GLUCOSENTIENT INC — Department of Health and Human Services STTR Phase I: 102

Description

Project Summary Abstract The objective of this Phase I STTR project is to demonstrate feasibility of developing a selective affordable and pocket sized device to enable regular and quantitative monitoring of both Li and Na levels in the blood of patients with bipolar disorder BD which is one of the most common mental illnesses affecting over million Americans costing the healthcare system over $ billion dollars annually Even though lithium Li therapy is one of the most effective and affordable long term treatments for BD andlt of BD patients are prescribed with Li in large part because of its very narrow therapeutic window mM between ineffectiveness or very severe side effects Managing the inherent risk and maximizing the benefit of Li therapy requires convenient and regular monitoring of Li and Na whose level can fluctuate during Li therapy a technological niche that remains unfilled because of current POC devices are either too expensive bulky or vulnerable to interferences from other metal ions or species in blood To achieve the objective we will employ a combinatorial method called in vitro selection to obtain DNA molecules with enzymatic activity DNAzymes that are highly specific for either Li or Na from a large library of up to differences and will include negative selection to remove the populations that interact with known or anticipated interfering ions or species In addition we will repurpose the low cost and pocket sized blood glucose meter BGM into a more general meter for monitoring Li and Na levels The innovation lies in converting the selective Li or Na dependent cleavage by DNAzymes to effective release of an enzyme called invertase that can catalyze conversion of sucrose into glucose which can then be quantified using the BGM By combining DNAzymes with the BGM platform we can mitigate the risk associated with developing and manufacturing medical devices while ensuring the end product will be low cost convenient user friendly and amenable for scale up production Specifically we propose to employ in vitro selection to obtain and optimize Li or Na specific DNAzymes with high activity for cleavage We will develop solution assays for Li and Na relaying the selective recognition catalysis of DNAzymes to a BGM detectable glucose signal using invertase a protein that hydrolyses sucrose into glucose for both signal transduction and amplification The assay will be validated in clinical samples Finally we will develop disposable cartridges for BGM based POC monitoring of Li and Na The expected outcomes for this Phase I project are BGM based Li and Na assays with analytical performance validated in clinical samples and demonstrating the feasibility of performing the developed assays in a prototype cartridge system The product can be readily adapted to other biomarkers that will be relevant in assessing the states and needs of the patient Project narrative Although lithium therapy is one of the most effective and affordable long term treatments for bipolar disorder BD less than of BD patients are prescribed with lithium drug in large part because of its very narrow therapeutic window mM between ineffectiveness or very severe side effects By adapting widely available blood glucose meter and highly selective DNAzymes to detect lithium and sodium whose level is related to lithium level in the blood this STTR Phase I project will demonstrate feasibility of developing a novel affordable and pocket sized device to enable regular and quantitative monitoring of both Li and Na in the blood of BD patients Accomplishing the goal will improve effective and wider use of Li therapy in BD patients by enabling more precise control of Li dosing which will have a major impact in improving the lives of the patients with this common disorder and lowering their healthcare costs