Human Monocolonal Antibodies for CNS Remyelination

描述（由申请人提供）：目前研究的主要目标是选择两种天然存在的人igM抗体之一的最佳重组形式，以进一步开发用于炎症性脱髓鞘疾病（如ms）的临床试验。这些抗体被命名为sHIgM22和sHIgM46，由梅奥诊所的Rodriquez实验室通过筛选单克隆γ病患者的血清库分离出来。这些抗体的分离、克隆和鉴定是第一阶段STTR资助的具体目标的一部分。在SJL/J小鼠的Theiler小鼠脑脊髓炎病毒模型中，该抗体已被证明与少突胶质细胞反应并刺激髓鞘再生。当前拨款的具体目标是：将这些抗体的特征扩展到识别生物学相关抗原，并进一步阐明抗体刺激髓鞘再生的潜在机制。开发一个强大的可扩展的生产系统，适合生产商业和临床供应的抗体。将抗体的测试扩展到其他炎症性中枢神经系统脱髓鞘疾病的模型系统中，并评估抗体的毒理学、药代动力学和ADME特性。

DESCRIPTION (provided by applicant): The primary goal of the current research will be to select the best recombinant form of one of two naturally occurring human igM antibodies demonstrated to stimulate remyelination to further develop for clinical testing in inflammatory demyelinating disease, such as MS. These antibodies, designated sHIgM22 and sHIgM46, were isolated by the Rodriquez laboratory at the Mayo Clinic by screening a bank of sera from patients with monoclonal gammopathy. The isolation, cloning and characterization of these antibodies were part of the specific aims of a Phase I STTR grant. The antibodies have been demonstrated to react with oligodendrocytes and to stimulate remyelination in the Theiler's Murine Encephalomyelitis Virus model in the SJL/J mouse. The specific aims of the current grant will be: Extend the characterization of each of these antibodies to the identification of the biologically relevant antigen and further elucidate the underlying mechanism by which the antibodies stimulate remyelination. Develop a robust scaleable manufacturing system that is suitable for producing commercial and clinical supplies of antibody. Extend the testing of the antibodies into other model systems of inflammatory CNS demyelinating disease and assess the toxicologic, pharmacokinetic and ADME properties of the antibodies.