, Homocysteine 180% higher, Cysteine 40% lower, GSH 25-60% lower.
.5#
g #
P
6 )2 'P '! 7 2 ' ~ 0'& !'2 '! ? W.McGinnis, T.A dhya, W.Walsh, J.Jacson, J.McLaren-Howard, A.Lewis, P.La da, D.Bib s, F.J rna, R.Lietha, A.Hoffer. ° °
! , f# $
P. ) 5 f $
@ A
f P @
9
f ;
<
< <
<
< P
< A
<
<<
fg . ( ° ° °
°
Do ble blind, controlled st dy, 176 brain tiss es & 22 peripheral samples from U. of Maryland¶s A tism Brain Ban, Elemental analysis for 16 elements, incl ding Hg, Pb, C , Zn, and Se sing high-brilliance photons at ANL¶s Advanced Photon So rce), First elemental assays ever attempted for a tism & control brain tiss es.
) # Cerebell m ° S perior Corte ° Deep Corte ° White Matter °
# (/(
# f ) °
Abnormal levels of Ca, S, Fe, Zn in a tism brains,
°
The abnormalities are striingly different for male and female a tistics, s ggesting that male and female a tism may have different genetic origins.
°
Merc ry not detected (detection limit of abo t 100 ppb)
À á #
f ° ° ° ° °
Strong genetic predisposition ànset after environmental ins lt High oidative stress Undermethylation Incomplete brain mat ration
" f °
°
# )) -- Higher concordance in siblings -- 60 to 80% concordance in identical twins | f f f -- Identical twin concordance not 100% -- Major differences in many identical twins.
G g#|+& 1 g f " 4
&#*g: The genetic defect involves a weaened ability to cope with environmental stresses
)fg | | | A tism evident at birth. Greater severity of symptoms. Mental retardation often present.
f Regressive a tism. Symptoms depend on developmental stage d ring ins lt.
# fg | || g$ : u $
% °
2
°
#
P " & f °
C rrent consens s that a tism res lts from many genetic defects, rather than from a single gene.
°
A common factor in these genetic defects may be 1 $ .
* 4 +$ # f ° °
Genetic tendency for depressed GSH, MT, Se, etc at intestinal and blood/brain barriers, Inability to prevent Hg, Pb, Cd, and reactive oygen specie from invading the brain. -- destr ction of brain cells -- interr ption of brain mat ration process
B f+$ # 2
#f ° ° ° ° ° ° °
Hypersensitivity to Hg and other toic metals Hypersensitivity to certain proteins (casein, gl ten, etc) Poor imm ne f nction Disr ption of the methylation cycle Inflammation of the brain & G.I. tract. Depletion of gl tathione & metallothionein Ecessive amo nts of ³ nbo nd´ copper
B f+$ # " | ° ° ° ° °
Destroys digestive enzymes needed to brea down casein & gl ten proteins, Promotes candida/yeast levels, Diminishes Zn levels and prod ction of stomach acid, Prod ces inflammation, Ineffective barrier to toic metals at the intestinal m cosa.
2P g $ P 1. 2. 3. 4. 5. 6. 7.
Chelation with DMSA, DMPS, EDTA, etc. Methyl B-12 Metallothionein Promotion Transdermal or Injected Gl tathione Zn, Se, CoQ-10, Ta rine, Vitamins A,C,D,E Alpha Lipoic Acid Risperdal
2 G ° ° °
What % of a tism cases are triggered by Hg? Can ³old´ Hg stay in the brain and ca se contin ing damage? How serio s is the contin ing daily epos re to Hg from the environment?
+$ # ° ° °
°
DMSA and DMPS are powerf l antioidants. Chelation can provide antioidant benefits even if toic metals are present. For many patients, the primary benefits of chelation res lt from antioidant properties, and not from removal of Hg or other metals. Antioidant benefits from chelation appear to ³fade away´ after abo t 2-4 wees.
P f f °
Rapid removal of toic metals from peripheral soft tiss es & blood, th s preventing their access to the brain,
°
Powerf l antioidant
. f °
° ° °
Does not fi intestinal or blood/brain barriers, rendering the patient v lnerable to f t re toic epos res, Antioidant benefits are temporary, lasting only 2-4 wees, May not remove toic metals from the brain, Complicates Zn management.
Pf ff P ° ° °
Identification & individ alized treatment of biochemical imbalances, MT-Promotion therapy, Selective se of adj nct therapies - CF/GF diet - Normalization of intestinal flora - Methylation therapies - Digestive enzymes - etc.
2P P +C Advances in cognition, socialization, and speech by enhanced development of immat re brain cells and new synaptic connections.
2P # +C ° Elimination of toic metals & ecess C ° Improved imm ne f nction ° Healing of the G.I. tract ° Red ced food sensitivities ° Improved behavior control
2 P ° ° °
Genero s amo nts of Zn and GSH which are essential to ind ction and f nctioning of MT, Seleni m, Vitamins B-6, C, E, which are nown to promote MT, S pplements of the 14 amino-acid constit ents of MT in the proportion they eist in MT proteins.
B ) f2 P ° ° ° °
Directly aimed at development of brain cells & new synaptic connections, Potential for permanently correcting the intestinal and blood/brain barriers, Restores the nat ral (and powerf l) body system for coping with toic metals, Potential for eliminating food sensitivities, yeast problems & intestinal inflammation.
2P ) ° °
°
Pre-loading with zinc is necessary to prevent temporary side effects, B ilding p tolerance to the MT Promoter form lation can be a slow process for some children, Commercial lab testing to determine MT stat s is in its infancy.
f g ) ' #' # D ° ° °
Elimination of toic metals and ecessive oidative stress, Behavioral therapy to stim late development of brain cells and synaptic connections, MT-Promotion therapy to enable completion of brain mat ration.
# ° °
°
àidative stress may be the decisive factor in a tism-spectr m disorders. Treatment protocols aimed at (1) red ction of oidative stresses and (2) development of new brain cells and synapses are highly promising. Long-term antioidant therapy may be needed to prevent loss of brain cells and mental retardation.
&@M+ E
William J. Walsh, Ph.D. Pfeiffer Treatment Center Warrenville, Illinois www.hriptc.org
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