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80万人患中风。由于缺乏治疗中风的疗法，开发胶质细胞生长因子2（GGF2）以促进中风恢复是重要的。GGF2也具有非常宽的治疗窗口（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，制造，配方和毒理学的障碍已经消除或大大减少。该申请的创新方面来自于利用已完成的GGF2的现有开发工作，用于另一种适应症，以有效地实现IND治疗卒中。在大量临床前数据的基础上，将在大鼠大脑中动脉闭塞（MCAO）中风模型中优化GGF2给药。研究将探索给药频率、延长给药持续时间并确定效应的持久性。将进行额外的毒理学研究，以实现针对卒中拟定的特定剂量方案。然后将在使用脑回恒河猴模型建立的皮质缺血的非人灵长类动物模型中确认GGF2功效。该模型强调神经恢复，而不是病变体积缩小。在大鼠和猴研究中，给药将在缺血后开始24小时开始，行为改善将随访至少8周。完成恒河猴研究后，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.