Stop dementia in the nose – nasal spray to treat, prevent Alzheimer’s disease

Via repositioning the drug, Osaka City University creates a combination of rifampin and resveratrol and has shown in mouse models that nasal administration improves cognitive function without the negative liver side effects of rifampin only.

Via repositioning the drug, Osaka City University creates a combination of rifampin and resveratrol and has shown in mouse models that nasal administration improves cognitive function without the negative liver side effects of rifampin only.

Dementia is thought to occur when proteins called -amyloid, tau, and -synuclein build up in the brain and form oligomers. A research group from the Department of Translational Neuroscience at Osaka University Graduate School of Medicine had previously shown in a study using mice that the antibiotic rifampicin clears oligomers from the brain and improves cognitive function. However, the drug has been linked with side effects such as liver damage. Resveratrol, an antioxidant found naturally in plants, is used as a supplement in Europe and the United States. “To combat the negative side effects of the existing drug rifampicin, we thought about combining it with the hepatoprotective effects of resveratrol,” says Professor Takami Tomiyama, who acted as principal investigator for the present study.

Anti-dementia collunarium

The combination of the generic drug rifampicin and the food supplement resveratrol, and their intranasal administration with a nasal spray, would provide safer and more effective prophylaxis against dementia. Credit: Takami Tomiyama

This time, the research group administered a fixed-dose combination of rifampin and resveratrol intranasally five days a week for a total of four weeks to model mice from Alzheimer’s disease, frontotemporal dementia and Lewy body dementia, and observed their cognitive functions and brain pathology. The results showed that the combination significantly improved cognitive function in mice, inhibited the accumulation of oligomers, and restored levels of synaptophysin – presynaptic proteins that facilitate synapses. In addition, blood levels of liver enzymes, a marker for liver damage that normally increase with rifampicin, remained normal in the fixed dose combination. In addition, increased levels of expression of brain-derived neurotrophic factor (BDNF) were observed in the hippocampus, which was not observed with rifampicin alone. These results indicate that this fixed dose combination is superior to rifampicin alone in terms of safety and efficacy.

The results of this study have been published online in the Swiss scientific journal Frontiers in neuroscience December 13, 2021.

“The number of patients with dementia has increased all over the world, with some sources predicting the number of patients to double every 20 years. However, there is still no effective treatment for the disease, ”says Tomohiro Umeda, specially appointed speaker and first author of the study. “Recent studies have shown that abnormalities start to appear in the brains of patients with dementia more than 20 years before the onset of the disease. By investigating new therapeutic uses with existing drugs in a process called drug repositioning, the research team hopes to diagnose and prevent dementia before neurons start to die.

Additionally, based on the team’s previous research experience, nasal administration of a fixed-dose combination of rifampicin and resveratrol would increase drug transferability to the brain and further improve safety and medicinal effects. . The dosage used in this study was 0.02 mg rifampicin per mouse per day, or 1 mg / kg / day assuming a mouse weight of 20 g. “Converted to a human dosage based on body surface area, it becomes 0.081 mg / kg / day,” says Prof. Tomiyama, “currently rifampicin is prescribed at 10 mg / kg / day as an antibiotic, and in relation to that, confirmed to us an effect at a much lower dosage.

The development of a fixed-dose combination of rifampicin and resveratrol nasal spray is currently being led by Medilabo RFP, a high-risk company that emerged from the research team’s laboratory. Following the publication of this article, Medilabo RFP began preparations for global clinical trials. In November 2021, with the support of the Japan Foreign Trade Organization (JETRO), Medilabo RFP established a subsidiary in Massachusetts, United States.

Reference: “Oligomer-targeted prevention of neurodegenerative dementia by the intranasal combination of rifampicin and resveratrol – A preclinical study in model mice” by Tomohiro Umeda, Ayumi Sakai, Keiko Shigemori, Ayumi Yokota, Toru Kumagai and Takami Tomiyama, 13 December 2021, Frontiers in neuroscience.
DOI: 10.3389 / fnins.2021.763476

Source link

About Hector Hedgepeth

Hector Hedgepeth

Check Also

Bendigo Health’s Coroanvirus Testing Site in McLaren Street Sees High Test Demand | Bendigo Advertiser

coronavirus, Bendigo Health reminds people to only queue for PCR tests if they have symptoms …