Vitamin A deficiency: A

Permanent Cure By Emory Sabatini

Photo from: http://commons.wikimedia.org/wiki/File:Carrots_without_stems.JPG

Vitamin A

Essential nutrient for animal life

Good for immune system and overall vision

Found preformed in fruits and vegetables, or in beta-carotene form in orange organics

Created w/in the body when…

Beta-carotene

Oxygen molecule

2 retinal (vitamin A)molecules

With help from Beta-carotene 15,15’-monooxygenase enzyme

Vitamin A deficiency

Happens when not enough vitamin A or Beta-carotene is obtained through diet, so not enough vitamin is found/produced in the body

Symptoms include: Night blindness

Xerophthalmia

Keratomalacia

Permanent blindness

Death

Xerophthalmia – one’s inability toproduce tears due to vitamin Adeificiency (seen internationally)

Photo from: http://en.wikipedia.org/wiki/Subconjunctival_hemorrhage

Deficiency statistics

Is the most common and most deadly (if left untreated) vitamin deficiency in the world

Approx. 250k – 500k children go blind from the deficiency, half of whom die w/in the next year

Most common in Southeast Asia and Africa

Photo from: http://en.wikipedia.org/wiki/Vitamin_A_deficiency

A photo of where the deficiency is mostcommon in the world

Current treatments

Vitamin supplementation – through vitamin A pills or food fortification (adding of nutrients to foods) to force the body to absorb the vitamin

Dietary changes – eating foods high in Vitamin A or beta-carotene

The only problem…

Prenatal vitamins, which are high inVitamin A

None of these solutions are permanent or work in a long term setting!

Photo from: http://en.wikipedia.org/wiki/Prenatal_vitamins

New treatment design

Genetically engineered E. coli (bacteria found in the intestine of humans) to consistently produce beta-carotene

The genes that control the enzymes produced in the several pathways involved in the production of beta – carotene would be inserted into the E. coli

The BCMO1enzyme is produced in the small intestine, so the E. coli would be placed there via oral medication

Bacteria would thrive in the gut and would nourish the host for much longer than vitamin supplementation pills/foods

Biosynthesis Pathways

Glycolysis – the production of Glyceraldehyde 3-phosphate and pyruvic acid from glucose, which are the starting points in the MEP/DOXP pathway

MEP/DOXP – takes G3P and pyruvic acid and produces isopentenyl pyrophosphate and dimethylallyl pyrophosphate

Mevalonate – DMAPP -> geranylgeranyl pyrophosphate

Phytoene Synthase – GGPP -> phytoene -> beta-carotene

Glycolysis PathwayMEP/DOXP Pathway

Mevalonate Pathway

Phytoene Synthase

BETA-CAROTENE!!

Sensors

Vitamin A sensors and beta-carotene sensors would be present in the bacteria to avoid overdose of either substance

Advantages

This is permanent – the host will probably never have to worry about Vitamin A deficiency for the rest of his/her life Most likely…

The host will only have to use this treatment once in their lifetime – a bottle of these pills could supply several families for the rest of their lives Most likely…

But…

While I said this could be permanent and would only have to be taken once…

I don’t know! The bacteria may not live forever in the

gut, but they will thrive longer than vitamin supplementation will keep someone alive

Because of this, the treatment may have to be used periodically in some people

Potential problems

Overdose – while the sensors on the bacteria should be able to control this, overdose is still possible as there is no way to control production while Vitamin A and beta-carotene are not present

Infection – E. coli are harmless in most situations. But, the bacteria should still be prone to antibiotics in case something goes wrong

Photo from: http://en.wikipedia.org/wiki/Escherichia_coli

E. Coli live in the guts of humans, anddo not appear to cause harm in anormal situation. But, they have beenseen to cause food poisoning in somehost bodies.

Testing

Two groups of rats would be tested in a pre-clinical trial

It takes rats approx. 60 days to show signs of vitamin A deficiency. Signs are often seen shortly after deficiency administration is stopped

Symptoms: Xerophthalmia

Growth impairment

Photo from: http://en.wikipedia.org/wiki/Rat

Testing – Group 1

First group: Seeing if treatment design works at all EG: Rats w/ induced deficiency given treatment

design w/ Vitamin A deficient diet

CG: Rats w/ induced deficiency given no treatment w/ Vitamin A deficient diet

SOCG: Rats w/ induced deficiency given vitamin A supplementation w/ Vitamin A deficient diet

ECG: Rats w/ induced deficiency given normal E. coli bacteria w/ Vitamin A deficient diet

PG: Rats w/ induced deficiency given deactivated E. coli w/ Vitamin A deficient diet

Testing – Group 2

Second group: Seeing if sensors can control Vitamin A levels in the body EG: Rats w/ induced deficiency given treatment and

kept on normal diet

CG: Rats w/ induced deficiency given no treatment and kept on normal diet

SOCG: Rats w/ induced deficiency given vitamin A supplementation and kept on normal diet

ECG: Rats w/ induced deficiency given normal E. coli bacteria and kept on normal diet

PG: Rats w/ induced deficiency given deactivated E. coli and kept on normal diet

Testing – Moving on

After the rats have been tested in the different components of the treatment, and the bacteria have been modified to manage problems that arose during testing, the pre-clinical trial would move on to larger animals, and eventually a clinical trial would test humans.

W/ the humans, instead of inducing Vitamin A deficiency, the trial would be conducted in Asia and Africa where the condition is common

With human patients, the trial would have to be closely monitored with government and Internal Review Board approval/oversight

The Future

If the treatment were to be successful, thousands of lives could be saved each year by a simple medication

This treatment could also pave the way for treatments to other deficiency-related conditions, such as vitamin B, C, D, E, and K deficiency

Photo from: http://en.wikipedia.org/wiki/Rickets

Rickets is a disorder of the bones caused by Vitamin D, calciumor phosphorus deficiency

Thank you!!!!!