Description:
The proposed invention involves identification and characterization of molecular targets for treating intracranial aneurysms. A focus is endothelial podosomes regulated by the transmembrane receptor protein THSD1. THSD1 also regulates autophagy processes that contribute to aneurysm formation as well as positively regulates TGFβ signaling, which may ameliorate IA disease.
Technology Overview
The technology is a novel therapeutic approach to treat intracranial aneurysms via elucidation and characterization of several genes involved in endothelial podosome formation, which has been shown to regulate matrix integrity in the vascular tissues, and autophagy processes, which destabilize the cell-matrix interactions. A lead candidate is the gene encoding THSD1, mutations in which have been linked to the pathogenesis of intracranial aneurysm.
Components
Immortalized cell lines and mouse models expressing missense mutations in THSD1 are described with this technology as platforms to test novel therapeutic compounds targeting autophagy and endothelial podosome formation. Also, a procedure to identify and characterize novel THSD1 variants in human samples from patients who have suffered from intracranial aneurysm.
Benefits/Technology Advantages
THSD1 controls a number of different cellular processes that can play a role in amelioration of disease pathogenesis associated with intracranial aneurysm. The proposed therapeutic approach could be the first of its kind to modulate endothelial podosome formation and reduce abnormal dilation of cerebral artery walls to prevent rupture.
Potential Applications
Intracranial aneurysm is a cerebrovascular disease that predominantly occurs in the cerebral artery and leads to subarachnoid hemorrhage (SAH), a rupture of the cerebral artery that is a major cause of stroke. SAH accounts for >25% of years lost for all stroke victims under the age of 65 years. The SAH mortality rate is 40% and only half of survivors return to independent life. This technology could elucidate novel therapeutic approaches to improve clinical outcomes associated with intracranial aneurysm through early therapeutic intervention. It could eventually lead to a pharmacological or gene-based therapy that could be delivered to patients following an aneurysm within the intensive care setting to reduce the risk of subsequent SAH.
Intellectual Property Status
Patents pending, U.S. Application No: 17/824,612; 17/824,621; 17/824,631; and 17/824,641
Portfolio available for licensing.
Stage of Development
Concept
About the Creator/Inventor
Dong H Kim MD
Professor of Neurosurgery