A Novel Drug Delivery Method for the Treatment of Diffuse Intrinsic Pontine Glioma

Background

Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood cancer with very poor prognosis. Currently, no cure or effective treatment is available. One of the main problems with treating such an invasive tumor involves poor drug delivery to the brain, as most therapeutics cannot cross the tightly regulated blood-brain barrier.

Project Goal

The first part of this project will use convection-enhanced delivery (CED) to effectively deliver a drug of choice (dasatinib) into the brain of mice and assess its volume of distribution. This technique involves direct injection of the therapeutic into the cranial cavity. Moreover, the effectiveness of this technique will be intra-operatively monitored by chemically double-labeling dasatinib (without altering its activity) with a PET imaging probe and with a fluorophore that will permit drug localization post mortem. We believe that the route of administration chosen and the modifications applied to dasatinib will improve drug delivery to the brain. 

Once the efficacy and the volume of distribution of dasatinib CED have been determined, the second part of this project will focus on assessing whether the double-labeled molecule is efficacious in reducing DIPG morbidity and mortality. For this purpose, mice will be injected with human-derived DIPG cells to develop the tumor themselves. Following this procedure, double-labeled dasatinib will again be delivered through CED with intra-operative imaging. Tumor regression will be assessed with imaging in vivo. Tumor markers and downstream effectors of dasatinib will be histologically analyzed post mortem.

Overall, this study will provide a new therapeutic model for the treatment of DIPG.