— Scientists at Sanford-Burnham Medical Research Institute have discovered a combination of two FDA-approved drugs that appears to stop — and possibly reverse — the destructive changes in the brain caused by Alzheimer’s disease.
By combining two widely used drugs, nitroglycerin and memantine, researchers created a third drug: NitroMemantine. In animal models, the hybrid appears to restore synapses — the connections between neurons — lost in the disease process, according to findings from a 10-year study published last week in the Proceedings of the National Academy of Sciences.
The new experimental drug may be the first to restore brain synapses lost during the progression of Alzheimer’s disease, said Dr. Stuart Lipton, professor and director of Sanford-Burnham’s neuroscience, aging and stem-cell research center, and the study’s lead researcher.
“These findings actually mean that you might be able to intercede not only early but also a bit later,” said Lipton, whose team studied the drug combination in mice and in brain cells derived from human stem cells.
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The new combo drug — developed by researchers at Sanford-Burnham’s La Jolla, Calif., center — is part of an overall effort focused at its Orlando, Fla., sister facility that explores ways scientists can “re-purpose” already approved drugs in new ways to treat disease.
"The potential of drug re-purposing is enormous and will accelerate the pace of drug discovery," said Dr. Steve Gardell, senior director of scientific resources at Sanford-Burnham in Lake Nona.
To get a new drug approved for use in humans is a tremendous accomplishment, he said. Once a drug makes it that far, it should be leveraged for other uses.
Drugs are typically developed for one purpose; however, “observing how they act in humans can open our eyes to other, possibly more valuable, uses,” Gardell said.
Alzheimer’s disease progressively destroys the connections among neurons, leading to memory loss and cognitive decline.
The new research found that when nitroglycerin — commonly used to treat chest pain or angina in patients with coronary heart disease — was added to memantine to form a new drug, the results improved.
It took researchers 37 combinations of the drugs before they found one that worked, Lipton said.
The study was funded by grants from agencies including the National Institutes of Health, the U.S. Department of Defense and the American Heart Association.
Calling the new research “very promising,” Dr. David Smuckler, geriatrician and medical director of Orlando Health’s Center for Aging and Memory Disorder Clinic, said he would welcome a new treatment.
“The medications we have now are not very good. A lot of patients don’t respond, but they’re the best we have,” Smuckler said. “They don’t do much to slow the process, and they definitely don’t reverse it.”