Can a Nasal Spray Prevent Dementia?

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Scientists from Osaka City University are reporting successful preclinical tests of a novel nasal spray designed to prevent the neurodegeneration associated with dementia. The spray combines two inexpensive, pre-existing drugs and was found to improve cognitive function in several different mouse models of dementia.

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The new study from scientists at Osaka City University was published in the journal Frontiers in Neuroscience. It’s a follow-up on from foundational research in 2016 that discovered a common antibiotic called rifampicin can reduce the accumulation of toxic proteins known to be associated with the development of Alzheimer’s disease.

New Atlas’ recent article entitled “Dementia-preventing nasal spray moves to human trials” reports that in a number of mouse experiments, the research indicated the antibiotic could prevent neurodegeneration, if administered in the very earliest stages of disease. However, long-term treatment with rifampicin in humans was not particularly feasible, due to the drug’s occasional adverse effects on the liver.

In 2018, the researchers looked at whether intranasal administration of rifampicin helped deliver the drug more directly to the brain and avoided its damaging side effects on the liver. Those findings promisingly suggested intranasal rifampicin led to higher levels in the brain, improved cognitive outcomes and reductions in liver toxicity.

“To further secure the safety of nasal rifampicin, we hypothesized that rifampicin’s undesired actions could be antagonized by other compounds,” the researchers write in their latest study. “Thus, we explored the literature for a compound that possesses hepatoprotective actions opposite to rifampicin and, if possible, additional clinical effects that rifampicin does not show.”

The new study specifically considered a natural antioxidant called resveratrol, which is found in foods, such as dark chocolate and red wine. This antioxidant has recently been studied for its unique anti-aging and anti-cancer properties. The researchers hypothesized a combination of rifampicin and resveratrol, delivered intranasally, may be the key to a safe long-term treatment that can prevent, or at least slow, the progression of dementia. A fixed-dose rifampicin and resveratrol combination was intranasally administered five times a week for a month to several different mouse models of neurodegeneration, including Alzheimer’s disease and Lewy body dementia. The results showed it improved mouse cognition and blocked the accumulation of toxic proteins in the brain. This combination also showed no signs of liver damage and was more effective at preventing neurodegeneration than delivering each drug by itself.

Takami Tomiyama, lead investigator on the new study, and colleagues have founded a company called Medilabo RFP to start human clinical trials testing the intranasal spray. They should begin soon in Japan and the United States.

Reference: New Atlas (Jan. 3, 2022) “Dementia-preventing nasal spray moves to human trials”