Approximately 400,000 people with end stage renal disease undergo hemodialysis in the United States each year. During the hemodialysis procedure, the patient's blood circulates through the dialyzer and back to the patient. As a result, the patient's blood encounters the artificial surfaces of the dialyzer and the tubings that connect the patient to the dialyzer. As a result, the complement alternative pathway is activated, causing generation of substantial amounts of C3a and C5a anaphylatoxins. These anaphylatoxins activate neutrophils, monocytes, and platelets, and trigger the inflammatory cascade. NovelMed has developed a monoclonal antibody, which prevents a) C3a, C5a, C5b-9, production, b) neutrophils, monocytes, and platelet activation, and c) TNF-alpha production. In this application, we propose testing the feasibility of using Bikaciomab to prevent the exacerbated inflammatory response that occurs when blood circulates through the dialyzer and associated tubing. Based on current preliminary data, it is clear that Bikaciomab is a novel, target specific, and highly potent drug candidate that would prevent inflammation during dialysis. We believe that such drugs would increase the quality of life for hemodialysis patients.
Public Health Relevance: Approximately 350,000 people with end stage renal disease undergo hemodialysis in the United States each year. In this already compromised patient population, virtually every patient suffers side effects from this hemodialysis procedure at one time or another due to activation of the alternate complement pathway (AP). Bikaciomab blocks the alternative pathway in blood circulating through an extra corporeal blood circulation model of hemodialysis. It is hoped that such an approach will eventually result in improved morbidity and mortality in the patients suffering from End Stage Kidney Failure. Public Health Relevance Statement Page 7
Public Health Relevance Statement: Principal Investigator/Program Director (Last, first, middle): Bansal, Rekha NARRATIVE: Approximately 350,000 people with end stage renal disease undergo hemodialysis in the United States each year. In this already compromised patient population, virtually every patient suffers side effects from this hemodialysis procedure at one time or another due to activation of the alternate complement pathway (AP). Bikaciomab blocks the alternative pathway in blood circulating through an extra corporeal blood circulation model of hemodialysis. It is hoped that such an approach will eventually result in improved morbidity and mortality in the patients suffering from End Stage Kidney Failure. Public Health Relevance Statement Page 7
Project Terms: 2-Propenenitrile, homopolymer; 21+ years old; Adult; Adverse effects; Affinity; Alternative Complement Pathway; Anaphylatoxins; Antibodies; Applications Grants; Area; Attention; Back; Bacterial Infections; Binding; Binding (Molecular Function); Bizzozero's corpuscle/cell; Blood; Blood Circulation; Blood Neutrophil; Blood Plasma; Blood Platelets; Blood Polymorphonuclear Neutrophil; Blood Sample; Blood Segmented Neutrophil; Blood Volume; Blood monocyte; Blood specimen; Bloodstream; C 3-5 Converting Enzyme; C 5b-9; C3 Proactivator; C3 a; C3PA; C3a; C5 a; C5a; C5b-9; CVFBb; Cachectin; Cachectin-Tumor Necrosis Factor; Cells; Childhood; Circulation; Classical Complement Pathway; Clinical; Complement; Complement 3 Proactivator; Complement 3a; Complement 5a; Complement Activation; Complement C3a; Complement C5a; Complement Complex C5b-9; Complement Factor B; Complement Factor B, Alternative Pathway; Complement Membrane Attack Complex; Complement Pathway, Alternative; Complement Protein B; Complement Protein Factor B; Complement Proteins; Consumption; Cytolytic Terminal Complement Complex; Data; Deetjeen's body; Dialysis; Dialysis patients; Dialysis procedure; Dorsum; Dose; Drugs; ESRD; End stage renal failure; End-Stage Kidney Disease; Ensure; Event; Factor B; Generations; Goals; Grant Proposals; Grants, Applications; HOSP; Hand; Hayem's elementary corpuscle; Hemodialyses; Hemodialysis; Heterophil Granulocyte; Hospitals; Host Defense; Human; Human, Adult; Human, General; INFLM; Individual; Infection; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Kidney Failure; Kidney Insufficiency; Lead; Man (Taxonomy); Man, Modern; Marrow Neutrophil; Marrow monocyte; Marrow platelet; Measures; Medical; Medical Directors; Medication; Membrane; Membrane Attack Complex; Methods; Moab, Clinical Treatment; Modeling; Molecular Interaction; Monoclonal Antibodies; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; Neutrophil Activation; Neutrophilic Granulocyte; Neutrophilic Leukocyte; Nylons; PMMA; Pathway interactions; Patients; Pb element; Pharmaceutic Preparations; Pharmaceutical Preparations; Phase; Physician Executives; Plasma; Platelet Activation; Platelets; Poly(methyl methacrylate); Polyamides; Polymethyl Methacrylate; Polymethylmetacrylate; Polymethylmethacrylate; Polymorph; Polymorphonuclear Cell; Polymorphonuclear Leukocytes; Polymorphonuclear Neutrophils; Principal Investigator; Procedures; Production; Programs (PT); Programs [Publication Type]; Properdin Factor B; Properdin Pathway; Proteins; QOL; Quality of life; Recombinant C5a; Recurrence; Recurrent; Renal Disease, End-Stage; Renal Failure; Renal Insufficiency; Reporting; Reproducibility; Research; Reticuloendothelial System, Blood; Reticuloendothelial System, Platelets; Reticuloendothelial System, Serum, Plasma; Running; SC5b-9; SC5b-9 complement complex; SMAC; Sampling; Screening procedure; Serum, Plasma; Staging; Surface; TNF; TNF Alpha; TNF protein, human; TNF superfamily, member 2 protein, human; TNF-2 protein, human; TNF-alpha; TNFA; TNFSF2 protein, human; Terminal Complement Complex; Testing; Therapeutic; Thrombocytes; Time; Toxin; Translating; Translatings; Translations; Treatment Side Effects; Tumor Necrosis Factor; Tumor Necrosis Factor-alpha; Tumor Necrosis Factor-alpha (macrophage-derived); United States; University Hospitals; WHBLOOD; Whole Blood; adult human (21+); bacterial disease; base; clinical applicability; clinical application; complement C5b-9, soluble; complement pathway; complement pathway regulation; cytokine; design; designing; dialysis therapy; drug candidate; drug/agent; efficacy evaluation; efficacy testing; experience; gene product; heavy metal Pb; heavy metal lead; human TNF protein; improved; language translation; member; membrane structure; monocyte; neutrophil; novel; pathway; patient population; pediatric; poly(acrylonitrile); poly(oxy-1,4-phenylenesulfonyl-1,4-phenylene); polyacrylonitrile; polyether sulfone; polyethersulfone; polysulphone; prevent; preventing; programs; public health relevance; screening; screenings; side effect; soluble C5b-9 complex; soluble complement C5b-9; therapy adverse effect; thrombocyte/platelet; treatment adverse effect; tumor necrosis factor, human; tumor necrosis factor-2 protein, human; tumor necrosis factor-alpha promoter allele-2 protein, human
