Alzheimer’s researchers in Philadelphia have successfully reversed cognitive impairments in mice with dementia with the aid of a 20-year-old asthma drug.
The team at Temple University’s Lewis Katz School of Medicine (LKSOM) now hope to fast track clinical trials to verify the results in human subjects. Their work targeted the abnormal accumulation of tau protein inside neurons, which some researchers believe is behind the neurodegeneration that goes along with Alzheimer’s.
“We show that we can intervene after disease is established and pharmacologically rescue mice that have tau-induced memory deficits,” said senior investigator Domenico Praticò, MD, Scott Richards North Star Foundation Chair for Alzheimer’s Research, Professor in the Departments of Pharmacology and Microbiology, and Director of the Alzheimer’s Center at Temple (ACT) at LKSOM.
ACT was established in March 2018 following a gift from Temple University trustee, benefactor and Fox School of Business alum Phil Richards and the Scott Richards North Star Charitable Foundation.
Alzheimer’s disease is the sixth leading cause of death in the United States, with more than five million Americans living with the disease. Dr Praticò – internationally renowned for his work on Alzheimer’s disease, brain health, aging and neurodegeneration – said: “ACT is committed to promoting brain health and fostering discoveries for a better understanding of Alzheimer’s disease and related dementias through cutting-edge research, clinical studies and innovative educational programs. ACT brings together a diverse team of multidisciplinary and talented investigators who devote their entire effort to making a difference in the fight against these diseases.”
The research began by homing in on an inflammatory molecule known as a leukotriene. “At the onset of dementia, leukotrienes attempt to protect nerve cells, but over the long term, they cause damage. 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,” Praticò said.
Specially engineered mice, treated to specifically replicate a degenerative tau pathology that shows the same brain degeneration as a 60-year-old human with early-onset dementia symptoms, were given the asthma drug zileuton, known to inhibit leukotriene formation.
After 16 weeks, the mice treated with zileuton performed significantly better on maze tests to assess their working memory and their spatial learning memory. The treated mice also displayed 90 per cent fewer leukotrienes than their untreated counterparts and 50 per cent less insoluble tau, the protein form thought to damage synapses.
Microscopic examination revealed untreated animals had severe synaptic deterioration, while the synapses of treated tau animals were indistinguishable from those of ordinary mice without the disease. “The therapy shut down inflammatory processes in the brain, allowing the tau damage to be reversed.”
While still in the early stages of research, the explicit reversal of brain damage is a promising breakthrough. Zileuton is already approved by the Food and Drug Administration and has been safely administered to asthma patients for 20 years. Praticò added: “This is an old drug for a new disease. The research could soon be translated to the clinic, to human patients with Alzheimer’s disease.”
Philadelphia is becoming an increasing core of Alzheimer’s research knowledge, also hosting the University of Pennsylvania’s Alzheimer’s Disease Core Center. Greater Philadelphia itself is renowned for its innovation and academic research in the healthcare sector.
(via Temple University, New Atlas, LKSOM)
Featured image: Domenico Praticò, MD, Director of the Alzheimer’s Center at Temple (ACT) at LKSOM.