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Presents
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Paddy Jim Baggot MD
International Foundation Genetic Research/ Michael Fund
Guadalupe Medical Center, Los Angeles CA
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How I got here ?
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Down syndrome-trisomy 21 Common cause of mental retardation- IQ= 25-75
One extra chromosome 21 : three instead of two
One extra copy of each gene on X21- Gene dosage effect
50% increase in gene products, enzymes
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Child with Down Syndrome
The child with Down syndrome excels in one way:
The ability to love and be loved
Such children love unconditionally
This is one of their greatest contributions to humanity
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Down Syndrome:
Re-Imagine Problem
No silver bullet for Down syndrome
But many small improvements over the years
Ear checks, eye checks, thyroid treatment,
Infant stimulation
Improved neurologic performance
Many small improvements, improved infant
health, neurologic performance, life span
one candle
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Amniotic Fluid Folic acid Is folic acid (a B vitamin) a problem in Down S ?
Folic,B12, B6-Monocarbons-DNA, RNA, Proteins, NTs
Monocarbons impaired-increased MCV, MTX sens.
Folate marker (FIGLU) increased in folate deficiency
Amniotic fluid: FIGLU decreased-No Folate deficiency
It was decreased by gene dosage effect:
The gene was on chromosome 21
First paper on biochemical metabolism of DS in fetus
Baggot et al, Fetal Diagnosis and Therapy, 2006
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Amniotic Fluid
Vitamin B2 Elevation Vitamin B2 deficiency markers
Suggests DS fetuses are deficient of vitamin B2
Does vitamin B 2 affects brain function? Yes
First paper to find a correctable problem in DS
fetus
This finding requires confirmation
Baggot et al, Fetal Diagnosis and Therapy, 2008
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Amniotic Fluid Vitamin B6 Children with Down syndrome have increased
oxalate- a vitamin B6 deficiency marker
Mild neuro improvements with vitamin B6
B6 necessary to convert Tryptophan to serotonin
Down syndrome fetuses have elevated oxalates
It suggests fetuses with DS also deficient of B6
A second correctable problem in fetuses
This finding requires confirmation
Baggot et al, Fetal Diagnosis and Therapy, 2008
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Amniotic Fluid
Carbohydrates (Sugars)
In other genetic diseases mental retardation
could result from disturbances of sugars
Our data- No major sugar problems in Down
syndrome
Baggot et al, Internet Journal of Gynecology and
Obstetrics, 2007
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Amniotic Fluid cystathionine beta synthase (Homocysteine) Cystathionine Beta synthetase Gene on chromosome 21-
Serine + Homocysteine-> cystathionine->cysteine
Serine decreased, cystathione, cysteine increased
Consistent gene dosage effect
Homocysteine increased
If folate and B12 deficiency absent then
Suggests Vitamin B6 deficiency (again)
In preparation
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Biotin-Related metabolites Holocarboxylase synthase chromosome X21
Converts biotin to active form-holocarboxylase
Function of biotin is to add carboxylate groups (RCO2H)
Markers of biotin deficiency would fall – they did
Thus gene dosage effect confirmed
Would simulate biotin excess
Biotin safe at 1000X RDA
Baggot et al, in preparation
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What Have We Learned? Potentially correctable problems in DS fetuses
Treatment could begin before birth
In past, some said vitamins were beneficial
Others claimed vitamins were worthless
Most Studies on older children, adults
Maybe timing was missed by both
Maybe treatment should begin before birth
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Our Michael Fund
Research Is Ongoing
Re-imagine Down Syndrome as a problem in
brain growth and development
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Re-Imagine Down
Syndrome: Brain Growth Down syndrome a problem of brain development
Different causes of mental retardation have
similar micropathology -dendrites
Intelligence depends on how brain develops in
late pregnancy/early childhood
Dendrites (Branches)
Synapses (Intersections)
Subcellular processes (Leaves)
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Brain Cells Are Like Trees Think of a brain cell as a Tree.
Tree branches are called Dendrites.
These receive information from other cells
Leaves are called terminal boutons.
These are contact points with other brain cells
A contact between two brain cells is synapse.
Nucleus is control center of cell.
Tree trunk is the axon.
Information goes out on axon to other brain cells.
This analogy developed by brain researcher Marion Diamond in Magic Trees of Mind
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Brain Cells Grow Like Trees
Trees need water and fertilizer for growth
Brain cells need nutrition to grow and develop
Trees could be inhibited by herbicides/toxins
Brain cells can be stunted or killed by toxins
Tree growth influenced by presence of light
Brain cells grow and develop with education
In absence of light, leaves will fall
Limited education – limited brain development
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Brain circuit diagram- bigger than a university
An ingenious solution by Creator
Make twice as many brain cells –lose those unused
Many extra glia (helper cells) – lose those unused
Many dendrites – lose those unused
Many synapses lose those unused
Many cells, dendrites, connections normally lost in
brain development
If you don’t use it, you lose it
If you do use it, you keep it, and grow it
Use & grow your brain-like exercise & muscle
Brain: unique container-more you add/more it
holds
Practical Neuroembryology
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Education
Is Not Just Knowledge Education changes the structure of the brain
Just as light would change structure of a tree
Education and experiences shine light on the
“trees”-grow the dendrites, and synapses
Practical ways to enhance brain development
We all know this
Olympic skaters
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Learning before birth Learning should begin before birth
Songs learned before birth remembered decades
Cultures with prenatal learning-China, Korea, Africa
The Kick game-1.) say “kick” when baby kicks
2.) later baby will kick when mother commands “kick”
Prenatal Music enhanced postnatal motor development
Talk- Read- Count- Sing- Dance with your fetus
Van De Carr F Rene and colleagues
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Early infant education Promoted by Glen Doman and others
Methods to teach infants (beginning 0-3 months)
Physical exercise especially crawling from birth
Passive/active Balance/vestibular training
Reading - sight words large red letters
Math-count large red dots
Methods adapted to infant capabilities
3 month answering questions logically with choice board
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Early infant parent survey Survey of Parents after Doman style early education
How is your child doing? (Normal children) Excellent Good Fair Poor N
Socially 74% 21% 5% 0.3%
Reading 88% 10% 0.1% 0.03%
Math 77% 19% 3% 1%
Physical 66% 29% 4% 1%
Unfortunately, no controls
If children can read by the age of three
Permanently enhanced academic performance
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THE BRAIN AND NUTRITION
Brain needs nutrients for function and development
Very few adults or fetuses have overt deficiencies
But mild deficiencies common
Mild deficiencies frequent in pregnant women
Fetuses and infants grow much faster than adults
Thus nutrition more important at younger age
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BRAIN AND TOXINS Toxins are part of modern life-
Lead was removed from gasoline to help children
Toxins often affect brain function and development
HUNDREDS of neurotoxins found in all adults, and
in fetal amniotic fluid, umbilical cord blood
These problems could be improved
We could reduce brain toxin exposure in fetuses
Any fetus could benefit from brain toxin reduction
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maternal thyroid hormone and infant intelligence
Use of progesterone becoming more common in
pregnancy to prevent pre-term labor
Older literature -K Dalton- improved long term
neurologic development after prenatal progesterone
M Diamond-enhanced rat brain development with
progesterone-6% increase Cerebral Cortex thickness
Hormones and Development
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Increased bonding benefits brain development
Contains DHA- enhances vision, neuro performance
Prevents thirty diseases in babies (immunoglobulins)
Breastfeeding
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Pierre Marois, Hyperbaric oxygen therapy, (HBOT), & Cerebral Palsy
Dr. P Marois, @ Hospital Ste Justine Montreal Canada
Treated 1000 cerebral palsy patients (HBOT) most improved
250 patients published in 3 trials , one in the Lancet
In general, improved spasticity, gross and fine motor, cognition, language, attention and communication
Often substantial improvement
Proposed mechanisms: reactivation of “idling” neurons, improved blood flow (SPECT Scan), increased stem cells
Senechal C, Larivee S, Engelbert R, Marois P 2007.
J Am Assn Phys Surg 12:(4) : 109-113
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Down Syndrome and HBOT Case of Emily 9 (Pierre Marois)
In 5 cases, children with Down syndrome were treated
Other parents reported substantial improvement
Seven year old Down syndrome female
Function: 2.5 y/o on Peabody motor developmental survey
Received 40 treatments HBOT, 1.3 ATM @ 28% oxygen
After 2 months treatment, gained one year of development
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Proposed Five-Square Program
Education before birth
Education after birth
Biomedical treatment before birth
(Nutrients, drugs, toxins, hormones, HBOT)
Biomedical treatment after birth
Breastfeeding
Not specific for Down Syndrome
Other diagnoses—
Normal children
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A Therapeutic Trial
It will be difficult and expensive to do it right
It will be useless to do it wrong
IRB pending
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A case of Hope-but not DS Mother had a major cardiac problem
LV Non Compaction-arrhythmnias , syncope , CHF earlier
Some told her not to get pregnant or to abort
Some doctors were reluctant to participate in her care
She was 44, but normal baby, no cardiac complications
Before birth-english and chinese, mother and father
In womb, Baby kicked on command, English or Chinese
The baby crawling on second day of life
Baby learned chinese song in womb -father sang it
When postnatal baby heard song, responded with smile
Developing Fetuses –more faculties than we think
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Hope not scientific evidence Crawling on day 2
http://www.youtube.com/watch?v=M1v4oYLIvtE&feature=youtu.be
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Hope not scientific evidence Crawling on day 2
http://www.youtube.com/watch?v=M1v4oYLIvtE&feature=youtu.be
Newborns could normally crawl
Smiling when hear song heard as fetus
http://www.youtube.com/watch?v=r9q_VAAs-A4
Babies could do more and learn more than we expect
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Hope not scientific evidence Crawling on day 2
http://www.youtube.com/watch?v=M1v4oYLIvtE&feature=youtu.be
Newborns could normally crawl
Smiling when hear song heard as fetus
http://www.youtube.com/watch?v=r9q_VAAs-A4
Babies could do more and learn more than we expect
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THANK YOU THANK YOU FOR YOUR ATTENTION
Thank you for your help
Thank you for your prayers
Thank you for publicizing this work
Thank you for your donations to the Michael Fund:
International Foundation for Genetic Research
The Michael Fund
4371 Northern Pike
Pittsburgh PA 15146
www.michaelfund.org