Thrombotic Thrombocytopenic Purpura ( TTP )

1. Thrombotic Thrombocytopenic Purpura (TTP) Ritesh Karsalia

2. What is TTP? • Blood disorder leading to formation of unnecessary blood clots • Based on ADAMTS13 gene • Rare: ≈ 1.7 – 11 humans/million/year • Can be either inherited or acquired ADAMTS13 gene at cytogenetic location 9q34

3. Effects of TTP • Blood vessel blockage • Hemolytic anemia (RBC degradation) • Neurological/Cardiovascular problems • Thrombocytopenia: leads to purpura • Kidney failure Purpura

4. Comparison between different types Normal Inherited (≈20 – 30%) Acquired (≈70 – 80%)

5. Competing Technologies • Plasmapheresis – transfusion of plasma • Very temporary, requires constant repetition, expensive • Severe cases require additional immunosuppressant drugs • Most treatments cost many thousands of dollars and there is no definitive/permenant cure

6. My Design • Alleviates affects of the disease – not a direct cure

7. My Design • Bacteria inserted into bloodstream • No specific species right now because the idea of bacteria living in bloodstream is still being researched • Researchers have found evidence for the existence of bacteria in healthy human blood

8. Expected Results • Anti-ADAMTS13 Antibodies → Anti-ADAMTS13 Receptors → Production of ADAMTS13 Enzymes • Truth table • Overall effect: allow for proper cleavage of von Willebrand factors, leading to no unnecessary blood clots

9. Advantages • A relatively simple solution • Daily plasmapheresis vs. bacteria ingestion • Effectively fights associated effects of TTP • Potential to be cheaper

10. Potential Problems • Bacteria surviving in bloodstream? • More research would be needed to determine which species of bacteria is compatible with design • When would the patient have to ingest new bacteria? • Rate of autoantibodies vs. enzyme production • Multiple enzymes created per detection, but… • What if immune system produces too many autoantibodies?

11. Testing • Test modified bacteria that also has the code for making a color producing protein (GFP) • Place test bacteria in solution of anti-ADAMTS13 antibodies • Process would reveal if bacteria can keep up with the rate of enzyme restriction by anti-ADAMTS13 antibodies

12. Testing

13. Works Cited • "ADAMTS13 Gene." Genetics Home Reference. Web. 31 July 2014. <http://ghr.nlm.nih.gov/gene/ADAMTS13>. • Cantwell, Alan, Dr. "All Human Blood Is Infected with Bacteria." Rense. Web. 31 July 2014. <http://www.rense.com/general77/dblooder.htm>. • Domingue, Gerald J., and Jorgen U. Schlegel. "Novel Bacterial Structures in Human Blood: Cultural Isolation." Infection and Immunity 15.2 (1977): 621-27. Web. 31 July 2014. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC421412/pdf/iai00206-0279.pdf>. • Galbusera, Miriam, Marina Noris, and Giuseppe Remuzzi. Inherited Thrombotic Thrombocytopenic Purpura. National Center for Biotechnology Information. Web. 31 July 2014. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2635388/pdf/0940166.pdf>. • Mclaughlin, R. W., H. Vali, P. C. K. Lau, R. G. E. Palfree, A. De Ciccio, M. Sirois, D. Ahmad, R. Villemur, M. Desrosiers, and E. C. S. Chan. "Are There Naturally Occurring Pleomorphic Bacteria in the Blood of Healthy Humans?" Journal of Clinical Microbiology 40.12 (2002): 4771-775. Web. 31 July 2014. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC154583/#r7>. • "Thrombotic Thrombocytopenic Purpura." Genetics Home Reference. Web. 31 July 2014. <http://ghr.nlm.nih.gov/condition/thrombotic-thrombocytopenic-purpura>. • "Thrombotic Thrombocytopenic Purpura." Wikipedia. Wikimedia Foundation, 24 July 2014. Web. 31 July 2014. <http://en.wikipedia.org/wiki/Thrombotic_thrombocytopenic_purpura>. • "What Is Thrombotic Thrombocytopenic Purpura?" National Heart, Lung, and Blood Institute. Web. 29 July 2014. <https://www.nhlbi.nih.gov/health/health-topics/topics/ttp/>. • Willacy, Hayley, Dr., and Colin Tidy, Dr. "Thrombotic Thrombocytopenic Purpura." Patient. Web. 31 July 2014. <http://www.patient.co.uk/doctor/thrombotic-thrombocytopenic-purpura>.