Stephen Brimijoin, Ph.D.

We are broadly interested in the molecular neurobiology, pharmacology, and toxicology of cholinesterases, including the role of these enzymes in neurotransmission and their involvement in disease. Early on we produced monoclonal antibodies that unexpectedly destroyed cholinergic pathways in rats, which led to a unique animal model for neuro-immunology. Later we studied cholinesterases as biological targets of drugs, chemical warfare agents, and pesticides, and also as active participants in neurological disorders.

We showed acetylcholinesterase can promote deposits of brain amyloid in Alzheimer's disease and, with other Mayo investigators, we worked to design new drugs to block this pathologic effect, creating a novel line of transgenic mice to test their therapeutic potential. Our current focus is developing modified cholinesterase molecules as agents for treatment of drug abuse. We helped re-engineer human plasma cholinesterase into a form that hydrolyzes cocaine fast enough to rescue rats from lethal overdose and prevent them from seeking cocaine as a reward.

Now using animal models, we are mounting an intense effort to determine whether viral gene transfer of these enzymes can suppress psychological and behavioral responses to cocaine for an indefinitely long period of time.

Our number one goal is to lay the scientific basis for a clinically effective treatment that helps former users avoid the risk of relapse into drug addiction.This work