1. Vitamin A deficiency: A Permanent Cure Vitamin A deficiency: A Permanent Cure By Emory Sabatini Photo from: http://commons.wikimedia.org/wiki/File:Carrots_without_stems.JPG

2. 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… 2 retinal (vitamin A) molecules

3. 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 to produce tears due to vitamin A deificiency (seen internationally) Photo from: http://en.wikipedia.org/wiki/Subconjunctival_hemorrhage

4. 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 most common in the world

5. 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 in Vitamin A None of these solutions are permanent or work in a long term setting! Photo from: http://en.wikipedia.org/wiki/Prenatal_vitamins

6. 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

7. 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

8. Glycolysis Pathway MEP/DOXP Pathway Mevalonate Pathway Phytoene Synthase BETA-CAROTENE!!

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

10. 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…

11. 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

12. 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, and do not appear to cause harm in a normal situation. But, they have been seen to cause food poisoning in some host bodies.

13. 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

14. 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

15. 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

16. 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

17. 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, calcium or phosphorus deficiency

18. Thank you!!!!!