Translational Development of Glial Growth Factor 2 (GGF2) for the Treatment of St

描述（由申请人提供）：摘要在美国，每年大约有80万人患中风。由于缺乏治疗中风的药物，胶质生长因子2 （GGF2）的发展对促进中风恢复具有重要意义。GGF2也有很宽的治疗窗口期（天），因为它不依赖于神经保护。此外，由于GGF2已经在另一种适应症的临床试验中，生产、配方和毒理学方面的障碍要么已经消除，要么已经大大减少。该应用程序的创新之处在于利用GGF2已经完成的现有开发工作，有效地为中风提供IND。在大量临床前数据的基础上，GGF2将在大鼠大脑中动脉闭塞（MCAO）中风模型中进行剂量优化。研究将探讨剂量频率、延长剂量持续时间和确定影响的持久性。将进行额外的毒理学研究，以确定针对中风的特定剂量方案。GGF2的功效将在使用脑回畸形恒河猴模型的非人类灵长类动物皮质缺血模型中得到证实。该模型强调神经恢复，而不是病灶体积缩小。在缺血后24小时开始给药，在大鼠和猴子的研究中，行为改善将持续至少8周。在恒河猴研究完成后，将向FDA提交IND。

DESCRIPTION (provided by applicant): Abstract Approximately 800,000 individuals suffer a stroke each year in the United States. Development of Glial Growth Factor 2 (GGF2) for promotion of stroke recovery is significant because of the lack of therapeutics to treat stroke. GGF2 also has a very wide treatment window (days) because it is not dependent upon neuroprotection. Additionally, as GGF2 is already in clinical trials for another indication, barries to manufacturing, formulation and toxicology have either been eliminated, or greatly reduced. The innovative aspect of this application comes from leveraging the existing development work that has been completed with GGF2 for another indication to efficiently enable an IND for stroke. Expanding on a significant body of preclinical data, GGF2 dosing will be optimized in a rat middle cerebral artery occlusion (MCAO) stroke model. Studies will explore dose frequency, extended dose duration and determine permanence of effects. Additional toxicology will be performed to enable the specific dose regimen proposed for stroke. GGF2 efficacy will then be confirmed in an established non-human primate model of cortical ischemia using a gyrencephalic rhesus monkey model. This model emphasizes neurorecovery rather than lesion volume reduction. Dosing will begin 24 hours after ischemia and behavioral improvements will be followed for at least 8 weeks in both rat and monkey studies. Following completion of studies in rhesus monkey an IND will be filed with the FDA.