MV2C2 antibody as a new therapeutic for Myasthenia Gravis

MV2C2 抗体作为重症肌无力的新疗法

• 批准号: 10546538
• 负责人: Michael J. Ciesielski
• 金额: $ 46.4万
• 依托单位: MIMIVAX, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546538
• 关键词: Adrenal Cortex Hormones; Adverse effects; Affect; Affinity; Animal Model; Animals; Antibodies; Antibody Affinity; Antibody Therapy; Antigens; Apoptotic; Autoantibodies; Autoimmune; Autoimmune Diseases; B-Lymphocyte Subsets; B-Lymphocytes; Binding; Biochemistry; Blood specimen; Capital; Cells; Centers for Disease Control and Prevention (U.S.); Cholinergic Receptors; Clinical; Clinical Treatment; Clinical Trials; Complement; Data; Development; Disease; Doctor of Philosophy; Drug Kinetics; Epitopes; Experimental Autoimmune Myasthenia Gravis; Flow Cytometry; Foundations; Functional disorder; Future; Goals; Health; Health Care Costs; Healthcare; Hospitalization; Human; Immune; Immunology; Immunotherapy; In Vitro; International; Knowledge; Life; Lymphocyte; Lymphocyte Subset; MUSK gene; Mediating; Molecular Mechanisms of Action; Monoclonal Antibodies; Mus; Muscle; Muscle Weakness; Myasthenia Gravis; National Institute of Neurological Disorders and Stroke; Neurology; Neuromuscular Junction; Neuromuscular Junction Diseases; Pathogenicity; Pathology; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Phase; Phenotype; Pilot Projects; Plasma Cells; Play; Population; Preparation; Procedures; Production; Proteins; Protocols documentation; Quality of life; Rare Diseases; Risk; Role; Safety; Savings; Seeds; Severities; Signs and Symptoms; Small Business Innovation Research Grant; Specificity; System; Therapeutic; Therapeutic Agents; Therapeutic Effect; Thinness; Time; Toxicology; Translating; Transplantation; Universities; Vaccines; Validation; Washington; autoreactive B cell; bone; cell type; clinical practice; comorbidity; cost; curative treatments; cytotoxicity; experience; gastrointestinal; improved; in vivo; infection risk; innovation; mouse model; neonatal Fc receptor; nervous system disorder; neuromuscular transmission; novel therapeutics; pharmacokinetics and pharmacodynamics; pilot trial; pre-clinical; prototype; side effect; socioeconomics; survivin; tool

PROJECT SUMMARY Myasthenia gravis (MG) is an autoimmune disorder characterized by muscle weakness, and caused by autoantibodies, mainly targeting the muscle acetylcholine receptor (AChR) and the muscle specific kinase (MuSK) in the neuromuscular junction (NMJ). These antibodies are produced by a specific subset of lymphocytes yet not fully characterized. For this reason, no MG treatment is able to specifically target the cells producing autoantibodies and current treatments are poorlyeffective and uniformly have adverse effects, which negatively impact quality of life. Despite being a rare disease, MG is a costly one with a hospitalization expense of half a billion dollars per year. To overcome this clinical, scientific and socio-economic challenge MimiVax proposes the development of a new specific therapy, the MV2C2 antibody, that will target the specific subset of cells proving that they are the ones playing a critical role in the production of autoantibodies. The specific eradication of this subset of cells will eliminate the presence of autoantibodies and significantly improve the signs and symptoms of the disease reducing dramatically the adverse effects of the current therapies. To collect data proving the technical feasibility and the clinical potential of this innovation MimiVax will perform pivotal in vivo studies on experimental MG animal model to complete the characterization of the new therapeutic agent confirming its specificity whilst understanding the system in mechanism of action and the pathophysiological changes induced by it. Furthermore, in vitro studies on MG patients’ lymphocytes will be performed to investigate the cellular and molecular mechanism of action of the MV2C2 Ab. Finally, MimiVax will proceed with the humanization of the MV2C2 Ab. These activities aim to de-risk and accelerate the path towards the Phase II activities that include critical pre-IND safety/toxicology, pharmacodynamics, and pharmacokinetics studies that will pave the way towards pilot trials, IND approval and clinical validation.

项目总结