Cognitive dysfunctions are common symptoms for Alzheimer's disease, schizophrenia, and other disorders of the central nervous system. Most people are familiar with the memory problems as one type of dysfunction, but cognitive dysfunctions encompass other aspects such as language use, complex attention, and social cognition. Researchers at the Warren Center for Neuroscience Drug Discovery at Vanderbilt University School of Medicine Basic Sciences have been at the forefront of drug discovery efforts to treat serious brain disorders.
VU319, a compound designed to improve memory loss in people with Alzheimer's disease, advanced into phase 1 clinical trials in 2020. The results were promising: VU319 demonstrated cognitive improvements with no side effects. To expand upon their previous work, researchers led by Craig Lindsley, University Distinguished Professor of Biochemistry and Pharmacology and executive director of the WCNDD, aimed to develop a backup compound for VU319 that might show additional therapeutic potential.
Their work was published in ACS Chemical Neuroscience in August 2024. The backup candidate compound, VU6007496, is a positive allosteric modulator—a PAM—for a neurotransmitter receptor called M 1 muscarinic acetylcholine receptors. PAMs selectively bind to a particular part of a receptor in a way that they can modulate the receptor's activity.
Neurons that produce the neurotransmitter acetylcholine fail in the beginning stages of Alzheimer's disease, but usin.