Chemical Engineering pres.
ChE Seminar Series: Eric Shusta
University of Wisconsin – Madison
Antibody Engineering Strategies to Overcome the Blood-brain barrier
Millions of people worldwide are afflicted with neurological diseases such as Parkinson's disease, Alzheimer's disease, brain cancer, and cerebral AIDS. Although many new drugs are being developed to combat these and other brain diseases, few new treatments have made it to the clinic. The impermeable nature of the brain vasculature, also known as the blood-brain barrier (BBB), is at least partially responsible for the paucity of new brain therapeutics. As examples, approximately 98% of small molecule pharmaceuticals do not enter the brain after intravenous administration, and the BBB prevents nearly all protein and gene medicines from entering the brain. Our research group is therefore focused on developing tools for the analysis of the brain drug delivery process and identifying novel strategies for circumventing this transport barrier. This presentation will detail our recent work focused on overcoming BBB restrictions on brain drug delivery. To this end, we are mining large antibody libraries to identify antibodies that can target and act as artificial substrates for endogenous receptor-mediated BBB nutrient transport systems and ferry drug cargo into the brain. In addition, the BBB can be disrupted in certain disease conditions such as brain tumors. For these applications, we are identifying antibodies capable of targeting brain extracellular matrix to leverage this pathological BBB disruption for drug accumulation. After conjugation to drug payloads that can include small molecules or biologics, we have demonstrated that both classes of antibodies have the potential to deliver medicines to the brain.
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