New Directions For Down Syndrome Research. Paddy Jim Baggot M.D.

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

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

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 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

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

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

Increased bonding benefits brain development

Contains DHA- enhances vision, neuro performance

Prevents thirty diseases in babies (immunoglobulins)

Breastfeeding

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&feature=youtu.be

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

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

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