What if a drug to press rewind on the damage Alzheimer’s causes already exists?
That’s what researchers at Temple University asked when they gave a drug called zileuton, an asthma drug, to mice genetically engineered to have Alzheimer’s.
Researchers discovered that the drug was able to remove the build-up of tau, a toxic protein associated with Alzheimer’s that forms into twisted tangles. All brains have tau, but in brains that develop Alzheimer’s, it spreads like an infection in a way that is believed to destroy communication between neurons and cause nerve death.
Not only did the drug remove tau; scientists also found that mice who were given the drug performed better on memory tests.
“We show that we can intervene after disease is established and pharmacologically rescue mice that have tau-induced memory deficits,” said senior study author Domenico Praticò, M.D., Professor in the Departments of Pharmacology and Microbiology at Temple University and Director of the Alzheimer’s Center.
The discovery came after scientists realized that inflammatory molecules called leukotrienes start to act unusually in animals with Alzheimer’s.
“At the onset of dementia, leukotrienes attempt to protect nerve cells, but over the long term, they cause damage,” Praticò said. “Having discovered this, we wanted to know whether blocking leukotrienes could reverse the damage, whether we could do something to fix memory and learning impairments in mice having already abundant tau pathology.”
Blocking leukotrienes in mice led to a 50 percent reduction in tau build-up in their brains. After 16 weeks of treatment, mice were given maze tests to assess their spatial and working memory—two areas that decline in humans with Alzheimer’s. The mice given the drug performed better than those who were not given the drug.
Does this mean that the results can be replicated in humans? While scientists are hopeful, there are a few limitations of the study. These mice did not have beta-amyloid, a protein that accompanies tau and the No. 1 drug target scientists have been trying to nail down in Alzheimer’s for decades. And translating results in mice to humans is usually a long road that takes many years of research to test.
The good news is that the drug is already approved in the U.S. and U.K., meaning if it is found to slow Alzheimer’s in humans in future studies, the approval process would be much shorter than usual. As Praticò put it, “This is an old drug for a new disease.”
This study was published in the journal Molecular Neurobiology.
