Dementia Symptoms Have Been Reversed in Mice
There's new hope for patients suffering from dementia. A team of researchers achieved a milestone by reversing the effects of dementia and Alzheimer's disease using a drug.
Researchers from the Lewis Katz School of Medicine at Temple University (LKSOM) displayed the tau pathology reversal using mice -- the first time such a reversal has been documented in an animal model.
Tauopathy refers to a type of neurodegenerative disease, and it's the second most important lesion in the brain in patients suffering from Alzheimer's. Tauopathy is what happens when proteins get tangled after dissociating from microtubules and forming insoluble aggregates of protein.
The study was recently published in the online journal Molecular Neurobiology.
"We show that we can intervene after the disease is established and pharmacologically rescue mice that have tau-induced memory deficits," said senior investigator Domenico Praticò, MD, Research. Pratico also serves as Professor in the Departments of Pharmacology and Microbiology, and Director of the Alzheimer's Center at Temple at LKSOM.
The LKSOM team had its breakthrough when observing leukotrienes -- inflammatory molecules which play a massive role in dementia (particularly in the later stages).
"At the onset of dementia, leukotrienes attempt to protect nerve cells, but over the long term, they cause damage," Praticò explained. "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."
Testing this particular hypothesis proved a bit more challenging than rounding up typical lab mice. Praticò and his colleagues had to used mice specifically engineered with the tau pathology as they aged. The researchers had to then wait until the animals were 12 months old (or the equivalent of 60 years old in humans) before being treated with zileuton. Zileuton inhibits the formation of leukotriene by blocking an enzyme.
The animals underwent 16 weeks of treatment and were then put through a variety of mazes to test their spatial learning memory and their working memory. The mice treated with zileuton performed significantly better than their untreated counterparts. The researchers are linking that superior performance to a reversal of memory deficiency thanks to the zileuton.
The team then analyzed the leukotriene levels in the mice. Those mice who had been treated were found to have a 90 percent reduction in leukotrienes compared to the untreated rodents. There was also a 50 percent lower concentration of insoluble tau -- the protein known to directly damage brain synapses.
"Inflammation was completely gone from tau mice treated with the drug," Praticò said. "The therapy shut down inflammatory processes in the brain, allowing the tau damage to be reversed."
These recent discoveries don't just stop at dementia, according to the researchers. The study noted zileuton is already approved by the US Food and Drug Administration to treat asthma. Advancements in its applications for dementia could improve its applications elsewhere in medicine.
"Leukotrienes are in the lungs and the brain, but we now know that in addition to their functional role in asthma, they also have a functional role in dementia," Praticò said.
"This is an old drug for a new disease," he added. "The research could soon be translated to the clinic, to human patients with Alzheimer's disease."