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
