Central nervous system (CNS) diseases including neurological, oncological and psychiatric conditions, are the biggest healthcare expense worldwide. Biotechnological drugs such as antibodies have shown therapeutic progress elsewhere in the body, but the blood brain barrier (BBB) limits their usefulness in CNS diseases. The benefit of macromolecules mostly comes from higher specificity and safety over traditional small molecule approaches and macromolecules such as antibodies can be more easily tagged and imaged than small molecules. We have demonstrated the feasibility of merging technologies of antibody radiolabeling and intra-arterial delivery and observed impressive benefits of this route of delivery to the brain. Will plan to perform mechanistic studies to better understand the process of antibody extravasation, which will provide key insights for widespread implementation of this technique to the clinical setting.

The Warfighter Brain Health (WBH) Initiative is a joint effort between the operational and medical communities. The WBH Initiative: Strategy and Action Plan outlines the Department of Defense’s direction to better address the brain health needs of our Service members, their families, line leaders, commanders, and their communities at large. The strategy and action plan addresses brain exposures, to include blast exposures, traumatic brain injury (TBl) and long term or late effects of TBl, with the goal of optimizing brain health and countering TBI

Ischemic stroke is the most frequent cause of long-term severe disability and places an enormous economic burden on society. A critical aspect in guiding treatment decisions is determining the penumbra, i.e., the region of injured brain tissue around the ischemic core that can potentially be revived. The overarching goal of this proposal is investigating the use of hyperpolarized 13C metabolic imaging in a novel endovascular pig stroke model as a new tool for improved detection of stroke penumbra that can be translated into the clinic.

The sanctuary site of the central nervous system shields it from the benefits of correcting mutations by CRISPR-based genome editing. We plan to use artificial intelligence for the in silico design of critical molecules, which are expected to overcome this limitation. While we propose to test our novel approach in unequivocally lethal amyotrophic lateral sclerosis, our expectation is that our approach can be duplicated to correct other mutations in the brain.

The primary goal of the project is to develop a novel method of radiolabeling T cells based on radiocarriers, and not small molecules, to follow the biodistribution of T cells and their penetration to organs and solid cancers.