Brain-Wide Quantification of Blood-Brain Barrier Penetrating Antibody Therapeutics

About This Grant

The process of delivering antibody-based therapeutics drugs to the brain is complicated by the need to penetrate the blood-brain barrier (BBB), prompting interest in BBB-penetrating strategies for antibody therapeutics. However, the methods to test brain penetration of these drugs are inadequate due to the intermingling of blood vessels and brain tissue, which confounds the signal of drug penetration. Current methods for measuring the distribution of antibody drugs in the brain are inadequate, lacking in accuracy, reliability and the capacity for three-dimensional, high-resolution, quantitative analysis. Addressing this technological shortfall, Translucence Biosystems is enhancing its proprietary 3D brain imaging and analysis platform to create a specialized Vasculature Subtraction Parenchymal Quantification (VSPQ) workflow. This tool aims to isolate and measure only the therapeutically relevant antibody drug within the brain parenchyma. The Phase II goal is to refine this approach to ensure precise measurement, leveraging the company’s experience and expertise in neuroscience, artificial intelligence (AI), and technology commercialization. The specific aims of the project are to develop and qualify the VSPQ workflow using machine learning algorithms to distinguish between vasculature and parenchyma signals, targeting 95% sensitivity and specificity relative to human assessments; integrate the VSPQ workflow into the existing 3D imaging platform, ensuring that the AI-generated data correlates strongly with manually partitioned regional data; validate the utility of the software through blind analysis of data provided by strategic partners, demonstrating its robustness and accuracy in real-world conditions; and validate a cloud- based version of the pipeline, ensuring that it is stable, reliable, and performs consistently with the local version. The impact of this research is poised to be significant, providing a vital tool for Alzheimer's disease drug discovery and potentially improving the rate of successful treatment development. By offering the VSPQ workflow as a cloud-based software-as-a-service, Translucence Biosystems is aiming to make this innovative technology widely accessible, thereby streamlining the drug development pipeline and bringing new therapies to patients more efficiently.