This technology combines stem cells, heat-inducible gene expression and ultrasound to remotely permeabilize the blood brain barrier, enabling targeted delivery of therapeutics to the brain.
A major challenge in treating brain disorders such as neurodegenerative diseases or glioblastoma is the presence of the blood brain barrier (BBB), which prevents the entry of potentially toxic compounds into the brain. Current strategies to permeate the BBB include osmotic agents that shrink brain endothelial cells, physical disruption with high-intensity focused ultrasound (HIFU), increasing the lipophilicity of drugs, and packaging drugs into vectors that cross via receptor-mediated endocytosis. However, these methods have toxic side effects, cannot be completely controlled, or produce inconsistent results. There is a need for improved therapeutics or vector designs capable of permeating the BBB with fewer side effects, in order to improve treatment options for brain-related diseases.
This technology places genes encoding therapeutic or cytokines, such as TNF-alpha, under the control of Heat Shock Proteins (HSP) promoters for selective delivery of therapeutics to the brain. The plasmids containing inducible genes can be directly targeted to tumors or can be engineered into cell delivery vehicles, such as tumor homing stem cells, which can then be injected systemically or directly into the brain. Expression of the genes can be remotely controlled in response to cellular stresses, including standard-of-care chemotherapeutic agents such as temozolomide. Additionally, this technology can be used to control BBB permeability for a variety of therapeutic applications. Therefore, this technology may improve delivery of therapeutics across the BBB to treat brain tumors, neurodegenerative disease, and inflammation.
This technology has been validated with stem cell lines and in studies where stem cells were implanted into the brains of mice treated with temozolomide, which induced expression of encoded proteins.
Patent Pending
IR CU19217
Licensing Contact: Jerry Kokoshka pli