“Our goal with this new class of agents is to see if we can, first of all, augment then cholinesterase inhibitors for symptomatic treatment, and secondly, maybe even act alone as an independent agent early in the disease process.”

Paul Newhouse, MD, is working with a group of researchers on the putative cognitive enhancer VU319, a muscarinic M1-positive allosteric modulator being tested for Alzheimer Disease in a phase I trial (NCT03220295).

None of the previous muscarinic agonists from the 1990s and early 2000s worked as well as those in the field would have hoped, as non-selective binding mechanisms caused unforeseen issues and unwanted adverse effects.

The director of the Vanderbilt Center for Cognitive Medicine and the Jim Turner Chair in Cognitive Disorders at the Vanderbilt University School of Medicine spoke with NeurologyLive about the trials and tribulations of the previous muscarinic agonists, and how their failures have better informed the development of this investigational agent, VU319.