Brain penetrating antibodies for treatment of neurodegenerative disease

The over-all aim of this project is to improve antibody therapy for Alzheimer’s (AD) and Parkinson’s disease (PD) by targeting neurotoxic protein aggregates with brain penetrating bispecific antibodies. Antibodies do not readily cross the blood-brain barrier (BBB).

To increase antibody concentration at the intrabrain target site, we have engineered therapeutic antibodies to be actively transported across the BBB by receptor mediated transcytosis (RMT).By a combination of advanced methods such as transmission electron microscopy, microdialysis, in vivo multiphoton microscopy, and PET imaging, we will visualize and quantitatively study three interdependent aspects of this concept in AD and PD mice:antibody transport across the BBB and into the brainantibody distribution in compartments of the brain – vasculature, interstitial fluid, and parenchymaantibody interactions with neurotoxic protein deposits of different solublilty, structure an locationsThis four year project will be led by the applicant and performed at Dept of Public Health/Caring Sciences, UU, with national and international collaborators from academia and industry, using imaging core facilities available at UU and SU.Antibody therapy is a promising strategy for disease modifying therapy in AD and PD, but many clinical trials have failed due to low drug concentrations in brain.

By advancing our understanding of a promising strategy for brain drug delivery, this study will help to advance CNS drug development.