NOVO-118 as a therapeutic to promote remyelination in in vivo models of MS

7.项目总结 多发性硬化症(MS)是一种中枢神经系统髓鞘变性疾病。 被一种自身反应性免疫反应摧毁。这种脱髓鞘伴随着 髓鞘细胞本身，即少突胶质细胞。反复的脱髓鞘使剥离的中枢神经系统 神经元容易退化，是导致神经元功能障碍和神经变性的主要原因 目前批准的治疗多发性硬化症的方法只是旨在减少自身免疫攻击的频率。 并且没有解决重新髓鞘形成的需要。在不诱导重新髓鞘形成以治愈以前的损伤的情况下， 病程只能延缓，但不能逆转。 中枢神经系统含有大量的少突胶质前体细胞(OPC)，它们有可能 分化为成熟的少突胶质细胞，并使剥脱的轴突重新髓鞘。尽管OPC是高效的 被招募到MS皮损中，OPC分化为成熟的少突胶质细胞，随后重新髓鞘形成，是 Novoron女士发现LRP1受体是防止OPC的关键信号分子 差异化。通过利用基因缺失或拮抗来取消LRP1功能，我们可以增加OPC 分化和恢复大脑的再髓鞘能力。 这项建议的目标是从我们的初步数据过渡到我们的新方法 将这项技术发展成一种可行的人类药物。在此阶段1应用程序结束时， Novoron将拥有以下特性：1)具有体内剂量-反应曲线的主要候选药物，2)疾病 在铜试剂脱髓鞘模型中的疗效数据，以及3)在自身免疫中的疾病疗效数据。 介导型EAE多发性硬化模型。这些数据将证明我们治愈多发性硬化症的方法的可行性 和preapre Novoron，用于高效的以商品化为重点的第二阶段应用。

7. Project Summary Multiple sclerosis (MS) is a neurodegenerative disease in which myelin of the central nervous system (CNS) is destroyed by a self-reactive immune response. This demyelination is accompanied by the death of the myelinating cells themselves, the oligodendrocytes. Repeated bouts of demyelination leave the denuded CNS neurons vulnerable to degradation and is the major cause of neuronal dysfunction and neurodegeneration in MS. Current approved therapies for MS are aimed only at lessening the frequency of the auto-immune attack and do not address the need for remyelination. Without induction of remyelination to heal previous lesions, the course of disease can only be slowed but not reversed. The CNS contains a large population of oligodendrocyte precursor cells (OPC) that have the potential to differentiate into mature oligodendrocytes and remyelinate denuded axons. Although OPCs are efficiently recruited into MS lesions, OPC differentiation into mature oligodendrocytes, and subsequent remyelination, is inhibited in MS. Novoron has discovered that the LRP1 receptor is a key signaling molecule that prevents OPC differentiation. By abrogating LRP1 function using either genetic deletion or antagonism, we can increase OPC differentiation and restore the remyelinating capacity of the brain. The goal of this proposal is to transition from our preliminary data demonstrating our novel approach to remyelination to developing this technology into a viable human drug. By the end of this Phase 1 application, Novoron will possess the following: 1) a lead drug candidate with an in vivo dose-response profile, 2) disease efficacy data in the cuprizone chemical demyelinating model, and 3) disease efficacy data in the autoimmune- mediated EAE MS model. These data will demonstrate the feasibility of our approach to healing MS leasions and preapre Novoron for an efficient comercialization-focused Phase 2 application.