MQSNA - Occluding brain arteriovenous malformations using molecular targeting

We have completed our studies of endothelial molecular changes after radiation and chosen 6 targets that are prospective for vascular targeting treatment. In addition, our recent in vivo work has shown that the technology can achieve occlusion of large vessels (> 2mm diameter), thus overcoming one of the major concerns regarding potential clinical translation.

In the current project, we are investigating nanotechnology to improve the delivery system for vascular targeting. By using nanodiscs, we propose that a larger payload of the thrombotic molecules can be delivered, and that stable adherence to the target molecule can be improved.

With Safety net funding, we will continue our investigation of nanodisc delivery systems targeting endothelial surface phosphatidylserine and PDCE2, our most prospective targets. We will do this in the in vitro testing system, which uses pulsatile circulating whole blood in a closed circuit and endothelial cell culture. We will use primary endothelial cell cultures from surgical AVM specimens as well as endothelial cell lines. It is the consumables for this work that will be funded by the Safety net grant.

With the in vivo results showing complete occlusion of large vessels, and results from the nanotechnology testing, we believe an application for NHMRC funding will have a greater chance of success in 2018.

Budget
Cell culture consumables: $9,000
Nanodiscs: $5,000
Antibodies: $3,000
Conjugation kits: $3,000
TOTAL: $20,000