(SST) James T. Rutka Pediatric Brain Tumor Award (2023 Award winner):treatment of Intracranial DIPG with Oncomagnetic Therapy: Potentiation with Ketone Bodies
Vice Chairman and Residency Program Director, Director, Kenneth R. Peak Brain and Pituitary Tumor Treatment Center Houston Methodist Hospital Houston, Texas, United States
Disclosure(s):
David S. Baskin, MD, FACS, FAANS: No financial relationships to disclose
Introduction: DIPG is an inevitable fatal childhood brain cancer with 5-year survival of < 1%. DIPG is biologically distinct from other adult high-grade gliomas. Responses to chemoradiotherapy are poor. We have developed Oncomagnetic therapy by exploiting a known quantum phenomenon which can differentially target cancer cell mitochondrial flux, externally applied spinning oscillating magnetic fields (sOMF). We have also demonstrated that sOMF has profound deleterious effects on cancer cells in vitro, in vivo and patients. Ketone bodies like β-hydroxybutyrate (βHB) are preferentially used by brain cells as fuel. We postulated that βHB metabolism by DIPG should potentate the action of sOMF, as the hyperpolarization of mitochondria should increase the steady state levels of biradical pairs in respiratory transport complexes, and would be a result of increased mitochondrial ROS generation.
Methods: In vitro studies growth inhibition and clonogenic studies were performed using standard DIPG cell lines. Oxygraph studies were performed to measure cellular mitochondrial function over five days. Optical probes MitoTracker, MitoSox, and H2DCF were used to measure mitochondrial membrane potential and ROS production. An intracranial mouse DIPG model was used to examine sOMF on DIPG lethality.
Results: In vitro studies show that sOMF kills DIPG and sOMF treatment increases life expectancy in the DIPG mouse model. βHB strongly potentiates sOMF, decreasing cell viability and increasing apoptotic cell death in DIPG cells. βHB supplementation of sOMF significantly reduced mitochondrial oxygen consumption in DIPG cells compared to controls. Significant dose-dependent increases in mitochondrial activity and ROS production were observed. Combining sOMF and βHB greatly inhibited DIPG clonogenicity.
Conclusion : We demonstrate that sOMF can be used to kill DIPG cells in vitro and to increase animal survival in vivo. sOMF therapy is a highly promising approach to treating this fatal childhood disease. Our in vitro studies indicate that coupling sOMF to ketone therapy could aid DIPG patient survival.
