Background
The blood-brain barrier (BBB) is a selective semipermeable membrane that separates the circulating blood from the brain parenchyma where the neurons and glial cells that are the targets of therapeutics reside. One of the major challenges in developing effective treatments for neurological disorders is engineering therapeutic agents to cross the BBB and reach their targets within the central nervous system (CNS). Consequently, the development of human based antibody shuttles has become an area of active research for CNS therapeutic delivery.
With the recent approval of three antibody therapeutics for Alzheimer's Disease, a large effort is underway to generate next-generation antibodies that harness 'brain shuttle' mechanisms to cross the BBB in the brain parenchyma.
How We Study Human-Based Antibody Therapeutics and the Blood Brain Barrier
Leveraging 3D tissue clearing, light sheet imaging, and AI-powered quantification, Translucence Biosystems provides comprehensive data informing the development of human-based antibody shuttles for CNS therapeutic delivery across the BBB.
Recent collaborative work with Lundbeck has shown that by binding an antibody against BACE1—an enzyme involved in the production of β-amyloid in Alzheimer’s disease pathology—to a transferrin receptor (TfR1) found in blood vessel endothelial cells, therapeutics can be shuttled across the blood-brain barrier (BBB). This shuttling is enabled by the TfR1 receptor, which usually shuttles iron across the BBB. Translucence Biosystems recently presented some of our latest findings at the Alzheimer's Association International Conference® (AAIC24), visit our newsroom for more information.
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Human Based Antibody Therapeutic Imaging and Identification
Translucence Biosystems employs our modified iDISCO+ protocol to render intact brain samples optically transparent and performs whole-brain immunostaining to label vasculature, as well as the therapeutic agents or compounds of interest. Whole-brain immunostaining, enabled by an anti-human Secondary antibody, allows for the visualization of the distribution and potential penetration of therapeutic agents across the blood brain barrier. These 3D visualizations surpass other imaging methods used to monitor therapeutics in the brain by providing an unbiased and complete view of the entire brain
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Brain-wide Quantification of Human Based Antibody Therapeutics
Translucence Biosystems' AI-powered Voxels software aligns samples to a common reference atlas to quantify the distribution of therapeutic agents or compounds within various brain regions. This quantitative analysis provides valuable insights into the extent of blood-brain barrier penetration and the spatial distribution of the compounds of interest, which can inform the development of more effective drug delivery strategies.
Summary
By leveraging light sheet imaging, tissue clearing, and AI-powered quantification pipelines, Translucence Biosystems is able to study human-based antibody therapeutics and the blood brain barrier. These techniques allow us to evaluate the delivery of novel therapeutics, contributing to the development of more effective treatments for neurological disorders.
