Point-of-care assay using Blood Glucose Meter for early warning of chronic lung rejection

Glucosentient, Inc., Champaign IL

Investigators

Linked publications, trials & patents

Abstract

Project Summary / Abstract Lung transplantation is the last treatment option for patients with end-stage lung diseases and to improve life expectancy and quality. While current technology has significantly improved the short-term survival rates, long- term survival remains a challenge due to chronic lung rejection, attributed to the development of Bronchiolitis Obliterans Syndrome (BOS), an irreversible and progressive decrease in lung function. Besides lung transplant, BOS is also a severe complication for patients receiving allogeneic hematopoietic cell transplant. Currently, diagnosis of BOS relies on the substantial and progressive reduction of lung function as measured by spirometry, but such a diagnosis would be too late for most treatments in order to slow down the deterioration of lung function. Recently, several biomarkers, including endothelin-1 (ET-1), sCD30, and KL-6, have been identified as predictive markers for BOS, making early warning possible. However, current methods for detecting these biomarkers are either cumbersome or expensive for point-of-care (POC) settings. To overcome these technological barriers in order to achieve the goal of providing early warning for BOS, we propose to develop a user-friendly device for POC monitoring for levels of ET-1, sCD30 and KL-6 based on the existing blood glucose meter (BGM) technology. By converting and amplifying the binding of non-glucose targets to their antibodies to release an enzyme called invertase, which catalyzes the conversion of sucrose to glucose, concentrations of these markers can be correlated to glucose, which can then be directly measured by a BGM. Specifically, based on the method developed for the ET-1 assay, we will first demonstrate the chemistry to obtain the critical invertase?sCD40 and ?KL6 conjugates, followed by assay development, optimizations, and last to integrate the optimized assays with an existing prototype cartridge system. Unlike current assays that rely on delicate instrument with highly trained operators, our proposed system is simple and inexpensive to be used at the POC settings. In addition, the biomarker tests will be utilize the same platform GlucoSentient has developed for tacrolimus, an immunosuppressant widely used by transplant patients and requires close monitoring. Today?s BGM is the culmination of decades of research and development, designed for convenient operation, low cost and large-scale production. Leveraging the BGM technology allows us to reduce the risks and costs associated with device development and scale up production. By combining the gold standard of antibody-based assays with the low cost and easy-to-use BGM technology, we aim to develop a single product that allows post- transplant patients and their doctors to monitor the risk of developing BOS and immunosuppressant levels. The proposed assays for BOS markers, alongside a recently developed assay to monitor tacrolimus, the most common immunosuppressant for lung transplant, has great potential to benefit both the physicians and patients to prevent chronic lung rejection and to improve long-term patient outcome.