RISE Talks Series

Who? Jean E. Lachowicz, Ph.D., Principal, Five Points Pharma Consulting What? Modifying Drugs and Biologics to Improve CNS Distribution When? 12:00-1:00 on Thursday, October 29 Where? Hall of Sciences, Room 326

Achieving adequate brain exposure has been a constant challenge in development of drugs and biologics for CNS disorders. The blood-brain barrier, which is made up of endothelial cells with tight junctions and efflux proteins, severely limits the brain permeability of therapeutic agents. While efficient at blocking xenobiotics from entering the brain, the BBB is also adept at transporting necessary glucose, amino acids, ions and proteins from the circulation to the brain. One such mechanism is receptor-mediated transcytosis and includes insulin, LRP1 (Low density lipoprotein receptor-related protein I), and transferrin receptors. Conjugating drugs or biologics with peptides or antibodies that are recognized by these receptors has been shown to facilitate transport across the blood-brain barrier, resulting in therapeutic exposure levels. Examples of therapeutics that have been successfully modified to utilize receptor-mediated transcytosis include anti-Abeta mAbs for treatment of Alzheimer’s Disease, replacement enzymes for inherited disorders of metabolism, and taxanes for brain tumors.