Preclinical Studies – Focused Ultrasound for DIPG

Diffuse intrinsic pontine glioma (DIPG) is a devastating glioma of the brainstem that affects the pediatric population.  Because of the sensitive location and diffuse nature of these tumors, surgical resection is not an option. In collaboration with the Hong Chen lab in the Department of Biomedical Engineering, the Rubin lab generates mouse models for DIPG in order to improve drug delivery to counter the progression of DIPG.  Two models are currently in use. Primary human xenograft cultures, a kind gift of Michelle Monje (Stanford University), are implanted into the brainstems of neonatal, immunocompromised mice. An engineered mouse model of DIPG, a kind gift of Orin Becher (Northwestern University), takes advantage of the RCAS system.  Chick fibroblasts expressing an avian retrovirus are implanted into the brainstem of neonatal mice that express an avian viral receptor under a nestin promoter. Retroviruses carry common transgenes overexpressed in DIPG, H3.3K27M and PDGFB, as well as Cre, which interacts with floxed p53 sites to delete p53 function.  These models are being used to test the efficacy of FUSIN, a technique which uses focused ultrasound-induced microbubble cavitation to enhance delivery of intranasally administered drugs to the brain (Ye et al, Journal of Controlled Release, September 2018).