Science: New Combination Drug Therapy for Alzheimer’s

A “cocktail” of inhibiting drugs may prove to be a successful treatment for Alzheimer’s disease, according to a new study on mice published in Science Translational Medicine. reports. This combination therapy, which targets two specific enzymes simultaneously, is thought to be safer and more effective than current treatments using drugs that target only one of these enzymes.

“Our study provides validation for this type of combination drug therapy that can be developed in the future for the treatment of Alzheimer’s disease,” said Philip Wong, co-author and neuroscience professor at Johns Hopkins University.

Alzheimer’s is a progressive and fatal brain disease that affects an estimated 30 million people worldwide. The disease destroys brain cells, causing memory loss and serious mental and behavioral problems. With no cure, Alzheimer’s is currently the seventh-leading cause of death in the United States.

The leading theory explaining the cause of Alzheimer’s is thought to be the accumulation of the toxic protein amyloid-beta, coined amyloid plaque. Previous studies have shown that production of amyloid plaque is prevented or reduced in brains of mice when either of two enzymes, beta-secretase or gamma-secretase is inhibited. Yet, it has been found that overly inhibiting these enzymes produces dangerous side effects.

For example, inhibiting beta-secretase too much impairs nerve function, and causes schizophrenia-like symptoms in mice. Likewise, inhibiting gamma-secretase too much leads to a variety of abnormalities, including developmental defects, skin tumors and a shortened life span.

In the study, the researchers developed a “cocktail” of inhibitors in aged Alzheimer-like mice that moderately inhibited both beta-secretase and gamma-secretase enzymes. The technique appeared to reduce the production of amyloid plaque in the brains of the mice—without the adverse side-effects.

“These models allowed us to test whether a greater efficacy can be achieved when both enzymes are modestly reduced in aged Alzheimer-like mice,” said Wong.

Clinical trials testing the efficacy of this combination therapy in human Alzheimer’s patients are on the horizon.

Science Translational Medicine, the newest journal from Science, focuses on outstanding science with promise to improve human health and quality-of-life. Under the direction of Chief Scientific Advisor and former director of the National Institutes of Health Elias Zerhouni and Editor Katrina Kelner, the journal aims to publish groundbreaking research from basic biology that will help make significant advances in medical care, along with commentary on the latest issues in translational medicine.