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.

项目摘要 重症肌无力（MG）是一种以肌肉无力为特征的自身免疫性疾病， 自身抗体，主要针对肌肉乙酰胆碱受体（AChR）和肌肉特异性激酶 （MuSK）在神经肌肉接头（NMJ）。这些抗体是由特定的淋巴细胞亚群产生的 但尚未完全表征。由于这个原因，没有MG治疗能够特异性靶向产生MG的细胞。 自身抗体和目前的治疗效果不佳，而且都有副作用， 影响生活质量。尽管是一种罕见的疾病，MG是一种昂贵的疾病， 十亿美元。为了克服这一临床、科学和社会经济挑战，MimiVax提出了 开发一种新的特异性疗法，MV 2C 2抗体，它将靶向特定的细胞亚群， 它们在自身抗体的产生中起着关键作用。具体根除这种 细胞的子集将消除自身抗体的存在，并显着改善体征和症状 大大减少了目前治疗的副作用。收集数据证明 这项创新的技术可行性和临床潜力MimiVax将进行关键的体内研究， 实验MG动物模型，以完成新治疗剂的表征，证实其 特异性，同时了解系统的作用机制和诱导的病理生理变化 此外，将对MG患者的淋巴细胞进行体外研究，以研究MG患者淋巴细胞的细胞和免疫功能。 MV 2C 2 Ab的分子作用机制。最后，MimiVax将继续进行人性化的 MV 2C 2抗体这些活动旨在降低风险并加快第二阶段活动的进程，其中包括 关键的IND前安全性/毒理学、药效学和药代动力学研究， 用于先导试验、IND批准和临床验证。