Modulating Glial Fate and Function in Development and Disease

总结 人类中枢神经系统中的1000亿个神经元中有许多需要保护和绝缘 一种叫做髓磷脂的涂层来正常发挥作用。这种髓鞘涂层的丢失或损伤是许多神经系统疾病的基础。 因此，新髓鞘的再生是改善患有疾病的患者健康的重要部分。 多发性硬化症（MS）、视神经肌萎缩症（NMO）和其他髓鞘疾病，如小儿 脑白质营养不良没有髓鞘，某些神经细胞不能正确地传导电脉冲，导致 虚弱、疲劳、视力丧失、认知能力下降和身体机能丧失。我们已经开发出一种新颖 再生的方法，以确定重要的新的潜在治疗髓鞘丢失或 这是建立在我们在干细胞生物学的专业知识。我们的总体目标是利用体外小鼠 和人类干细胞平台，我们已经开发出定义的中央机制， 在所有髓鞘疾病中阻止髓鞘发育和功能。我们寻求发现 可以调节少突胶质细胞的功能或再生的新的治疗干预， 星形胶质细胞恢复髓鞘形成和神经功能。对于多发性硬化症，我们已经定义了一个 刺激髓鞘再生的中枢机制，并确定了可以逆转 瘫痪的小鼠模型。展望未来，我们寻求利用我们的创新技术， 在多发性硬化症中的经验，以确定髓鞘功能障碍的疾病和背景特异性效应物， 为新疗法提供基础。

SUMMARY Many of the 100 billion neurons in the human central nervous system require a protective and insulating coating called myelin to function properly. Loss or damage of this myelin coating underlies many neurological disorders and therefore regeneration of new myelin is an important part of improving health for patients with multiple sclerosis (MS), neuromyelitis optica (NMO), and other myelin diseases such as the pediatric leukodystrophies. Without myelin, certain nerve cells cannot properly conduct electrical impulses, leading to weakness, fatigue, loss of vision, cognitive decline, and physical incapacity. We have developed a novel regenerative approach to identify important new potential treatments for patients with myelin loss or dysfunction that is built upon our expertise in stem cell biology. Our overall goal is to utilize the in vitro mouse and human stem cell platforms that we have developed to define the central mechanisms responsible for preventing myelin development and function across the full range of myelin disorders. We seek to discover novel therapeutic interventions that can modulate the function or regeneration of oligodendrocytes and astrocytes to restore myelination and neurological function. For multiple sclerosis, we have already defined a central mechanism to stimulate myelin regeneration and identified potent small molecules that can reverse paralysis in mouse models of disease. Moving forward, we seek to leverage our innovative technologies and experience in multiple sclerosis to identify disease- and context-specific effectors of myelin dysfunction and provide the basis for new therapies.