Presents

Paddy Jim Baggot MD

International Foundation Genetic Research/ Michael Fund Guadalupe Medical Center, Los Angeles CA

How I got here ?

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

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

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

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

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

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

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

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

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

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

Our Michael Fund Research Is Ongoing

Re-imagine Down Syndrome as a problem in

brain growth and development

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)

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

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

Practical Neuroembryology
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 dont 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

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

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

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

Early infant parent survey

Survey of Parents after Doman style early education How is your child doing? (Normal children)

Excellent

Good

Fair

Poor

Socially Reading

Math
Physical

74% 88% 77% 66%

21% 10% 19% 29%

5% 0.1% 3% 4%

0.3% 0.03% 1% 1%

Unfortunately, no controls

If children can read by the age of three

Permanently enhanced academic performance

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

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

Hormones and Development

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

Breastfeeding
Increased bonding benefits brain development Contains DHA- enhances vision, neuro performance

Prevents thirty diseases in babies (immunoglobulins)

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

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

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

A Therapeutic Trial
It will be difficult and expensive to do it right

It will be useless to do it wrong

IRB pending

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

Hope not scientific evidence

Crawling on day 2
http://www.youtube.com/watch?v=M1v4oYLIvtE&feat

ure=youtu.be

Hope not scientific evidence

Crawling on day 2
http://www.youtube.com/watch?v=M1v4oYLIvtE&feat

ure=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

Hope not scientific evidence

Crawling on day 2
http://www.youtube.com/watch?v=M1v4oYLIvtE&feat

ure=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

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