Receptor agonist reverses and prevents memory loss in Alzheimer's disease

When researchers stimulated endothelin B receptors in rats with Alzheimer’s disease (AD), the rats showed improved memory, reduced oxidative stress, and enhanced neurovascular remodeling, according to a new study presented September 4, 2015 at the 14th International Conference on Endothelin: Physiology, Pathophysiology and Therapeutics in Savannah, GA.

Previous studies have found that endothelin B receptors are important for brain development and neuroprotection. The purpose of this study was to test the effects of IRL-1620, an endothelin B agonist.

“We used the novel approach of stimulating the endothelin B receptors by intravenous injection of IRL-1620 to prevent and repair the damage to the brain caused by Alzheimer’s disease,” said study co-author Seema Briyal, PhD, research associate in neuropharmacology at Midwestern University’s Chicago College of Pharmacy in Downers Grove, IL.

In this study, the researchers first gave the rats amyloid beta to develop Alzheimer’s disease. These rats showed impaired learning and memory, and increased oxidative stress. The researchers then injected the rats with IRL-1620.

“We found that treatment with IRL-1620 reversed these effects. Intravenous injection with the drug improved memory deficit by 50% to 60% and reduced oxidative stress by 45% to 50%,” Dr. Briyal said. “We also found that treatment with IRL-1620 enhanced certain recovery processes within the AD-damaged brain, resulting in more new blood vessels and neuronal cells. This indicates reparative processes occurring in the damaged brain.”

Currently, the FDA has approved 5 medications to treat Alzheimer’s disease. However, these drugs only help to mask the symptoms; they don’t stop the disease from progressing or treat the underlying disease.

This is the first report to demonstrate that using IRL-1620 to selectively stimulate endothelin B receptors improves memory, reduces oxidative stress, and enhances neurovascular remodeling in an animal model of Alzheimer’s disease, according to Dr. Briyal and co-author Anil Gulati, MD, PhD, Associate Dean for Research and Professor at Midwestern University’s Chicago College of Pharmacy.