Bioprovar Corporation

An Innovative Immune Therapy Targeting the TREM1-INFLAMMATION Pathway to Alleviate Excess Inflammation in Ulcerative Colitis of Geriatric Patients - Abstract One Million Americans Live With Ulcerative Colitis (uc), and 30% of That Population Is Over 60. Thirty-eight Thousand New Cases Are Diagnosed Yearly, With 15% Over 65. More Than a Quarter of Uc Patients Are Aged, and Prevalence in the Over 65 Is Increasing at an Annual Rate of 2.8%. Surgery Treatment Is Risky in Geriatric Patients, and Better Therapy Is Needed. Uc Is an Immune-mediated Disorder of the Colon That Is Debilitating and Not Medically Curable. Extensive Studies Have Shown a Pathogenesis Due to Aberrant Immune Responses to the Intestinal Microbiota, Resulting in Acute and Chronic Inflammations Characterized by Infiltrates of Activated Macrophages (MΦ), Neutrophils (NS), and Lymphocytes, Indicating a Deregulated Activation of the Intestine- Innate Immunity Responder Cells (MΦ and NS). in Uc, Correlating With This Deregulation Is the Unusual Expression of the Triggering Receptor Expressed on Myeloid CELLS-1 (TREM1) on the Intestinal MΦ and the Presence of Activated Platelets Expressing a Ligand for TREM1. TREM1 Is a Potent Activation Receptor of MΦ and NS, and Its Excess Triggering Leads to the Overproduction of Inflammatory Mediators and Excess Inflammation. Two-thirds of Patients Obtain Only Partial or No Benefit From Current Therapies, Specifically Those With MΦ HIGH-TREM1 Expression Sustained Inflammation. Over 1400 Scientific Articles Document the Role of the TREM1-ACTIVATION Pathway (TAP) in Inflammation. We Have Identified TREM1-SV, a Natural Splice Variant and Competitive Inhibitor of TREM1, Which Can Downregulate Tap. TREM1-SV Was Very Efficient at Downregulating Excess Inflammation in Preclinical Sepsis Trials, a Disease Driven by a Deregulated Tap. in Uc, Deregulation of Tap Might Occur From Depletion of TREM1-SV, Ensuing Persistent Activation of Myeloid Cells From Activated Platelets. We Anticipate That Administering TREM1-SV Intravenously or Subcutaneously Will Stop the Excess Inflammation. the Rationale Is That TREM1-SV Downregulates Tap by Competing for the TREM1 Ligands, Thereby Reducing the Number of TREM1-LIGAND Complexes and Avoiding an Excess Triggering Activation of MΦ and NS. Hence, the Intestine Can Recover a Healthy Immunity and Heal. We Aim to Show Therapeutic Efficacy by Conducting Experiments in Which Different Regimens of TREM1-SV Are Administered to Well-established Mouse Models of Chronic Ulcerative Colitis With Altered Innate Immunity. We Use a Custom-made Strain of P. Pastoris to Produce a Batch of Purified Biologically Active Human Recombinant (hu R) TREM1-SV for Animal Treatments. After Induction of Uc, Inflammation Will Be Assessed Before and After Hu RTREM1-SV Treatment With an Established Four-parameter Uc Scoring System and Correlated With Measurements in the Blood of the Inflammatory Cytokine Levels and TREM1-SV Concentration. Neutralization Experiments With an ANTI-TREM1-SV Antibody and Comparative Anti-tnf Therapy Will Be Conducted. We Aim to Produce Innovative Data Demonstrating the Benefit of Hu RTREM1-SV to Downregulate Hyperactive Intestinal Inflammation in Uc. Downregulating Tap With Hu RTREM1-SV Is an Innovative Scientific Approach to Alleviate Excess Inflammation in Uc Patients.