A fast-acting compound that appears to improve cognitive function impairments in mice similar to those found in patients with progressive Alzheimer's disease has been identified by scientists at Wake Forest University School of Medicine and the Vanderbilt University Medical Center Program in Drug Discovery. Researchers hope to one day replicate the result in humans.
The compound - benzylquinolone carboxylic acid (BQCA) - has also been shown in previous rodent studies to lessen the occurrence and severity of the behavioral disturbances often symptomatic of Alzheimer's, such as hallucinations, delusions, paranoia and outbursts.
"That makes this compound somewhat novel," said Michelle M. Nicolle, Ph.D., an associate professor of gerontology at Wake Forest and co-researcher on the study, published recently in the Journal of Neuroscience. "We wanted to see if this very specific acting compound was able to change the way the brain works and whether or not it improved memory in our 'Alzheimer's mice,' which are experiencing progressive cognitive decline much like a person with Alzheimer's does."
Other attempts to identify such a specific treatment for Alzheimer's have failed, according to Nicolle.
"Current treatments only treat the symptoms while the underlying disease is still progressing," she said, "so recent research efforts are focusing on stopping disease progression instead of symptomatic treatment."
The researchers' findings suggest that the compound could alter the progression of disease in mice and, ultimately, hold importance for humans, as well.
BQCA activates a specific neurotransmitter receptor in the brain called the M1 muscarinic acetylcholine receptor. M1 receptors have been the focus of research into treatment of Alzheimer's disease because they affect the part of the brain that stimulates the memory and learning functions the disease inhibits. Until now, scientists have not found a treatment selective enough to activate the receptors without producing side effects such as nausea, vomiting and increased frequency of urination.
But in this study, Nicolle said, researchers found that BQCA boosted the weak signals of the M1 receptors in a mouse model of Alzheimer's disease.
"In Alzheimer's disease, the chemical signals - the little bits of information that are talking to each other in the brain - are reduced, so you can't do the tasks very well," Nicolle said. "BQCA is only boosting an existing signal, so it's really specific in its action."
BQCA also seemed to inhibit production of amyloid beta, one of the markers of Alzheimer's disease in the brain - perhaps key to the compound's potential for slowing the progression of the disease.