Stem Cell Therapy and Growth Factor Therapy for ALS

肌萎缩侧索硬化症（ALS）引起运动神经元的变性。腰椎内运动神经元缺失 脊髓的某些区域会导致肢体瘫痪，而颈部呼吸运动神经元的丧失仍然是一个问题。 疾病进展的决定性时刻，导致呼吸衰竭和呼吸机依赖。而 对ALS的致病细胞机制的研究正在产生重要和新颖的见解， 这种方法还没有产生显著改善ALS患者健康的新药。以来 运动神经元死亡的细胞机制可能极其复杂 小分子，我们提出了一个更务实的方法。广泛的长期目标和目的是 保护或恢复运动神经元，通过（i）利用可塑性的内在机制，（ii）提供 营养支持或（iii）使用人胚胎干（hES）细胞的再生。为了实现这些目标，三 高度互动的项目将评估运动神经元的功能和生存在一个完善的大鼠模型， 人症项目1将使用解剖学，生理学和行为学方法来确定精确的 ALS大鼠呼吸的变化，以及该系统内运动神经元的死亡是否 可以通过刺激内源性可塑性来调节。项目2将探讨 干细胞衍生的神经胶质细胞和营养因子如GDNF、IGF-1、VEGF和BDNF的组合可 减少运动神经元细胞死亡并增强ALS大鼠的功能。项目3将使用尖端技术 从hES细胞获得运动神经元并确定它们是否能在ALS大鼠中存活的方法 并与肌肉建立新的联系。关于生长因子各自作用的问题， 星形胶质细胞和运动神经元在运动神经元变性的病理将不断解决 在这个项目中。派兄弟是呼吸神经生物学领域的知名研究人员， 人胚胎干细胞、生长因子和hES细胞。他们将协同工作，分享成果和想法 并朝着P01补助金的共同目标前进。这项研究直接涉及的主要目标， NIH：即，将获得有关特定不治之症的基本知识，这些疾病将对 患者的健康。此外，所采取的许多方法与治疗直接相关 干细胞移植是治疗这种毁灭性疾病的真实的未来可能性。

Amyotrophic lateral sclerosis (ALS) causes degeneration of motor neurons. Motor neuron loss within lumbar regions of the spinal cord leads to limb paralysis while loss of cervical respiratory motor neurons remains a defining moment in disease progression, leading to ventilatory failure and ventilator dependence. While investigations of pathogenic cellular mechanisms that underlie ALS are yielding important and novel insights, this approach has not yet produced new drugs that significantly improve the health of ALS patients. Since the cellular mechanisms of motor neuron death may be extremely complex and difficult to block with a single small molecule, we propose a more pragmatic approach. The broad long term objectives and aims are to protect or restore motor neurons by either (i) harnessing intrinsic mechanisms of plasticity, (ii) providing trophic support or (iii) repacement using human embryonic stem (hES) cells. To achieve these aims, three highly interactive projects will assess motor neuron function and survival in a well established rat model of ALS. Project 1 will use anatomical, physiological and behavioral approaches to determine the precise changes in respiration that occur in the ALS rat, and whether the death of motor neurons within this system can be modulated through stimulation of endogenous plasticity. Project 2 will explore whether a combination of stem cell derived glial cells and trophic factors such as GDNF, IGF-1, VEGF and BDNF can reduce motor neuron cell death and enhance function in the ALS rat. Project 3 will use cutting edge methods of deriving motor neurons from hES cells and establish whether they can survive in the ALS rat spinal cord and make new contacts with muscle. Questions regarding the respective roles of growth factors, astrocytes and motor neurons in the pathology of motor neuron degeneration will be constantly addressed throughout this project. The Pi's are established researchers in their fields of respiratory neurobiology, human fetal stem cells, growth factors and hES cells. They will work synergistically, share results and ideas and move towards the common goals of this P01 grant. This study directly addresses the major goal of the NIH: i.e. essential knowledge will be gained about a specific incurable disease that will have an impact on the health of patients. Furthermore, many of the approaches taken have direct relevance to treatment strategies as transplantation of stem cells is a real future possibility for this devastating disorder.