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，每年约有80万人中风。由于缺乏治疗中风的药物，开发胶质生长因子2(GGF2)促进中风康复具有重要意义。GGF2也有非常宽的治疗窗口(天数)，因为它不依赖神经保护。此外，由于GGF2已经在进行另一种适应症的临床试验，制造、配方和毒理学方面的障碍要么已经消除，要么大大减少。此应用程序的创新方面来自于利用GGF2完成的现有开发工作，作为另一种指示，有效地支持IND用于中风。在大量临床前数据的基础上，GGF2的剂量将在大鼠大脑中动脉闭塞(MCAO)中风模型中得到优化。研究将探索剂量频率、延长的剂量持续时间并确定效应的持久性。将进行额外的毒理学检查，以实现建议用于中风的特定剂量方案。GGF2的有效性随后将在已建立的非人类灵长类皮质缺血模型中得到证实，该模型使用的是脑回猕猴模型。这种模式强调神经恢复，而不是缩小病变体积。给药将在缺血后24小时开始，在大鼠和猴子的研究中，行为改善将至少持续8周。在完成对恒河猴的研究后，IND将提交给FDA。

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.