MEDU-36. MERIVA® AND A NOVEL CHEMICALLY-MODIFIED CURCUMIN FOR THE TREATMENT OF MEDULLOBLASTOMA

Medulloblastoma is the most common pediatric central nervous system cancer, and despite an overall favorable prognosis with intensive multimodal treatment, children are especially at risk for significant negative effects of these treatments. There is a need for treatments that are less toxic with fewer negative long-term sequelae. Curcumin, the active component of the dietary spice turmeric, has shown promising anti-cancer effects in vitro and in preclinical models of many types of cancer, including medulloblastoma. Along with its potent anti-cancer effects, low toxicity and a wide therapeutic window make curcumin an ideal candidate as a novel therapeutic for pediatric cancer. A major barrier to achieving curcumin’s potential is poor bioavailability. To address this challenge we are focusing on two approaches: Meriva and TRB-N0224. Meriva is a curcumin-phosphatidylcholine complex shown to have 18-fold higher absorption than unformulated curcumin, while TRB-N0224 is a chemically modified curcumin. Our objective is to demonstrate therapeutic efficacy in an animal model of medulloblastoma. In vitro studies were conducted using the primary cell lines IMB226 sonic hedgehog-type cells (SHH) and D425MED group 3 medulloblastoma cells. Animal studies were performed using 2 models: a D425MED orthotopic xenograft model in immunocompromised mice and an orthotopic transplant model of group 3 medulloblastoma (Myc + DN-p53) in syngeneic C57BL/6 mice. We have demonstrated in vitro efficacy of both Meriva and TRB-N0224 against SHH and group 3 medulloblastoma cells. The D425MED animal model revealed negligible efficacy of Meriva using either oral or intraperitoneal administration. A pilot study with the Myc + DN-p53 model revealed a dose-dependent trend toward therapeutic efficacy of both Meriva and TRB-N0224 which point to a possible immunomodulatory role of curcumin in the control of tumor growth. Experiments with larger cohorts are in progress.