Abbie Wells, & Dr. William Munroe
Senescent cells, cells that are associated with tissue damage, cellular damage, and cancer, are linked with inflammation, tissue destruction, and various other conditions in the human body. These cells are linked with the natural aging process, therefore increasing geriatric quality of humans. To treat this, senolytic drugs, such as ARV-825, have been produced. ARV-825 is a novel senolytic bromodomain protein family (BET) inhibitor that uses proteolysis-targeting chimera technology (PROTAC). This means that ARV-825 has been engineered to cause protein degradation and apoptosis. Specifically, ARV-825 prompts apoptosis while reducing the expression of BRD4, a senescent cell marker. This specific drug aims to treat “side effect” cells that are the result of Neuroblastoma, a very common solid childhood tumor. Due to its potency and its ability to cause protein degradation and apoptosis, ARV-825 is efficient in treating senescent cells that are a response to tumor secretions, body inflammation, and gene-impacting treatments such as chemotherapy. Planaria, specifically the Girardi sp., is a freshwater flatworm we are utilizing as a model system to test the effectiveness of ARV-825. These worms have pluripotent stem cell promoters that aid in rapid tissue regeneration. To examine this, planaria viability was tested at different ARV-825 concentrations, resulting in a 25% survival rate in 1µM concentrations, and a 50% survival rate at concentrations 2µM-10µM. Quick tissue regeneration rates coupled with the fact that planarians share morphology and tissue function with many other animals make this species valuable to scientific research. By testing this ARV-825 in a planaria model system, as opposed to a human or mouse model, the drug’s mechanism can be tested and compared to see if these mechanisms are conserved among different organisms. This data may be used to further research the implications of ARV-825 and its efficiency in treating senolytic cells.