A Blood-Brain Barrier (BBB) Shuttle-Assisted Insulin Receptor Antibody for Neuroprotection in TBI
Examining the potential neuroprotective applications of monoclonal antibodies (mAbs) in traumatic brain injury.
Project at a Glance
Product Type:
Therapeutic
Project Start Date:
7/1/2021
Principal Investigators: Colin Greineder, MD, PhD
Peter Tessier, PhD
Solution Sheet:
Download Solution Sheet (PDF)
Funding History:
$123,717 in non-dilutive funding • 2021 $98,717 Massey Grand Challenge
• 2021 $25,000 Bioinformatics Institute • Substantial departmental, school and center based support
Overview
The strategy for delivering mAbs into the central nervous system (CNS) is called the “BBB shuttle” and involves engagement of a surface target on the luminal membrane of cerebrovascular endothelial cells.
Insulin receptors are highly expressed on the surface of neurons and are widely distributed throughout the brain. Insulin signaling activates key survival pathways in neurons, leading to its investigation in chronic neurodegenerative disease (e.g., Alzheimer’s) and acute brain injury. CNS delivery of insulin via high-dose intranasal administration has been shown to reduce brain lesion volume and improve functional outcome after TBI in rats.
Significant Need
Despite more than 30 phase III prospective clinical trials, no neuroprotective agents have been found to improve clinical outcomes in patients with TBI, and the standard of care for this devastating condition remains largely supportive. One of the primary challenges in therapeutic development for TBI and other brain injuries has been the need for penetration across the blood-brain barrier (BBB).
Monoclonal antibodies (mAbs), with their extreme specificity, well-defined plasma pharmacokinetics (PK), and potential for molecular imaging to define tissue concentrations, offer the potential to intervene on specific mechanisms with well- defined dosing and duration of target engagement.
While these characteristics have helped make mAbs the fastest growing drug class in terms of both new clinical trials and approvals, they have been largely excluded from TBI research due to their inability to cross the BBB.
Competitive Advantage
The pharmaceutical profile of therapeutic antibodies suggests that BBB-shuttled mAbs will have straightforward formulation and a shelf life on the order of several weeks, making administration by paramedics and/or combat medics feasible.
Funding Organization(s)
Publications
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