Thalassemia research project

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Beta Thalassemia

Transcript of Thalassemia research project

  • 1. Anemia and Symptom Alleviation of Beta Thalassemia Principal investigator: Veronica Rohan San Diego, CA (818)689-0476

2. Overview Introduction to Thalassemia and - Thalassemia Problem and Purpose Previous research Hypothesis Method Anticipated results and discussion Materials and budget References 3. What is Thalassemia? Thalassemia is a genetic blood disorder that causes the body to have less hemoglobin than normal resulting in fewer healthy red blood cells, making the people with this disorder anemic. Normal hemoglobin has four protein chains-two alpha globin and two beta globin There are two major types of thalassemia, alpha and beta, named after defects on these protein chains. 4. -Thalassemia One gene from each parent are needed to make enough beta globin protein chains in the body. Beta thalassemia occurs if one or both genes from your parents are altered, causing a defect in the beta protein. 5. Symptoms of - Thalassemia Nearly all thalassemia sufferers are mildly to severely anemic. Anemia symptoms are fatigue, pale skin, fast or irregular heartbeat, shortness of breath, chest pain, dizziness, and cold hands/feet. Beta thalassemia intermedia Slowed growth and delayed puberty Bone problems that may cause bone marrow to expand, causing brittle bones An enlarged spleen, which worsens anemia Beta thalassemia major Pale and listless appearance Poor appetite Dark urine, a sign that red blood cells are breaking down Jaundice Symptoms from intermedia thalassemia 6. Why cant you use iron supplements? Iron supplements are typically prescribed to people with low iron anemia, which may be accidentally diagnosed as opposed to thalassemia Iron supplements have no effect on Thalassemia. In fact, if a thalassemia sufferer has too much iron in the blood from supplementing, it can cause too much iron to build up in the blood stream 7. Problem and Purpose Currently the only concrete form of therapy for thalassemia is blood transfusions, usually in combination with iron chelation therapy. Red blood cells only live for 120 days, so for severe sufferers repeated transfusions are necessary. The purpose of this project is to try and widen the time frame between blood transfusions by alleviating anemia. 8. Previous Research We currently know that adding Folic Acid to the diet helps build healthy red blood cells. This is used as a supplement when receiving transfusions. Research has been shown that adding a high level of Mg to the diet will significantly improve anemia. 9. Hypothesis Supplementing the diet of a beta thalassemia sufferer with both Magnesium and Folic Acid will alleviate symptoms of anemia and reduce the number of blood transfusions needed in their lifetime. 10. Method 1. Mice separated into 3 groups of 10 mice each. Essentially two controls (one group Mg alone, one group FA alone), and one group receiving both Mg and FA. 2. Prior to supplementation, the mice will have 200 microliters of blood drawn for blood testing. a. Blood will be drawn from the dorsal pedal vein via syringe, ensuring the mouse will not need to be sedated. b. The blood drawn will be measured using the automated analyser. The analyser will measure the number of red blood cells to determine level of anemia, the serum level in the blood, and cell dehydration. 3. Control group 1 will receive 65 mcg/day of folic acid. Control group 2 will receive 1000 mg/kg body weight of Mg. The experimental group will get both the folic acid and Magnesium in the same amount as the controls. a. Dosages of supplement will be given by subcutaneous injection. The supplement will be dissolved sterile water before injection in the sterile hood. 11. Method Continued 5. During the initial 3 months of testing, blood in the same units as initial tests will be drawn once weekly to monitor the blood levels. a. The red blood cell count, serum, and cell dehydration levels will all be measured on these blood draws. 6. The weekly blood draws and levels will be recorded, including the time and which mouse the blood came from. 7. After the initial 3 months of trials, the blood draws will reduce to once every two weeks for 3 months, and results at that point may be evaluated to continue research with different combinations. a. To ensure there are no adverse effects of the high dosages of supplement, research will continue after the initial 3 months, totalling 6 months. 12. Results and Discussion Anticipated result is that the combination of Mg and FA will reduce the anemia more than supplementing individually. This ultimately will lessen the side effects of the thalassemia, and reduce the number of transfusions required. 13. Materials 30 mice homozygous for beta thalassemia. Animals between 4-6 months old when obtained, females weighing 25-28 g and males weighing 28 to 30g Equipped wet lab with sterile hood for mixing injections Syringes for blood draw from dorsal pedal vein and for subcutaneous injection Housing for mice: including bedding, food dish, water bottle, and running wheel. Automated analyser to measure blood level Drugs & Chemicals: NaCl, KCl, folic acid, ouabain, bumetanide, 3(N-morpholino) propanesulfonic acid (MOPS), choline chloride, and Acationox, MgCl2 , dimethylsulfoxide, sulfamic acid, phthalate esters. Sterile water for injection 14. Budget 1. $3,300 for aprox. 4-10 mice ($12,300 total cost) 2. $15,000 per month for wet lab rental with sterile hood 3. $1,800 per month for a personal workstation in the lab 4. $2,900 for automated analyser to measure blood level 5. $21,000 per month for principal investigator 6. $30,000 for all drugs, chemicals, and syringes 7. $5,400 for all mouse housing, bedding, and food Total Cost For 6 Months $102,500 15. Acknowledgements Maureen Paolini The Paolini Lab Dr. Estralita Martin Dr. Michael Leboffe Dr. Jeff Holloway Esteban Vazques-Hidalgo Megan Malone Thank You! 16. References 1. Beuzard, Y., Brugnara, C., & Franceschi, L. D. (1997, January 1). Dietary Magnesium Supplementation Ameliorates Anemia in a Mouse Model of -Thalassemia. . Retrieved July 20, 2014, from 2. Mojtahedzadeh, F., Kosaryan, M., Mahdavi, M., & Akbari, J. (2006, January 1). THE EFFECT OF FOLIC ACID SUPPLEMENTATION IN BETA- THALASSEMIA MAJOR: A RANDOMIZED PLACEBO- CONTROLLED CLINICAL TRIAL. . Retrieved July 20, 2014, from 3. Hoff, J. (2000, September 19). Methods of Blood Collection in the Mouse. . Retrieved July 20, 2014, from http://www.lawte. org/materials/hoff.pdf 4. How Are Thalassemias Treated?. (2009, January 1). - NHLBI, NIH. Retrieved July 20, 2014, from http://www.nhlbi.nih. gov/health/health-topics/topics/thalassemia/treatment.html 5. JAX Mice Database - 000996 B6.D2-Hbb/BrkJ. (2011, March 10). JAX Mice Database - 000996 B6.D2-Hbb/BrkJ. Retrieved July 20, 2014, from 6. Halliday, J. (2013, January 1). Life Science Business Incubator. . Retrieved July 20, 2014, from http://muincubator. com/downloads/Lease%20Rate%20Insert.pdf 7. Automatic hematology analyzer BC-5800 Mindray. (2013, September 1). Automatic hematology analyzer. Retrieved July 20, 2014, from 8. Buerge, T., & Weiss, T. (2007, January 1). Handling and Restraint. . Retrieved July 20, 2014, from http://www.usp. br/bioterio/Artigos/Procedimentos%20experimentais/Handling-3.pdf 9. Nesting Materials. (2014, January 1). Lab Animal. Retrieved July 29, 2014, from http://www.pharmaserv. net/enrich_nesting.asp 10. Beta thalassemia. (2009, July 1). Genetics Home Reference. Retrieved July 20, 2014, from http://ghr.nlm.nih. gov/condition/beta-thalassemia 17. Thank you to everyone from Bridges!!