IGF::OT::IGF TP508 MITIGATES RADIOTHERAPY-INDUCED TISSUE DAMAGE - PERIOD OF PERF

脑癌是全世界儿童和成人癌症死亡的主要原因。放射治疗（RT）作为儿童的治疗选择尤其有问题，因为它会损害正常的脑组织，并促进神经功能障碍，导致记忆丧失和智力迟钝。RT的这些作用与神经祖细胞的损失有关，神经祖细胞通常分裂，提供在持续过程中维持和替换神经元所需的细胞。因此，当这种神经原性过程停止时，神经元逐渐丧失，导致认知功能障碍。第一阶段表明，我们的新的再生肽，TP 508，保护神经祖细胞从RT的影响。此外，TP 508似乎逆转RT恢复神经完整性的影响。因此，TP 508似乎刺激神经发生，并可能是一种新的候选药物，以防止RT诱导的认知功能丧失。第二阶段将：1）确定TP 508是否也保护癌症干细胞或其保护作用是否特异于神经祖细胞; 2）确定TP 508是否减少RT诱导的神经元萎缩和认知障碍;和3）确定TP 508如何影响神经祖细胞和新神经元的产生。这些研究为TP 508治疗RT诱导的认知功能障碍和其他神经退行性疾病的临床开发奠定了基础

Brain cancer is a leading cause of cancer mortality in children and adults worldwide. Radiation therapy (RT) is especially problematic as a treatment option in children because it damages normal brain tissue, and promotes neurological dysfunction leading to memory loss and mental retardation. These effects of RT are associated with loss of neuroprogenitor cells that normally divide providing cells required to maintain and replace neurons in a continuing process. Thus, when this neurogenic process is stopped, there is gradual loss of neurons leading to cognitive dysfunction. Phase I showed that our novel regenerative peptide, TP508, protects neuroprogenitor cells from effects of RT. In addition, TP508 appears to reverses effects of RT to restore neural integrity. TP508 therefore appears to stimulate neurogenesis and may be a novel drug candidate to prevent RT-induced loss of cognitive function. Phase 2 will: 1) determine whether TP508 also protects cancer stem cells or whether its protective effects are specific for neuroprogenitor cells; 2) determine whether TP508 reduces RT-induced neuronal atrophy and cognitive impairment; and 3) determine how TP508 affects neuroprogenitor cells and generation of new neurons. These studies lay the groundwork for clinical development of TP508 for treating RT-induced cognitive dysfunction and other neurodegenerative disease