New Drug Shown to Slow Memory Deficits and Alzheimer's in Mice, Could it Work in Humans?

A drug developed by scientists at the Salk Institute for Biological Studies may be helpful reversing memory deficits and slowing Alzheimer's disease in aged mice following short-term treatment.

"J147 is an exciting new compound because it really has strong potential to be an Alzheimer's disease therapeutic by slowing disease progression and reversing memory deficits following short-term treatment," said lead study author Marguerite Prior, a research associate in Salk's Cellular Neurobiology Laboratory.

Research throughout the years has shown that no disease-modifying drugs for Alzheimer's have proved less than hopeful. Current FDA-approved medications, including Aricept, Razadyne and Exelon, offer only fleeting short-term benefits for Alzheimer's patients, but they do nothing to slow the steady, irreversible decline of brain function that erases a person's memory and ability to think clearly.

According to the Alzheimer's Association, more than 5 million Americans are living with Alzheimer's disease, the sixth leading cause of death in the country and the only one among the top 10 that cannot be prevented, cured or even slowed.

The drug J147 was developed at Salk in the laboratory of David Schubert, a professor in the Cellular Neurobiology Laboratory. He and colleagues bucked the trend within the pharmaceutical industry, which has focused on the biological pathways involved in the formation of amyloid plaques, the dense deposits of protein that characterize the disease. Instead, the Salk team used living neurons grown in laboratory dishes to test whether their new synthetic compounds, which are based upon natural products derived from plants, were effective at protecting brain cells against several pathologies associated with brain aging. From the test results of each chemical iteration of the lead compound, they were able to alter their chemical structures to make them much more potent. Although J147 appears to be safe in mice, the next step will require clinical trials to determine whether the compound will prove safe and effective in humans.

"Alzheimer's disease research has traditionally focused on a single target, the amyloid pathway," said Schubert, "but unfortunately drugs that have been developed through this pathway have not been successful in clinical trials. Our approach is based on the pathologies associated with old age-the greatest risk factor for Alzheimer's and other neurodegenerative diseases-rather than only the specificities of the disease."