Cilia Biomarker Kit Development for Brain Injury Diagnosis and Prognosis.

Project Summary Traumatic brain injury (TBI) is a major clinical problem affecting more than 3 million Americans each year, and 60 million worldwide. Brain injuries are varied and depending on the region of the brain impacted, the cell type injured, or the gender of the person, outcomes can vastly differ. Misdiagnosing TBI can have devastating long-term consequences that can affect quality of life. Solutions are needed that can better accurately prognosticate outcomes post TBI. At present, substances in blood referred to as biomarkers serve as prognosticating tools for TBI outcomes. Two FDA-approved biomarkers namely GFAP and UCH-L1 are used to triage mild TBI (mTBI) patients that don’t need unnecessary computer tomography scans. Both GFAP and UCH-L1 proteins are released from cells upon injury and are found in neurons and glial cells. CIAN, Inc. has preliminary data that suggests that blood flow and blood vessel health are important components of TBI progression, and the endothelial cells that underlies the blood vessel needs to be accounted for in biomarkers. A hair-like organelle called cilium that senses blood flow gets dismantled upon high or disturbed blood flow conditions, which were observed in mTBI and severe TBI. Our hypothesis is that vascular blood flow-associated markers in cilium when combined with neuronal and glia markers will provide better outcome determination post TBI. CIAN, Inc, technological innovation is based on the ciliary proteins expressed in the cilium that serve as surrogate markers of vascular flow changes in TBI in blood. The long-term goal of this project is to develop a point-of-care test that is based on ciliary biomarker detection in a drop of blood. To facilitate this long-term objective, we need to develop specific monoclonal antibodies and an immunoassay that can be miniaturized. In this STTR phase I project, CIAN, Inc. will develop antibodies towards two protein targets that are expressed in cilia (aim 1), and an immunoassay (aim 2) to detect these proteins in human plasma. Combining the two objectives will result in a kit that can be run on colorimetric based ELISA readers available in most clinical labs in levels 1 and 2 trauma centers in the US. In Phase II, we will validate the assay on TBI samples to facilitate the development of a CLIA lab test. The commercial opportunity here is to have a TBI prognosticating or monitoring biomarker test available in 450 level 1 or 2 trauma centers in the US.