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

脑癌是全球儿童和成人癌症死亡的主要原因。放射治疗(RT)作为儿童的一种治疗选择尤其有问题，因为它损害了正常的脑组织，并促进了神经功能障碍，导致记忆丧失和智力低下。RT的这些效应与正常分裂的神经前体细胞的损失有关，提供了在持续过程中维持和替换神经元所需的细胞。因此，当这一神经发生过程停止时，神经元会逐渐丧失，导致认知功能障碍。第一阶段显示，我们的新型再生肽TP508可以保护神经前体细胞免受RT的影响。此外，TP508似乎逆转了RT的作用，恢复了神经的完整性。因此，TP508似乎可以刺激神经发生，并可能成为预防RT诱导的认知功能丧失的一种新的候选药物。第二阶段将：1)确定TP508是否也保护癌症干细胞或其保护作用是否针对神经前体细胞；2)确定TP508是否减少RT诱导的神经元萎缩和认知损伤；以及3)确定TP508如何影响神经前体细胞和新神经元的生成。这些研究为临床开发TP508治疗RT引起的认知功能障碍和其他神经退行性疾病奠定了基础

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