Thrombotic Thrombocytopenic Purpura (TTP) Ritesh Karsalia

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

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

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

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

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

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

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

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

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?

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

Testing

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>.